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Hypnosis may relieve pain, cut reliance on morphine at atrial flutter ablation
used as a control, in a small randomized trial.
Ablation is typically performed using conscious sedation and “requires sometimes very high dosages of morphine, and there are sometimes some complications, blood pressure drop, or oxygen desaturation,” Rodrigue Garcia, MD, Poitiers (France) University Hospital, said in an interview.
But patients in the study assigned to undergo hypnosis during the AFlut ablation, performed by practitioners hailing from the French Hypnosis Association, consistently perceived significantly less pain throughout the procedure than those in the active-control group.
They also used almost two-thirds less morphine, which was available to both groups on demand, reported Dr. Garcia, who presented the results of the PAINLESS study at the European Heart Rhythm Association 2020 Virtual Congress. The annual meeting was conducted online this year because of the COVID-19 pandemic.
Hypnotism for pain control may not be widely available in hospitals, “but it’s becoming more and more frequent in the different centers, especially in France,” he said.
The technique is probably also suitable for catheter ablation of ventricular tachycardia, Dr. Garcia said, and “we already use it for atrial fibrillation ablation, because it’s a very common procedure and because, in France, for example, there is a lack of anesthesiologists.” One limitation of hypnosis for such procedures, he said, is that it requires a practitioner with a lot of training and experience.
The current study, “I think, is one of the few, if not the first, randomized trial on this topic, at least for flutter,” Elena Arbelo, MD, PhD, MSc, Hospital Clinic of Barcelona and the University of Barcelona, said in an interview.
“I thought it was very interesting. Many centers have the issue of not having anesthesiology support for their procedures. We have the option of having anesthesiology with us only a few days a week,” said Dr. Arbelo, who was not an investigator with the study.
“If it’s validated in larger cohorts and in different cultures, it may be an interesting way of reducing the need for anesthesiology support, which is a main issue. I know for sure in Europe,” she said, that “some centers do struggle to have anesthesiology support for their EP procedures.”
The single-center trial randomized adults slated to undergo cavotricuspid isthmus ablation (n = 116) for AFlut to receive hypnosis or a control procedure, consisting of nonhypnotic relaxation suggestions and white noise delivered through earphones – 56 and 57 patients, respectively, after exclusion of several who ultimately did not undergo ablation. Any patient could receive 1 mg of morphine if self-reported pain was 5 or greater on a 10-point visual analog scale, or simply on demand.
The hypnosis and control groups were predominantly male and well matched for age (mean, about 69 years in both groups), prevalence of atrial fibrillation, and left ventricular ejection fraction (about 55% for both). Also, in both groups, the procedure duration was approximately 36 minutes.
Asked if all patients in the hypnosis group were actually hypnotized, Dr. Garcia said: “That’s a tricky question” because there was no prespecified definition for successful hypnosis. Between 70% and 80% achieved a hypnotized state, he estimated.
Hypnosis was superior to the control intervention for the primary outcome of pain self-assessment during the ablation procedure, as recorded 45 minutes after ablation. Also, using a 10-point visual analog scale, the hypnosis group rated the average pain intensity as 4.0, whereas the control group rated it as 5.5 (P < .001).
Similarly, instantaneous pain intensity, rated on a 10-point scale every 5 minutes, was lower throughout the procedure for the hypnosis patients than for the control patients (P < .05 at all assessments). Maximum pain intensities, which occurred at the 15- to 25-minute points, were no greater than 3 for hypnosis patients and peaked at approximately 5 for the control patients.
Two of three secondary end points favored the hypnosis group. Morphine consumption averaged 1.3 mg, compared with 3.6 mg for the control group (P < .001). Observer-assessed degrees of sedation were 8.3 and 5.4, respectively, on a 10-point scale (P < .001). And patient self-assessment of anxiety during the procedure was 1.5 in the hypnosis group and 2.5 in the control group on a similar scale.
Regarding morphine use in the two groups, Dr. Garcia said, “It was more than 2 mg of difference, and this can be very important, especially in certain types of patients,” such as those with compromised lung function.
All six complications (11%) observed during the study occurred in the control group. There were four severe hypotensive episodes, one case of oxygen desaturation, and one case of pericardial effusion (P = .03 vs the hypnosis group).
After pointing out the substantial risk for adverse events associated with deep analgesia, particularly from the use of opiates, Paulus Kirchhof, MD, PhD, said, “I think it’s a clinically relevant topic, in the context of reducing the risk of ablation procedures, to try to minimize the use of opiates or other strong anesthetics.”
A multicenter trial could be the next step, said Dr. Kirchhof, from the University Heart and Vascular Center UKE Hamburg (Germany). That would potentially provide “the first evidence for me that this is not sort of something that works in one specific setting, but that it is transferable to other centers, other countries, where practices and complication rates of analgosedation may be different.”
Dr. Kirchhof praised the study design for comparing hypnosis with an active standard-of-care control group. “That is one of the strengths of the study; they tried to design it in a way that didn’t disadvantage the control group.”
The study was funded by the University Hospital of Poitiers. Dr. Garcia and Dr. Arbelo reported no conflicts of interest. Dr. Kirchhof reported support for basic, translational, and clinical research projects from the European Union, the British Heart Foundation, the Leducq Foundation, the Medical Research Council, and the German Centre for Cardiovascular Research, and from several drug and device companies active in atrial fibrillation, from which he received honoraria more than 3 years ago; he is listed as inventor on two patents held by the University of Birmingham (England).
A version of this article originally appeared on Medscape.com.
used as a control, in a small randomized trial.
Ablation is typically performed using conscious sedation and “requires sometimes very high dosages of morphine, and there are sometimes some complications, blood pressure drop, or oxygen desaturation,” Rodrigue Garcia, MD, Poitiers (France) University Hospital, said in an interview.
But patients in the study assigned to undergo hypnosis during the AFlut ablation, performed by practitioners hailing from the French Hypnosis Association, consistently perceived significantly less pain throughout the procedure than those in the active-control group.
They also used almost two-thirds less morphine, which was available to both groups on demand, reported Dr. Garcia, who presented the results of the PAINLESS study at the European Heart Rhythm Association 2020 Virtual Congress. The annual meeting was conducted online this year because of the COVID-19 pandemic.
Hypnotism for pain control may not be widely available in hospitals, “but it’s becoming more and more frequent in the different centers, especially in France,” he said.
The technique is probably also suitable for catheter ablation of ventricular tachycardia, Dr. Garcia said, and “we already use it for atrial fibrillation ablation, because it’s a very common procedure and because, in France, for example, there is a lack of anesthesiologists.” One limitation of hypnosis for such procedures, he said, is that it requires a practitioner with a lot of training and experience.
The current study, “I think, is one of the few, if not the first, randomized trial on this topic, at least for flutter,” Elena Arbelo, MD, PhD, MSc, Hospital Clinic of Barcelona and the University of Barcelona, said in an interview.
“I thought it was very interesting. Many centers have the issue of not having anesthesiology support for their procedures. We have the option of having anesthesiology with us only a few days a week,” said Dr. Arbelo, who was not an investigator with the study.
“If it’s validated in larger cohorts and in different cultures, it may be an interesting way of reducing the need for anesthesiology support, which is a main issue. I know for sure in Europe,” she said, that “some centers do struggle to have anesthesiology support for their EP procedures.”
The single-center trial randomized adults slated to undergo cavotricuspid isthmus ablation (n = 116) for AFlut to receive hypnosis or a control procedure, consisting of nonhypnotic relaxation suggestions and white noise delivered through earphones – 56 and 57 patients, respectively, after exclusion of several who ultimately did not undergo ablation. Any patient could receive 1 mg of morphine if self-reported pain was 5 or greater on a 10-point visual analog scale, or simply on demand.
The hypnosis and control groups were predominantly male and well matched for age (mean, about 69 years in both groups), prevalence of atrial fibrillation, and left ventricular ejection fraction (about 55% for both). Also, in both groups, the procedure duration was approximately 36 minutes.
Asked if all patients in the hypnosis group were actually hypnotized, Dr. Garcia said: “That’s a tricky question” because there was no prespecified definition for successful hypnosis. Between 70% and 80% achieved a hypnotized state, he estimated.
Hypnosis was superior to the control intervention for the primary outcome of pain self-assessment during the ablation procedure, as recorded 45 minutes after ablation. Also, using a 10-point visual analog scale, the hypnosis group rated the average pain intensity as 4.0, whereas the control group rated it as 5.5 (P < .001).
Similarly, instantaneous pain intensity, rated on a 10-point scale every 5 minutes, was lower throughout the procedure for the hypnosis patients than for the control patients (P < .05 at all assessments). Maximum pain intensities, which occurred at the 15- to 25-minute points, were no greater than 3 for hypnosis patients and peaked at approximately 5 for the control patients.
Two of three secondary end points favored the hypnosis group. Morphine consumption averaged 1.3 mg, compared with 3.6 mg for the control group (P < .001). Observer-assessed degrees of sedation were 8.3 and 5.4, respectively, on a 10-point scale (P < .001). And patient self-assessment of anxiety during the procedure was 1.5 in the hypnosis group and 2.5 in the control group on a similar scale.
Regarding morphine use in the two groups, Dr. Garcia said, “It was more than 2 mg of difference, and this can be very important, especially in certain types of patients,” such as those with compromised lung function.
All six complications (11%) observed during the study occurred in the control group. There were four severe hypotensive episodes, one case of oxygen desaturation, and one case of pericardial effusion (P = .03 vs the hypnosis group).
After pointing out the substantial risk for adverse events associated with deep analgesia, particularly from the use of opiates, Paulus Kirchhof, MD, PhD, said, “I think it’s a clinically relevant topic, in the context of reducing the risk of ablation procedures, to try to minimize the use of opiates or other strong anesthetics.”
A multicenter trial could be the next step, said Dr. Kirchhof, from the University Heart and Vascular Center UKE Hamburg (Germany). That would potentially provide “the first evidence for me that this is not sort of something that works in one specific setting, but that it is transferable to other centers, other countries, where practices and complication rates of analgosedation may be different.”
Dr. Kirchhof praised the study design for comparing hypnosis with an active standard-of-care control group. “That is one of the strengths of the study; they tried to design it in a way that didn’t disadvantage the control group.”
The study was funded by the University Hospital of Poitiers. Dr. Garcia and Dr. Arbelo reported no conflicts of interest. Dr. Kirchhof reported support for basic, translational, and clinical research projects from the European Union, the British Heart Foundation, the Leducq Foundation, the Medical Research Council, and the German Centre for Cardiovascular Research, and from several drug and device companies active in atrial fibrillation, from which he received honoraria more than 3 years ago; he is listed as inventor on two patents held by the University of Birmingham (England).
A version of this article originally appeared on Medscape.com.
used as a control, in a small randomized trial.
Ablation is typically performed using conscious sedation and “requires sometimes very high dosages of morphine, and there are sometimes some complications, blood pressure drop, or oxygen desaturation,” Rodrigue Garcia, MD, Poitiers (France) University Hospital, said in an interview.
But patients in the study assigned to undergo hypnosis during the AFlut ablation, performed by practitioners hailing from the French Hypnosis Association, consistently perceived significantly less pain throughout the procedure than those in the active-control group.
They also used almost two-thirds less morphine, which was available to both groups on demand, reported Dr. Garcia, who presented the results of the PAINLESS study at the European Heart Rhythm Association 2020 Virtual Congress. The annual meeting was conducted online this year because of the COVID-19 pandemic.
Hypnotism for pain control may not be widely available in hospitals, “but it’s becoming more and more frequent in the different centers, especially in France,” he said.
The technique is probably also suitable for catheter ablation of ventricular tachycardia, Dr. Garcia said, and “we already use it for atrial fibrillation ablation, because it’s a very common procedure and because, in France, for example, there is a lack of anesthesiologists.” One limitation of hypnosis for such procedures, he said, is that it requires a practitioner with a lot of training and experience.
The current study, “I think, is one of the few, if not the first, randomized trial on this topic, at least for flutter,” Elena Arbelo, MD, PhD, MSc, Hospital Clinic of Barcelona and the University of Barcelona, said in an interview.
“I thought it was very interesting. Many centers have the issue of not having anesthesiology support for their procedures. We have the option of having anesthesiology with us only a few days a week,” said Dr. Arbelo, who was not an investigator with the study.
“If it’s validated in larger cohorts and in different cultures, it may be an interesting way of reducing the need for anesthesiology support, which is a main issue. I know for sure in Europe,” she said, that “some centers do struggle to have anesthesiology support for their EP procedures.”
The single-center trial randomized adults slated to undergo cavotricuspid isthmus ablation (n = 116) for AFlut to receive hypnosis or a control procedure, consisting of nonhypnotic relaxation suggestions and white noise delivered through earphones – 56 and 57 patients, respectively, after exclusion of several who ultimately did not undergo ablation. Any patient could receive 1 mg of morphine if self-reported pain was 5 or greater on a 10-point visual analog scale, or simply on demand.
The hypnosis and control groups were predominantly male and well matched for age (mean, about 69 years in both groups), prevalence of atrial fibrillation, and left ventricular ejection fraction (about 55% for both). Also, in both groups, the procedure duration was approximately 36 minutes.
Asked if all patients in the hypnosis group were actually hypnotized, Dr. Garcia said: “That’s a tricky question” because there was no prespecified definition for successful hypnosis. Between 70% and 80% achieved a hypnotized state, he estimated.
Hypnosis was superior to the control intervention for the primary outcome of pain self-assessment during the ablation procedure, as recorded 45 minutes after ablation. Also, using a 10-point visual analog scale, the hypnosis group rated the average pain intensity as 4.0, whereas the control group rated it as 5.5 (P < .001).
Similarly, instantaneous pain intensity, rated on a 10-point scale every 5 minutes, was lower throughout the procedure for the hypnosis patients than for the control patients (P < .05 at all assessments). Maximum pain intensities, which occurred at the 15- to 25-minute points, were no greater than 3 for hypnosis patients and peaked at approximately 5 for the control patients.
Two of three secondary end points favored the hypnosis group. Morphine consumption averaged 1.3 mg, compared with 3.6 mg for the control group (P < .001). Observer-assessed degrees of sedation were 8.3 and 5.4, respectively, on a 10-point scale (P < .001). And patient self-assessment of anxiety during the procedure was 1.5 in the hypnosis group and 2.5 in the control group on a similar scale.
Regarding morphine use in the two groups, Dr. Garcia said, “It was more than 2 mg of difference, and this can be very important, especially in certain types of patients,” such as those with compromised lung function.
All six complications (11%) observed during the study occurred in the control group. There were four severe hypotensive episodes, one case of oxygen desaturation, and one case of pericardial effusion (P = .03 vs the hypnosis group).
After pointing out the substantial risk for adverse events associated with deep analgesia, particularly from the use of opiates, Paulus Kirchhof, MD, PhD, said, “I think it’s a clinically relevant topic, in the context of reducing the risk of ablation procedures, to try to minimize the use of opiates or other strong anesthetics.”
A multicenter trial could be the next step, said Dr. Kirchhof, from the University Heart and Vascular Center UKE Hamburg (Germany). That would potentially provide “the first evidence for me that this is not sort of something that works in one specific setting, but that it is transferable to other centers, other countries, where practices and complication rates of analgosedation may be different.”
Dr. Kirchhof praised the study design for comparing hypnosis with an active standard-of-care control group. “That is one of the strengths of the study; they tried to design it in a way that didn’t disadvantage the control group.”
The study was funded by the University Hospital of Poitiers. Dr. Garcia and Dr. Arbelo reported no conflicts of interest. Dr. Kirchhof reported support for basic, translational, and clinical research projects from the European Union, the British Heart Foundation, the Leducq Foundation, the Medical Research Council, and the German Centre for Cardiovascular Research, and from several drug and device companies active in atrial fibrillation, from which he received honoraria more than 3 years ago; he is listed as inventor on two patents held by the University of Birmingham (England).
A version of this article originally appeared on Medscape.com.
Brensocatib reduced bronchiectasis exacerbations
Brensocatib, an experimental small-molecule inhibitor targeted to inflammation-regulating neutrophil serine proteases, may be a novel, nonantibiotic option for reducing exacerbations in patients with bronchiectasis, investigators in the phase 2 WILLOW study said.
Among 256 adults with a recent history of bronchiectasis exacerbations, oral brensocatib at doses of both 10 mg and 25 mg daily for 24 weeks was associated with significantly longer time to first exacerbation than placebo, and the 10-mg dose was associated with a significant reduction in the annualized rate of exacerbations, reported James Chalmers, MB, ChB, PhD of Ninewells Hospital and Medical School in Dundee (England).
“We also observed a dose-dependent reduction in neutrophil elastase levels in sputum, which supports the mechanism of action of this drug, and importantly showed a link between reducing neutrophil serine protease activity and clinical benefits in people with bronchiectasis,” he said in at the American Thoracic Society’s virtual clinical trial session.
“This is a very important trial, a landmark trial for people with bronchiectasis, because this is a drug that for the first time appears to be able to target directly neutrophilic inflammation, resulting in clinical benefit,” he said.
Pulmonologist Jennifer L. Taylor-Cousar, MD, MSCS, of National Jewish Health in Denver, who was facilitator for the online presentation but was not involved in the study, said that it offered welcome news.
“For those of us who treat bronchiectasis, a safe and effective anti-inflammatory has really been the Holy Grail, so this is really exciting,” she said.
Novel mechanism of action
Frequent exacerbations in bronchiectasis are related to uncontrolled neutrophilic inflammation, and proinflammatory neutrophil serine proteases (NSPs), including neutrophil elastase, are seen at increased levels in sputum of patients with bronchiectasis. In addition, the presence in sputum of elevated NSPs are associated with exacerbations and poor quality of life, Dr. Chalmers said.
Brensocatib is an inhibitor of dipeptidyl peptidase 1 (DPP1), a lysosomal cysteine protease that is responsible for NSP activation in bone marrow during the neutrophil maturation cycle.
In phase 1 trials, brensocatib was associated with a dose-dependent reduction in neutrophil elastase in healthy volunteers.
Three WILLOW branches
In the phase 2 WILLOW trial, patients with bronchiectasis not related to cystic fibrosis were screened and stratified by Pseudomonas aeruginosa on sputum culture and use of macrolide antibiotics and then randomized in equal proportions to receive either brensocatib at daily oral doses of 25 mg or 10 mg, or placebo for 24 weeks, followed by a 4-week off-treatment period.
Both doses of brensocatib met the primary endpoint of time to first exacerbation, compared with placebo. The hazard ratio (HR) for the 10-mg brensocatib dose, compared with placebo was 0.58 (P = .029), and the HR for the 25-mg dose was 0.62 (P = .046).
The exacerbation rate over 24 weeks among patients on placebo was 48.3%, compared with 31.7% of patients on 10 mg brensocatib (P = .033) and 33.3% of patients on the 25 mg dose (P = .038).
The annualized exacerbation rate was 1.37 for patients on placebo, compared with 0.88 with 10 mg brensocatib (P = .041) and 1.03 with 25 mg brensocatib (nonsignificant).
In both brensocatib groups there were significant reductions from baseline neutrophil elastase concentrations in sputum, compared with placebo (P = .034 for 10 mg and .021 for 25 mg). During the 4-week period following treatment neutrophil elastase levels in both active drug arms rose rapidly and returned to baseline.
The importance of these reductions was reflected in pooled data from the two brensocatib cohorts, which showed that patients who achieved neutrophil elastase levels below the limit of quantification had a significantly lower incidence of bronchiectasis exacerbations (HR 0.28, P < .0001).
Although the study was not powered to compare changes in postbronchodilator forced expiratory volume in 1 second (FEV1) levels, placebo-treated patients had a numerically larger decline in lung function from baseline, compared with brensocatib-treated patients.
Safety
Expected adverse events with brensocatib included those associated with Papillon-Lefèvre syndrome, a rare congenital condition caused by the absence of the gene coding for DPP1, resulting in keratinization leading to redness, thickening of soles and palms, and severe, destructive periodontal disease, as well as reduced immune response to bacterial infection.
Treatment-emergent adverse events (TEAEs) resulting in study discontinuation occurred in only three patients on placebo and 10 mg brensocatib, and four on the 25-mg dose. TEAEs resulting in treatment discontinuation were more common in the placebo arm, occurring in nine patients compared with six each in the brensocatib arms.
Serious TEAEs occurring in more than 3% of patients in any group included infective exacerbations in three patients on placebo, none on the 10-mg dose, and four on the 25-mg dose of brensocatib. Respective numbers of patients with treatment-emergent pneumonia were three, zero, and four.
Other TEAEs included cough, headache, sputum increase, dyspnea, and diarrhea.
Adverse events of special interest included skin events in 10 patients on placebo, 12 on the 10-mg dose, and 21 on the 25-mg brensocatib dose. Dental changes occurred in 3, 13, and 9 patients, and infections in 9, 12, and 14 patients, respectively.
A phase 3 study to confirm efficacy and establish the optimal dose of brensocatib is planned for the end of 2020, “COVID willing,” Dr. Chalmers said.
Dr. Chalmers disclosed consultancy with and research funding from Insmed, which funded the study. Dr. Taylor-Cousar has disclosed grants and/or personal fees from various companies.
Brensocatib, an experimental small-molecule inhibitor targeted to inflammation-regulating neutrophil serine proteases, may be a novel, nonantibiotic option for reducing exacerbations in patients with bronchiectasis, investigators in the phase 2 WILLOW study said.
Among 256 adults with a recent history of bronchiectasis exacerbations, oral brensocatib at doses of both 10 mg and 25 mg daily for 24 weeks was associated with significantly longer time to first exacerbation than placebo, and the 10-mg dose was associated with a significant reduction in the annualized rate of exacerbations, reported James Chalmers, MB, ChB, PhD of Ninewells Hospital and Medical School in Dundee (England).
“We also observed a dose-dependent reduction in neutrophil elastase levels in sputum, which supports the mechanism of action of this drug, and importantly showed a link between reducing neutrophil serine protease activity and clinical benefits in people with bronchiectasis,” he said in at the American Thoracic Society’s virtual clinical trial session.
“This is a very important trial, a landmark trial for people with bronchiectasis, because this is a drug that for the first time appears to be able to target directly neutrophilic inflammation, resulting in clinical benefit,” he said.
Pulmonologist Jennifer L. Taylor-Cousar, MD, MSCS, of National Jewish Health in Denver, who was facilitator for the online presentation but was not involved in the study, said that it offered welcome news.
“For those of us who treat bronchiectasis, a safe and effective anti-inflammatory has really been the Holy Grail, so this is really exciting,” she said.
Novel mechanism of action
Frequent exacerbations in bronchiectasis are related to uncontrolled neutrophilic inflammation, and proinflammatory neutrophil serine proteases (NSPs), including neutrophil elastase, are seen at increased levels in sputum of patients with bronchiectasis. In addition, the presence in sputum of elevated NSPs are associated with exacerbations and poor quality of life, Dr. Chalmers said.
Brensocatib is an inhibitor of dipeptidyl peptidase 1 (DPP1), a lysosomal cysteine protease that is responsible for NSP activation in bone marrow during the neutrophil maturation cycle.
In phase 1 trials, brensocatib was associated with a dose-dependent reduction in neutrophil elastase in healthy volunteers.
Three WILLOW branches
In the phase 2 WILLOW trial, patients with bronchiectasis not related to cystic fibrosis were screened and stratified by Pseudomonas aeruginosa on sputum culture and use of macrolide antibiotics and then randomized in equal proportions to receive either brensocatib at daily oral doses of 25 mg or 10 mg, or placebo for 24 weeks, followed by a 4-week off-treatment period.
Both doses of brensocatib met the primary endpoint of time to first exacerbation, compared with placebo. The hazard ratio (HR) for the 10-mg brensocatib dose, compared with placebo was 0.58 (P = .029), and the HR for the 25-mg dose was 0.62 (P = .046).
The exacerbation rate over 24 weeks among patients on placebo was 48.3%, compared with 31.7% of patients on 10 mg brensocatib (P = .033) and 33.3% of patients on the 25 mg dose (P = .038).
The annualized exacerbation rate was 1.37 for patients on placebo, compared with 0.88 with 10 mg brensocatib (P = .041) and 1.03 with 25 mg brensocatib (nonsignificant).
In both brensocatib groups there were significant reductions from baseline neutrophil elastase concentrations in sputum, compared with placebo (P = .034 for 10 mg and .021 for 25 mg). During the 4-week period following treatment neutrophil elastase levels in both active drug arms rose rapidly and returned to baseline.
The importance of these reductions was reflected in pooled data from the two brensocatib cohorts, which showed that patients who achieved neutrophil elastase levels below the limit of quantification had a significantly lower incidence of bronchiectasis exacerbations (HR 0.28, P < .0001).
Although the study was not powered to compare changes in postbronchodilator forced expiratory volume in 1 second (FEV1) levels, placebo-treated patients had a numerically larger decline in lung function from baseline, compared with brensocatib-treated patients.
Safety
Expected adverse events with brensocatib included those associated with Papillon-Lefèvre syndrome, a rare congenital condition caused by the absence of the gene coding for DPP1, resulting in keratinization leading to redness, thickening of soles and palms, and severe, destructive periodontal disease, as well as reduced immune response to bacterial infection.
Treatment-emergent adverse events (TEAEs) resulting in study discontinuation occurred in only three patients on placebo and 10 mg brensocatib, and four on the 25-mg dose. TEAEs resulting in treatment discontinuation were more common in the placebo arm, occurring in nine patients compared with six each in the brensocatib arms.
Serious TEAEs occurring in more than 3% of patients in any group included infective exacerbations in three patients on placebo, none on the 10-mg dose, and four on the 25-mg dose of brensocatib. Respective numbers of patients with treatment-emergent pneumonia were three, zero, and four.
Other TEAEs included cough, headache, sputum increase, dyspnea, and diarrhea.
Adverse events of special interest included skin events in 10 patients on placebo, 12 on the 10-mg dose, and 21 on the 25-mg brensocatib dose. Dental changes occurred in 3, 13, and 9 patients, and infections in 9, 12, and 14 patients, respectively.
A phase 3 study to confirm efficacy and establish the optimal dose of brensocatib is planned for the end of 2020, “COVID willing,” Dr. Chalmers said.
Dr. Chalmers disclosed consultancy with and research funding from Insmed, which funded the study. Dr. Taylor-Cousar has disclosed grants and/or personal fees from various companies.
Brensocatib, an experimental small-molecule inhibitor targeted to inflammation-regulating neutrophil serine proteases, may be a novel, nonantibiotic option for reducing exacerbations in patients with bronchiectasis, investigators in the phase 2 WILLOW study said.
Among 256 adults with a recent history of bronchiectasis exacerbations, oral brensocatib at doses of both 10 mg and 25 mg daily for 24 weeks was associated with significantly longer time to first exacerbation than placebo, and the 10-mg dose was associated with a significant reduction in the annualized rate of exacerbations, reported James Chalmers, MB, ChB, PhD of Ninewells Hospital and Medical School in Dundee (England).
“We also observed a dose-dependent reduction in neutrophil elastase levels in sputum, which supports the mechanism of action of this drug, and importantly showed a link between reducing neutrophil serine protease activity and clinical benefits in people with bronchiectasis,” he said in at the American Thoracic Society’s virtual clinical trial session.
“This is a very important trial, a landmark trial for people with bronchiectasis, because this is a drug that for the first time appears to be able to target directly neutrophilic inflammation, resulting in clinical benefit,” he said.
Pulmonologist Jennifer L. Taylor-Cousar, MD, MSCS, of National Jewish Health in Denver, who was facilitator for the online presentation but was not involved in the study, said that it offered welcome news.
“For those of us who treat bronchiectasis, a safe and effective anti-inflammatory has really been the Holy Grail, so this is really exciting,” she said.
Novel mechanism of action
Frequent exacerbations in bronchiectasis are related to uncontrolled neutrophilic inflammation, and proinflammatory neutrophil serine proteases (NSPs), including neutrophil elastase, are seen at increased levels in sputum of patients with bronchiectasis. In addition, the presence in sputum of elevated NSPs are associated with exacerbations and poor quality of life, Dr. Chalmers said.
Brensocatib is an inhibitor of dipeptidyl peptidase 1 (DPP1), a lysosomal cysteine protease that is responsible for NSP activation in bone marrow during the neutrophil maturation cycle.
In phase 1 trials, brensocatib was associated with a dose-dependent reduction in neutrophil elastase in healthy volunteers.
Three WILLOW branches
In the phase 2 WILLOW trial, patients with bronchiectasis not related to cystic fibrosis were screened and stratified by Pseudomonas aeruginosa on sputum culture and use of macrolide antibiotics and then randomized in equal proportions to receive either brensocatib at daily oral doses of 25 mg or 10 mg, or placebo for 24 weeks, followed by a 4-week off-treatment period.
Both doses of brensocatib met the primary endpoint of time to first exacerbation, compared with placebo. The hazard ratio (HR) for the 10-mg brensocatib dose, compared with placebo was 0.58 (P = .029), and the HR for the 25-mg dose was 0.62 (P = .046).
The exacerbation rate over 24 weeks among patients on placebo was 48.3%, compared with 31.7% of patients on 10 mg brensocatib (P = .033) and 33.3% of patients on the 25 mg dose (P = .038).
The annualized exacerbation rate was 1.37 for patients on placebo, compared with 0.88 with 10 mg brensocatib (P = .041) and 1.03 with 25 mg brensocatib (nonsignificant).
In both brensocatib groups there were significant reductions from baseline neutrophil elastase concentrations in sputum, compared with placebo (P = .034 for 10 mg and .021 for 25 mg). During the 4-week period following treatment neutrophil elastase levels in both active drug arms rose rapidly and returned to baseline.
The importance of these reductions was reflected in pooled data from the two brensocatib cohorts, which showed that patients who achieved neutrophil elastase levels below the limit of quantification had a significantly lower incidence of bronchiectasis exacerbations (HR 0.28, P < .0001).
Although the study was not powered to compare changes in postbronchodilator forced expiratory volume in 1 second (FEV1) levels, placebo-treated patients had a numerically larger decline in lung function from baseline, compared with brensocatib-treated patients.
Safety
Expected adverse events with brensocatib included those associated with Papillon-Lefèvre syndrome, a rare congenital condition caused by the absence of the gene coding for DPP1, resulting in keratinization leading to redness, thickening of soles and palms, and severe, destructive periodontal disease, as well as reduced immune response to bacterial infection.
Treatment-emergent adverse events (TEAEs) resulting in study discontinuation occurred in only three patients on placebo and 10 mg brensocatib, and four on the 25-mg dose. TEAEs resulting in treatment discontinuation were more common in the placebo arm, occurring in nine patients compared with six each in the brensocatib arms.
Serious TEAEs occurring in more than 3% of patients in any group included infective exacerbations in three patients on placebo, none on the 10-mg dose, and four on the 25-mg dose of brensocatib. Respective numbers of patients with treatment-emergent pneumonia were three, zero, and four.
Other TEAEs included cough, headache, sputum increase, dyspnea, and diarrhea.
Adverse events of special interest included skin events in 10 patients on placebo, 12 on the 10-mg dose, and 21 on the 25-mg brensocatib dose. Dental changes occurred in 3, 13, and 9 patients, and infections in 9, 12, and 14 patients, respectively.
A phase 3 study to confirm efficacy and establish the optimal dose of brensocatib is planned for the end of 2020, “COVID willing,” Dr. Chalmers said.
Dr. Chalmers disclosed consultancy with and research funding from Insmed, which funded the study. Dr. Taylor-Cousar has disclosed grants and/or personal fees from various companies.
FROM ATS 2020
Breast density asymmetry might increase breast cancer risk
The 854 women in the study had been referred for biopsy after an abnormal mammogram.
Researchers used the mammograms to assess global bilateral asymmetry, which was the overall absolute difference in percent fibroglandular tissue volume (%FGV) between the ipsilateral (biopsied) breast and the contralateral (unaffected) breast.
The researchers also assessed local bilateral asymmetry, which was the perilesional %FGV difference in an area twice the size of, but excluding, the biopsy target, and the corresponding area in the unaffected breast.
The women were then divided into quartiles based on breast density asymmetry.
Most of the women had benign breast disease, including proliferative (43%) and nonproliferative (33%) disease, but 23% had carcinoma in situ or invasive breast cancer.
The trend for higher risk of in situ or invasive cancer with increasing breast density asymmetry was observed only in the local analysis. The odds ratio was 1.59 (95% confidence interval, 0.94-2.69) for women in the highest quartile of breast density asymmetry (absolute difference, > 8.23) versus those in the lowest quartile (absolute difference, ≤ –5.55; P = .067).
When compared with women who had proliferative benign disease, women with carcinoma in situ or invasive breast cancer “were more likely to be in the higher than lower quartiles,” said lead investigator Maeve Mullooly, PhD, a research fellow at the Royal College of Surgeons in Dublin.
There was no association between breast density asymmetry and traditional breast cancer risk factors such as age, body mass index, race, and hormone therapy. However, among women diagnosed with benign nonproliferative disease, women with a breast cancer family history were more likely to have higher overall breast density asymmetry.
Study rationale and details
Higher breast density is a known risk factor for breast cancer. Breast asymmetry also has been reported as a possible risk factor (Breast Cancer Res. 2006;8[2]:R14), and incorporation of breast density asymmetry into traditional risk factors in one study improved risk prediction (Breast Cancer Res. 2017 Mar 14;19[1]:29).
Building on that work, the goal of Dr. Mullooly’s study was to “learn how to better use breast density to inform breast cancer risk prediction,” she said.
To that end, her team turned to 854 women enrolled from 2007-2010 in the National Cancer Institute’s Breast Radiology Evaluation and Study of Tissues Project, a cross-sectional molecular epidemiologic study designed to understand how breast density measures are related to breast cancer etiology.
Most of the women were non-Hispanic white. The mean age was 51 years (range, 40-65), and the median body mass index was 25 kg/m2.
About three-quarters of the women (76%) had a breast density asymmetry of at least 2% on the global analysis, with 43% having higher %FGV in the biopsied breast and 33% having higher %FGV in the unaffected breast. In all, 89% of women had local breast density asymmetry, with higher density in the biopsied breast in 61% of women and higher density in the contralateral breast in 28%.
Next steps
This research is ongoing, and additional follow-up is planned, according to Dr. Mullooly. She said the researchers hope to apply more recent analytical techniques to the mammograms and to study the histologic differences in their breast biopsy specimens, among other steps, to see if stronger relationships with greater clinical utility emerge.
It was a “very well done study” with “very provocative data,” said presentation moderator Jennifer Wargo, MD, professor of genomic medicine and surgical oncology at the University of Texas MD Anderson Cancer Center in Houston.
She was interested in the planned next steps, particularly the histologic analysis of dense versus less dense breast tissue. There could be “differences in stroma or hormonal levels even at the microenvironmental level” that “represent a potential field defect, which later puts someone at risk,” she said, adding that it’s “great” that the work is continuing.
The National Cancer Institute funded the research. Dr. Mullooly reported no relevant disclosures. Dr. Wargo disclosed relationships with Bristol-Myers Squibb, Roche/Genentech, Novartis, GlaxoSmithKline, AstraZeneca, Imedex, Dava Oncology, Omniprex, Illumina, Gilead, PeerView, Physician Education Resource, MedImmune, Merck, Biothera Pharmaceuticals, and Microbiome DX.
SOURCE: Mullooly M et al. AACR 2020, Abstract NG15.
The 854 women in the study had been referred for biopsy after an abnormal mammogram.
Researchers used the mammograms to assess global bilateral asymmetry, which was the overall absolute difference in percent fibroglandular tissue volume (%FGV) between the ipsilateral (biopsied) breast and the contralateral (unaffected) breast.
The researchers also assessed local bilateral asymmetry, which was the perilesional %FGV difference in an area twice the size of, but excluding, the biopsy target, and the corresponding area in the unaffected breast.
The women were then divided into quartiles based on breast density asymmetry.
Most of the women had benign breast disease, including proliferative (43%) and nonproliferative (33%) disease, but 23% had carcinoma in situ or invasive breast cancer.
The trend for higher risk of in situ or invasive cancer with increasing breast density asymmetry was observed only in the local analysis. The odds ratio was 1.59 (95% confidence interval, 0.94-2.69) for women in the highest quartile of breast density asymmetry (absolute difference, > 8.23) versus those in the lowest quartile (absolute difference, ≤ –5.55; P = .067).
When compared with women who had proliferative benign disease, women with carcinoma in situ or invasive breast cancer “were more likely to be in the higher than lower quartiles,” said lead investigator Maeve Mullooly, PhD, a research fellow at the Royal College of Surgeons in Dublin.
There was no association between breast density asymmetry and traditional breast cancer risk factors such as age, body mass index, race, and hormone therapy. However, among women diagnosed with benign nonproliferative disease, women with a breast cancer family history were more likely to have higher overall breast density asymmetry.
Study rationale and details
Higher breast density is a known risk factor for breast cancer. Breast asymmetry also has been reported as a possible risk factor (Breast Cancer Res. 2006;8[2]:R14), and incorporation of breast density asymmetry into traditional risk factors in one study improved risk prediction (Breast Cancer Res. 2017 Mar 14;19[1]:29).
Building on that work, the goal of Dr. Mullooly’s study was to “learn how to better use breast density to inform breast cancer risk prediction,” she said.
To that end, her team turned to 854 women enrolled from 2007-2010 in the National Cancer Institute’s Breast Radiology Evaluation and Study of Tissues Project, a cross-sectional molecular epidemiologic study designed to understand how breast density measures are related to breast cancer etiology.
Most of the women were non-Hispanic white. The mean age was 51 years (range, 40-65), and the median body mass index was 25 kg/m2.
About three-quarters of the women (76%) had a breast density asymmetry of at least 2% on the global analysis, with 43% having higher %FGV in the biopsied breast and 33% having higher %FGV in the unaffected breast. In all, 89% of women had local breast density asymmetry, with higher density in the biopsied breast in 61% of women and higher density in the contralateral breast in 28%.
Next steps
This research is ongoing, and additional follow-up is planned, according to Dr. Mullooly. She said the researchers hope to apply more recent analytical techniques to the mammograms and to study the histologic differences in their breast biopsy specimens, among other steps, to see if stronger relationships with greater clinical utility emerge.
It was a “very well done study” with “very provocative data,” said presentation moderator Jennifer Wargo, MD, professor of genomic medicine and surgical oncology at the University of Texas MD Anderson Cancer Center in Houston.
She was interested in the planned next steps, particularly the histologic analysis of dense versus less dense breast tissue. There could be “differences in stroma or hormonal levels even at the microenvironmental level” that “represent a potential field defect, which later puts someone at risk,” she said, adding that it’s “great” that the work is continuing.
The National Cancer Institute funded the research. Dr. Mullooly reported no relevant disclosures. Dr. Wargo disclosed relationships with Bristol-Myers Squibb, Roche/Genentech, Novartis, GlaxoSmithKline, AstraZeneca, Imedex, Dava Oncology, Omniprex, Illumina, Gilead, PeerView, Physician Education Resource, MedImmune, Merck, Biothera Pharmaceuticals, and Microbiome DX.
SOURCE: Mullooly M et al. AACR 2020, Abstract NG15.
The 854 women in the study had been referred for biopsy after an abnormal mammogram.
Researchers used the mammograms to assess global bilateral asymmetry, which was the overall absolute difference in percent fibroglandular tissue volume (%FGV) between the ipsilateral (biopsied) breast and the contralateral (unaffected) breast.
The researchers also assessed local bilateral asymmetry, which was the perilesional %FGV difference in an area twice the size of, but excluding, the biopsy target, and the corresponding area in the unaffected breast.
The women were then divided into quartiles based on breast density asymmetry.
Most of the women had benign breast disease, including proliferative (43%) and nonproliferative (33%) disease, but 23% had carcinoma in situ or invasive breast cancer.
The trend for higher risk of in situ or invasive cancer with increasing breast density asymmetry was observed only in the local analysis. The odds ratio was 1.59 (95% confidence interval, 0.94-2.69) for women in the highest quartile of breast density asymmetry (absolute difference, > 8.23) versus those in the lowest quartile (absolute difference, ≤ –5.55; P = .067).
When compared with women who had proliferative benign disease, women with carcinoma in situ or invasive breast cancer “were more likely to be in the higher than lower quartiles,” said lead investigator Maeve Mullooly, PhD, a research fellow at the Royal College of Surgeons in Dublin.
There was no association between breast density asymmetry and traditional breast cancer risk factors such as age, body mass index, race, and hormone therapy. However, among women diagnosed with benign nonproliferative disease, women with a breast cancer family history were more likely to have higher overall breast density asymmetry.
Study rationale and details
Higher breast density is a known risk factor for breast cancer. Breast asymmetry also has been reported as a possible risk factor (Breast Cancer Res. 2006;8[2]:R14), and incorporation of breast density asymmetry into traditional risk factors in one study improved risk prediction (Breast Cancer Res. 2017 Mar 14;19[1]:29).
Building on that work, the goal of Dr. Mullooly’s study was to “learn how to better use breast density to inform breast cancer risk prediction,” she said.
To that end, her team turned to 854 women enrolled from 2007-2010 in the National Cancer Institute’s Breast Radiology Evaluation and Study of Tissues Project, a cross-sectional molecular epidemiologic study designed to understand how breast density measures are related to breast cancer etiology.
Most of the women were non-Hispanic white. The mean age was 51 years (range, 40-65), and the median body mass index was 25 kg/m2.
About three-quarters of the women (76%) had a breast density asymmetry of at least 2% on the global analysis, with 43% having higher %FGV in the biopsied breast and 33% having higher %FGV in the unaffected breast. In all, 89% of women had local breast density asymmetry, with higher density in the biopsied breast in 61% of women and higher density in the contralateral breast in 28%.
Next steps
This research is ongoing, and additional follow-up is planned, according to Dr. Mullooly. She said the researchers hope to apply more recent analytical techniques to the mammograms and to study the histologic differences in their breast biopsy specimens, among other steps, to see if stronger relationships with greater clinical utility emerge.
It was a “very well done study” with “very provocative data,” said presentation moderator Jennifer Wargo, MD, professor of genomic medicine and surgical oncology at the University of Texas MD Anderson Cancer Center in Houston.
She was interested in the planned next steps, particularly the histologic analysis of dense versus less dense breast tissue. There could be “differences in stroma or hormonal levels even at the microenvironmental level” that “represent a potential field defect, which later puts someone at risk,” she said, adding that it’s “great” that the work is continuing.
The National Cancer Institute funded the research. Dr. Mullooly reported no relevant disclosures. Dr. Wargo disclosed relationships with Bristol-Myers Squibb, Roche/Genentech, Novartis, GlaxoSmithKline, AstraZeneca, Imedex, Dava Oncology, Omniprex, Illumina, Gilead, PeerView, Physician Education Resource, MedImmune, Merck, Biothera Pharmaceuticals, and Microbiome DX.
SOURCE: Mullooly M et al. AACR 2020, Abstract NG15.
FROM AACR 2020
Neural tube defect risk from dolutegravir drops as clinical experience grows
The newest data, based on 3,591 deliveries among women in Botswana infected by HIV and treated with dolutegravir at the time of conception during a little more than 5.5 years through April 2020, showed that dolutegravir use at conception linked with 7 cases of neonatal neural tube defects (NTDs), a 0.19% rate that exceeded comparator rates by about 1 in every 1,000 deliveries, far below the 0.94% rate initially found and that raised a red flag 2 years ago (New Engl J Med. 2018 Sep 6;379[10]:979-81). “The prevalence of NTDs among infants born to women on dolutegravir at conception may be stabilizing at approximately 2 per 1,000,” said Rebecca Zash, MD, during the virtual meeting of the International AIDS conference.
“This small absolute risk for neural tube defects is far outweighed by the potential benefits from dolutegravir” for better tolerability than alternative drugs and fewer drug-drug interactions. “This should allow for broader use of dolutegravir in women,” added Dr. Zash, an HIV specialist at Beth Israel Deaconess Medical Center and codirector of the Placental Scientific Working Group of the Harvard University Center for AIDS Research, both in Boston.
“What this has taught us is that women are not a niche population” of people infected with HIV, but rather constitute about half of HIV patients worldwide. “Maintaining gender equity in HIV treatment requires safety data for treatments during pregnancy,” she said during a press briefing.
The new findings mean that it’s “time to lay to rest” concerns about neural tube defects (NTDs) in infants born to women treated with dolutegravir, “given the incredible benefits of dolutegravir,” commented Monica Gandhi, MD, professor of medicine and associate chief of the division of HIV, infectious disease, and global medicine at the University of California, San Francisco. Another benefit from removing any caveats about use of dolutegravir in women who could become pregnant is that it would simplify treatment recommendations and make dolutegravir the unqualified first-line agent for treating HIV infection, Dr. Gandhi said during the briefing. “It’s super reassuring to have these data, as the incidence of NTDs goes down and down,” she added.
Following the alarm raised by initial findings from the Tsepamo study in 2018, Dr. Zash and associates first updated their data through March 2019, when they reported a revised cumulative NTD incidence rate of 0.3% (New Engl J Med. 2019 Aug 29;381[9]:827-40). The Tsepamo study began by following the pregnancy outcomes of women at eight Botswana sites during August 2014–July 2018, representing 45% of the country’s deliveries. This expanded to 18 sites and 72% of deliveries during July-September 2018, and then starting in September 2019 the scope slightly reduced to 16 Botswana sites with 70% of the nation’s deliveries.
Folate supplementation to women who might conceive is vital, but remains spotty in Botswana. “Folate supplementation is a no-brainer, but has had really slow adoption in many countries,” Dr. Zash said. “Folate supplementation, especially in food so that everyone gets it, will reduce NTDs by half.” The two most recent cases of infants born with a NTD to mothers who had been on dolutegravir at conception occurred in mothers who had received no folate supplementation, Dr. Zash reported.
The most recent HIV treatment guidelines for adults from the Department of Health & Human Services, which date from late 2019, designated dolutegravir plus lamivudine as a first-line regimen for most, but flagged it as an “alternative” antiretroviral drug when treating women who have childbearing potential and are either trying to conceive or are sexually active but not using contraception.
The study had no commercial funding. Dr. Zash has been a researcher in studies funded by CytoDyn, Fulcrum, and Gilead. Dr. Gandhi had no commercial disclosures.
The newest data, based on 3,591 deliveries among women in Botswana infected by HIV and treated with dolutegravir at the time of conception during a little more than 5.5 years through April 2020, showed that dolutegravir use at conception linked with 7 cases of neonatal neural tube defects (NTDs), a 0.19% rate that exceeded comparator rates by about 1 in every 1,000 deliveries, far below the 0.94% rate initially found and that raised a red flag 2 years ago (New Engl J Med. 2018 Sep 6;379[10]:979-81). “The prevalence of NTDs among infants born to women on dolutegravir at conception may be stabilizing at approximately 2 per 1,000,” said Rebecca Zash, MD, during the virtual meeting of the International AIDS conference.
“This small absolute risk for neural tube defects is far outweighed by the potential benefits from dolutegravir” for better tolerability than alternative drugs and fewer drug-drug interactions. “This should allow for broader use of dolutegravir in women,” added Dr. Zash, an HIV specialist at Beth Israel Deaconess Medical Center and codirector of the Placental Scientific Working Group of the Harvard University Center for AIDS Research, both in Boston.
“What this has taught us is that women are not a niche population” of people infected with HIV, but rather constitute about half of HIV patients worldwide. “Maintaining gender equity in HIV treatment requires safety data for treatments during pregnancy,” she said during a press briefing.
The new findings mean that it’s “time to lay to rest” concerns about neural tube defects (NTDs) in infants born to women treated with dolutegravir, “given the incredible benefits of dolutegravir,” commented Monica Gandhi, MD, professor of medicine and associate chief of the division of HIV, infectious disease, and global medicine at the University of California, San Francisco. Another benefit from removing any caveats about use of dolutegravir in women who could become pregnant is that it would simplify treatment recommendations and make dolutegravir the unqualified first-line agent for treating HIV infection, Dr. Gandhi said during the briefing. “It’s super reassuring to have these data, as the incidence of NTDs goes down and down,” she added.
Following the alarm raised by initial findings from the Tsepamo study in 2018, Dr. Zash and associates first updated their data through March 2019, when they reported a revised cumulative NTD incidence rate of 0.3% (New Engl J Med. 2019 Aug 29;381[9]:827-40). The Tsepamo study began by following the pregnancy outcomes of women at eight Botswana sites during August 2014–July 2018, representing 45% of the country’s deliveries. This expanded to 18 sites and 72% of deliveries during July-September 2018, and then starting in September 2019 the scope slightly reduced to 16 Botswana sites with 70% of the nation’s deliveries.
Folate supplementation to women who might conceive is vital, but remains spotty in Botswana. “Folate supplementation is a no-brainer, but has had really slow adoption in many countries,” Dr. Zash said. “Folate supplementation, especially in food so that everyone gets it, will reduce NTDs by half.” The two most recent cases of infants born with a NTD to mothers who had been on dolutegravir at conception occurred in mothers who had received no folate supplementation, Dr. Zash reported.
The most recent HIV treatment guidelines for adults from the Department of Health & Human Services, which date from late 2019, designated dolutegravir plus lamivudine as a first-line regimen for most, but flagged it as an “alternative” antiretroviral drug when treating women who have childbearing potential and are either trying to conceive or are sexually active but not using contraception.
The study had no commercial funding. Dr. Zash has been a researcher in studies funded by CytoDyn, Fulcrum, and Gilead. Dr. Gandhi had no commercial disclosures.
The newest data, based on 3,591 deliveries among women in Botswana infected by HIV and treated with dolutegravir at the time of conception during a little more than 5.5 years through April 2020, showed that dolutegravir use at conception linked with 7 cases of neonatal neural tube defects (NTDs), a 0.19% rate that exceeded comparator rates by about 1 in every 1,000 deliveries, far below the 0.94% rate initially found and that raised a red flag 2 years ago (New Engl J Med. 2018 Sep 6;379[10]:979-81). “The prevalence of NTDs among infants born to women on dolutegravir at conception may be stabilizing at approximately 2 per 1,000,” said Rebecca Zash, MD, during the virtual meeting of the International AIDS conference.
“This small absolute risk for neural tube defects is far outweighed by the potential benefits from dolutegravir” for better tolerability than alternative drugs and fewer drug-drug interactions. “This should allow for broader use of dolutegravir in women,” added Dr. Zash, an HIV specialist at Beth Israel Deaconess Medical Center and codirector of the Placental Scientific Working Group of the Harvard University Center for AIDS Research, both in Boston.
“What this has taught us is that women are not a niche population” of people infected with HIV, but rather constitute about half of HIV patients worldwide. “Maintaining gender equity in HIV treatment requires safety data for treatments during pregnancy,” she said during a press briefing.
The new findings mean that it’s “time to lay to rest” concerns about neural tube defects (NTDs) in infants born to women treated with dolutegravir, “given the incredible benefits of dolutegravir,” commented Monica Gandhi, MD, professor of medicine and associate chief of the division of HIV, infectious disease, and global medicine at the University of California, San Francisco. Another benefit from removing any caveats about use of dolutegravir in women who could become pregnant is that it would simplify treatment recommendations and make dolutegravir the unqualified first-line agent for treating HIV infection, Dr. Gandhi said during the briefing. “It’s super reassuring to have these data, as the incidence of NTDs goes down and down,” she added.
Following the alarm raised by initial findings from the Tsepamo study in 2018, Dr. Zash and associates first updated their data through March 2019, when they reported a revised cumulative NTD incidence rate of 0.3% (New Engl J Med. 2019 Aug 29;381[9]:827-40). The Tsepamo study began by following the pregnancy outcomes of women at eight Botswana sites during August 2014–July 2018, representing 45% of the country’s deliveries. This expanded to 18 sites and 72% of deliveries during July-September 2018, and then starting in September 2019 the scope slightly reduced to 16 Botswana sites with 70% of the nation’s deliveries.
Folate supplementation to women who might conceive is vital, but remains spotty in Botswana. “Folate supplementation is a no-brainer, but has had really slow adoption in many countries,” Dr. Zash said. “Folate supplementation, especially in food so that everyone gets it, will reduce NTDs by half.” The two most recent cases of infants born with a NTD to mothers who had been on dolutegravir at conception occurred in mothers who had received no folate supplementation, Dr. Zash reported.
The most recent HIV treatment guidelines for adults from the Department of Health & Human Services, which date from late 2019, designated dolutegravir plus lamivudine as a first-line regimen for most, but flagged it as an “alternative” antiretroviral drug when treating women who have childbearing potential and are either trying to conceive or are sexually active but not using contraception.
The study had no commercial funding. Dr. Zash has been a researcher in studies funded by CytoDyn, Fulcrum, and Gilead. Dr. Gandhi had no commercial disclosures.
FROM AIDS 2020
Brazilian patient in HIV remission, negative antibody test
A 35-year-old Brazilian man who participated in a trial in which he received an intensified antiretroviral regimen plus supplemental vitamin B3 for 48 weeks has joined the short list of patients who have experienced a period of remission from HIV in the absence of effective treatment.
Along with the Mississippi baby, a San Francisco man, a 24-year-old Thai man, a 9-year-old South African child, and the London and Berlin patients, the Brazilian man has an undetectable viral load and, more than a year after stopping treatment, his HIV antibody test is negative.
But as with the Berlin and London patients, it seems unlikely that – even if the man remains HIV free into the future – the circumstances of his remission will be broadly applicable to other people with HIV, said Carl Dieffenbach, PhD, director of the Division of AIDS at the National Institute of Allergy and Infectious Diseases, National Institutes of Health.
“I don’t think it’s replicable,” Dieffenbach told Medscape Medical News. Researchers should still try to confirm the finding, but they will probably learn more by studying the man’s unique genetic characteristics and immune system “than to go out and treat another 200 people with the same protocol.”
‘Shock-and-kill strategy’
The man had been on treatment since his HIV diagnosis in 2012, and was one of 30 people to enroll in a Brazilian study – the Multi Interventional Study Exploring HIV-1 Residual Replication: A Step Toward HIV Eradication and Sterilizing Cure – in 2016. At that point, his regimen consisted of the combination of efavirenz, lamivudine, and tenofovir disoproxil fumarate (Symfi, Mylan Pharmaceuticals) and his viral load was undetectable.
He was one of five people in the study to be randomized to receive the integrase inhibitor dolutegravir (Tivicay, ViiV Healthcare), the CCR5 receptor inhibitor maraviroc (Selzentry, ViiV Healthcare), and twice-daily nicotinamide 500 mg, a form of vitamin B3, in addition to his regular regimen for 48 weeks.
Nicotinamide has been used for decades because of its anti-infective properties, particularly in tuberculosis. In vitro, it also works to reverse HIV latency, said study investigator Ricardo Diaz, MD, from the Federal University of São Paulo, who presented the data at a press conference for the International AIDS Conference (AIDS) 2020.
“This is a shock-and-kill strategy,” said Leila Giron, PhD, from the Wistar Institute in Philadelphia, who was one of the study investigators. “We did in vitro studies to make sure nicotinamide took HIV out of the cells.”
“The cell machinery changed a lot,” she told Medscape Medical News. “And because it’s a B vitamin, all five participants didn’t have any side effects.”
But the patient was the only person in his treatment group to experience viral load “blips” during treatment – at weeks 16 and 24. And viral DNA was present at low levels in his peripheral blood spots and rectal tissue at baseline and at 48 weeks, and his HIV antibodies dropped from 91.8 RLU at baseline to 58.0 RLU at week 48.
“He had a decline in cell activation, inflammation, and a very deep decline in antibody titers,” Diaz reported.
After 48 weeks of the intensified treatment, the patient returned to his usual regimen for 3 years. Then, in March 2019, he agreed to try an analytical treatment interruption and discontinued all HIV treatment.
“What’s interesting is right before the analytical treatment interruption, the HIV DNA sequences were completely negative,” said Diaz.
Every 3 weeks for the next 64.7 weeks, his viral load came back undetectable, and so did HIV DNA in blood spots. One thing did change, though: in February 2020, the man’s HIV antibody test came back negative.
The team checked that he wasn’t still taking his antiretroviral medication, which might have explained the undetectable viral load, and he wasn’t.
Surprise, skepticism, and hope
The results have prompted surprise, skepticism, and questions from clinicians and researchers.
said Anton Pozniak, MD, from Chelsea and Westminster Hospital in London, who is cochair of AIDS 2020.
“They need a bigger study to see whether or not [the participant] is one of these guys who stopped treatment and might take a year or two, or four, to rebound,” he said. But if other studies replicate the results, the control of HIV in “one in five people would still be huge.”
The rationale behind treatment intensification for HIV remission is that “the three-drug ART regimen was perhaps insufficient to completely block HIV replication” in the reservoirs, even though that replication could be happening below levels detectable with current tests, said Laura Persaud, MD, from the Johns Hopkins University School of Medicine in Baltimore, who is chair of the International Maternal Pediatric Adolescent AIDS Clinical Trial Network (IMPAACT) HIV Cure Committee and was not involved in the study.
“The idea was to see if you could accelerate the decay of the reservoir” if you added medications that targeted different parts of the HIV lifecycle. Symfi, for instance, targets just one step in the viral replication process: the point where HIV RNA reverse transcribes itself into DNA so it can integrate into immune cells. But CCR5 inhibitors block entry of HIV into the cell in the first place, and integrase inhibitors, like raltegravir (Isentress, Merck) and dolutegravir, prevent HIV DNA from integrating into the host chromosome after it has reverse transcribed itself.
Still, recent data suggest that treatment intensification might not be as effective as hypothesized, she said. And the nicotinamide study was in vitro. To what extent this is a direct result of this treatment strategy is unclear.
“It’s hard to believe, in this small study, that this agent [nicotinamide] would have such a striking effect on DNA proviral levels,” she said. “We learn from each of these cases. But this is a single case, with multiple mechanisms that may have contributed to the outcome here. To what extent this is a direct result of this treatment strategy is unclear.”
Only time will tell, and Persaud knows this first hand. Back in 2014, she presented data at another HIV conference on the Mississippi baby who, after 21 months of no treatment, still didn›t have an HIV viral load.
At the time, the baby was hailed as “functionally cured,” but just 6 months later, the virus returned.
Dieffenbach agrees. “There are 10,000 genetic variations that need to be considered, and it all adds up to a unique individual,” he said of the Brazilian patient. “This one is one person, and it’s still early days.”
Counseling patients on niacin supplementation
Some clinicians are already bracing for the flood of people with HIV now wanting to take, or who are already taking, a niacin supplement because of this case, said Laura Waters, MD, from Mortimer Market Centre in London, who is chair of the British HIV Association.
But nicotinamide is different than nicotinic acid, which is what many people mean when they talk about niacin supplementation, according to data from the Office of Dietary Supplements (ODS) at the National Institutes of Health. Nicotinic acid has been used as a supplement for people with high cholesterol for years. Most Americans get more than the recommended daily intake of both types of niacin – 16 mg for adult men and 14 mg for adult women – in their regular diet, according to the 2015/16 National Health and Nutrition Examination Survey.
The Brazilian patient received a total daily dose of nicotinamide of 1000 mg, which is not associated with any adverse effects. Doses above 3000 mg daily can lead to diarrhea and a decrease in platelet count, according to the ODS.
Although Diaz said he doesn’t think people with HIV should run out and start taking a supplement right away, Waters said she sees it as inevitable.
The good news is that if people really are taking nicotinamide – not nicotinic acid – it seems “fairly well tolerated without many side effects,” she said, but added: “I expect shortages of nicotinamide from tomorrow.”
This story first appeared on Medscape.com.
A 35-year-old Brazilian man who participated in a trial in which he received an intensified antiretroviral regimen plus supplemental vitamin B3 for 48 weeks has joined the short list of patients who have experienced a period of remission from HIV in the absence of effective treatment.
Along with the Mississippi baby, a San Francisco man, a 24-year-old Thai man, a 9-year-old South African child, and the London and Berlin patients, the Brazilian man has an undetectable viral load and, more than a year after stopping treatment, his HIV antibody test is negative.
But as with the Berlin and London patients, it seems unlikely that – even if the man remains HIV free into the future – the circumstances of his remission will be broadly applicable to other people with HIV, said Carl Dieffenbach, PhD, director of the Division of AIDS at the National Institute of Allergy and Infectious Diseases, National Institutes of Health.
“I don’t think it’s replicable,” Dieffenbach told Medscape Medical News. Researchers should still try to confirm the finding, but they will probably learn more by studying the man’s unique genetic characteristics and immune system “than to go out and treat another 200 people with the same protocol.”
‘Shock-and-kill strategy’
The man had been on treatment since his HIV diagnosis in 2012, and was one of 30 people to enroll in a Brazilian study – the Multi Interventional Study Exploring HIV-1 Residual Replication: A Step Toward HIV Eradication and Sterilizing Cure – in 2016. At that point, his regimen consisted of the combination of efavirenz, lamivudine, and tenofovir disoproxil fumarate (Symfi, Mylan Pharmaceuticals) and his viral load was undetectable.
He was one of five people in the study to be randomized to receive the integrase inhibitor dolutegravir (Tivicay, ViiV Healthcare), the CCR5 receptor inhibitor maraviroc (Selzentry, ViiV Healthcare), and twice-daily nicotinamide 500 mg, a form of vitamin B3, in addition to his regular regimen for 48 weeks.
Nicotinamide has been used for decades because of its anti-infective properties, particularly in tuberculosis. In vitro, it also works to reverse HIV latency, said study investigator Ricardo Diaz, MD, from the Federal University of São Paulo, who presented the data at a press conference for the International AIDS Conference (AIDS) 2020.
“This is a shock-and-kill strategy,” said Leila Giron, PhD, from the Wistar Institute in Philadelphia, who was one of the study investigators. “We did in vitro studies to make sure nicotinamide took HIV out of the cells.”
“The cell machinery changed a lot,” she told Medscape Medical News. “And because it’s a B vitamin, all five participants didn’t have any side effects.”
But the patient was the only person in his treatment group to experience viral load “blips” during treatment – at weeks 16 and 24. And viral DNA was present at low levels in his peripheral blood spots and rectal tissue at baseline and at 48 weeks, and his HIV antibodies dropped from 91.8 RLU at baseline to 58.0 RLU at week 48.
“He had a decline in cell activation, inflammation, and a very deep decline in antibody titers,” Diaz reported.
After 48 weeks of the intensified treatment, the patient returned to his usual regimen for 3 years. Then, in March 2019, he agreed to try an analytical treatment interruption and discontinued all HIV treatment.
“What’s interesting is right before the analytical treatment interruption, the HIV DNA sequences were completely negative,” said Diaz.
Every 3 weeks for the next 64.7 weeks, his viral load came back undetectable, and so did HIV DNA in blood spots. One thing did change, though: in February 2020, the man’s HIV antibody test came back negative.
The team checked that he wasn’t still taking his antiretroviral medication, which might have explained the undetectable viral load, and he wasn’t.
Surprise, skepticism, and hope
The results have prompted surprise, skepticism, and questions from clinicians and researchers.
said Anton Pozniak, MD, from Chelsea and Westminster Hospital in London, who is cochair of AIDS 2020.
“They need a bigger study to see whether or not [the participant] is one of these guys who stopped treatment and might take a year or two, or four, to rebound,” he said. But if other studies replicate the results, the control of HIV in “one in five people would still be huge.”
The rationale behind treatment intensification for HIV remission is that “the three-drug ART regimen was perhaps insufficient to completely block HIV replication” in the reservoirs, even though that replication could be happening below levels detectable with current tests, said Laura Persaud, MD, from the Johns Hopkins University School of Medicine in Baltimore, who is chair of the International Maternal Pediatric Adolescent AIDS Clinical Trial Network (IMPAACT) HIV Cure Committee and was not involved in the study.
“The idea was to see if you could accelerate the decay of the reservoir” if you added medications that targeted different parts of the HIV lifecycle. Symfi, for instance, targets just one step in the viral replication process: the point where HIV RNA reverse transcribes itself into DNA so it can integrate into immune cells. But CCR5 inhibitors block entry of HIV into the cell in the first place, and integrase inhibitors, like raltegravir (Isentress, Merck) and dolutegravir, prevent HIV DNA from integrating into the host chromosome after it has reverse transcribed itself.
Still, recent data suggest that treatment intensification might not be as effective as hypothesized, she said. And the nicotinamide study was in vitro. To what extent this is a direct result of this treatment strategy is unclear.
“It’s hard to believe, in this small study, that this agent [nicotinamide] would have such a striking effect on DNA proviral levels,” she said. “We learn from each of these cases. But this is a single case, with multiple mechanisms that may have contributed to the outcome here. To what extent this is a direct result of this treatment strategy is unclear.”
Only time will tell, and Persaud knows this first hand. Back in 2014, she presented data at another HIV conference on the Mississippi baby who, after 21 months of no treatment, still didn›t have an HIV viral load.
At the time, the baby was hailed as “functionally cured,” but just 6 months later, the virus returned.
Dieffenbach agrees. “There are 10,000 genetic variations that need to be considered, and it all adds up to a unique individual,” he said of the Brazilian patient. “This one is one person, and it’s still early days.”
Counseling patients on niacin supplementation
Some clinicians are already bracing for the flood of people with HIV now wanting to take, or who are already taking, a niacin supplement because of this case, said Laura Waters, MD, from Mortimer Market Centre in London, who is chair of the British HIV Association.
But nicotinamide is different than nicotinic acid, which is what many people mean when they talk about niacin supplementation, according to data from the Office of Dietary Supplements (ODS) at the National Institutes of Health. Nicotinic acid has been used as a supplement for people with high cholesterol for years. Most Americans get more than the recommended daily intake of both types of niacin – 16 mg for adult men and 14 mg for adult women – in their regular diet, according to the 2015/16 National Health and Nutrition Examination Survey.
The Brazilian patient received a total daily dose of nicotinamide of 1000 mg, which is not associated with any adverse effects. Doses above 3000 mg daily can lead to diarrhea and a decrease in platelet count, according to the ODS.
Although Diaz said he doesn’t think people with HIV should run out and start taking a supplement right away, Waters said she sees it as inevitable.
The good news is that if people really are taking nicotinamide – not nicotinic acid – it seems “fairly well tolerated without many side effects,” she said, but added: “I expect shortages of nicotinamide from tomorrow.”
This story first appeared on Medscape.com.
A 35-year-old Brazilian man who participated in a trial in which he received an intensified antiretroviral regimen plus supplemental vitamin B3 for 48 weeks has joined the short list of patients who have experienced a period of remission from HIV in the absence of effective treatment.
Along with the Mississippi baby, a San Francisco man, a 24-year-old Thai man, a 9-year-old South African child, and the London and Berlin patients, the Brazilian man has an undetectable viral load and, more than a year after stopping treatment, his HIV antibody test is negative.
But as with the Berlin and London patients, it seems unlikely that – even if the man remains HIV free into the future – the circumstances of his remission will be broadly applicable to other people with HIV, said Carl Dieffenbach, PhD, director of the Division of AIDS at the National Institute of Allergy and Infectious Diseases, National Institutes of Health.
“I don’t think it’s replicable,” Dieffenbach told Medscape Medical News. Researchers should still try to confirm the finding, but they will probably learn more by studying the man’s unique genetic characteristics and immune system “than to go out and treat another 200 people with the same protocol.”
‘Shock-and-kill strategy’
The man had been on treatment since his HIV diagnosis in 2012, and was one of 30 people to enroll in a Brazilian study – the Multi Interventional Study Exploring HIV-1 Residual Replication: A Step Toward HIV Eradication and Sterilizing Cure – in 2016. At that point, his regimen consisted of the combination of efavirenz, lamivudine, and tenofovir disoproxil fumarate (Symfi, Mylan Pharmaceuticals) and his viral load was undetectable.
He was one of five people in the study to be randomized to receive the integrase inhibitor dolutegravir (Tivicay, ViiV Healthcare), the CCR5 receptor inhibitor maraviroc (Selzentry, ViiV Healthcare), and twice-daily nicotinamide 500 mg, a form of vitamin B3, in addition to his regular regimen for 48 weeks.
Nicotinamide has been used for decades because of its anti-infective properties, particularly in tuberculosis. In vitro, it also works to reverse HIV latency, said study investigator Ricardo Diaz, MD, from the Federal University of São Paulo, who presented the data at a press conference for the International AIDS Conference (AIDS) 2020.
“This is a shock-and-kill strategy,” said Leila Giron, PhD, from the Wistar Institute in Philadelphia, who was one of the study investigators. “We did in vitro studies to make sure nicotinamide took HIV out of the cells.”
“The cell machinery changed a lot,” she told Medscape Medical News. “And because it’s a B vitamin, all five participants didn’t have any side effects.”
But the patient was the only person in his treatment group to experience viral load “blips” during treatment – at weeks 16 and 24. And viral DNA was present at low levels in his peripheral blood spots and rectal tissue at baseline and at 48 weeks, and his HIV antibodies dropped from 91.8 RLU at baseline to 58.0 RLU at week 48.
“He had a decline in cell activation, inflammation, and a very deep decline in antibody titers,” Diaz reported.
After 48 weeks of the intensified treatment, the patient returned to his usual regimen for 3 years. Then, in March 2019, he agreed to try an analytical treatment interruption and discontinued all HIV treatment.
“What’s interesting is right before the analytical treatment interruption, the HIV DNA sequences were completely negative,” said Diaz.
Every 3 weeks for the next 64.7 weeks, his viral load came back undetectable, and so did HIV DNA in blood spots. One thing did change, though: in February 2020, the man’s HIV antibody test came back negative.
The team checked that he wasn’t still taking his antiretroviral medication, which might have explained the undetectable viral load, and he wasn’t.
Surprise, skepticism, and hope
The results have prompted surprise, skepticism, and questions from clinicians and researchers.
said Anton Pozniak, MD, from Chelsea and Westminster Hospital in London, who is cochair of AIDS 2020.
“They need a bigger study to see whether or not [the participant] is one of these guys who stopped treatment and might take a year or two, or four, to rebound,” he said. But if other studies replicate the results, the control of HIV in “one in five people would still be huge.”
The rationale behind treatment intensification for HIV remission is that “the three-drug ART regimen was perhaps insufficient to completely block HIV replication” in the reservoirs, even though that replication could be happening below levels detectable with current tests, said Laura Persaud, MD, from the Johns Hopkins University School of Medicine in Baltimore, who is chair of the International Maternal Pediatric Adolescent AIDS Clinical Trial Network (IMPAACT) HIV Cure Committee and was not involved in the study.
“The idea was to see if you could accelerate the decay of the reservoir” if you added medications that targeted different parts of the HIV lifecycle. Symfi, for instance, targets just one step in the viral replication process: the point where HIV RNA reverse transcribes itself into DNA so it can integrate into immune cells. But CCR5 inhibitors block entry of HIV into the cell in the first place, and integrase inhibitors, like raltegravir (Isentress, Merck) and dolutegravir, prevent HIV DNA from integrating into the host chromosome after it has reverse transcribed itself.
Still, recent data suggest that treatment intensification might not be as effective as hypothesized, she said. And the nicotinamide study was in vitro. To what extent this is a direct result of this treatment strategy is unclear.
“It’s hard to believe, in this small study, that this agent [nicotinamide] would have such a striking effect on DNA proviral levels,” she said. “We learn from each of these cases. But this is a single case, with multiple mechanisms that may have contributed to the outcome here. To what extent this is a direct result of this treatment strategy is unclear.”
Only time will tell, and Persaud knows this first hand. Back in 2014, she presented data at another HIV conference on the Mississippi baby who, after 21 months of no treatment, still didn›t have an HIV viral load.
At the time, the baby was hailed as “functionally cured,” but just 6 months later, the virus returned.
Dieffenbach agrees. “There are 10,000 genetic variations that need to be considered, and it all adds up to a unique individual,” he said of the Brazilian patient. “This one is one person, and it’s still early days.”
Counseling patients on niacin supplementation
Some clinicians are already bracing for the flood of people with HIV now wanting to take, or who are already taking, a niacin supplement because of this case, said Laura Waters, MD, from Mortimer Market Centre in London, who is chair of the British HIV Association.
But nicotinamide is different than nicotinic acid, which is what many people mean when they talk about niacin supplementation, according to data from the Office of Dietary Supplements (ODS) at the National Institutes of Health. Nicotinic acid has been used as a supplement for people with high cholesterol for years. Most Americans get more than the recommended daily intake of both types of niacin – 16 mg for adult men and 14 mg for adult women – in their regular diet, according to the 2015/16 National Health and Nutrition Examination Survey.
The Brazilian patient received a total daily dose of nicotinamide of 1000 mg, which is not associated with any adverse effects. Doses above 3000 mg daily can lead to diarrhea and a decrease in platelet count, according to the ODS.
Although Diaz said he doesn’t think people with HIV should run out and start taking a supplement right away, Waters said she sees it as inevitable.
The good news is that if people really are taking nicotinamide – not nicotinic acid – it seems “fairly well tolerated without many side effects,” she said, but added: “I expect shortages of nicotinamide from tomorrow.”
This story first appeared on Medscape.com.
Sorting out the many mimickers of psoriasis
“It has an earlier age of onset, usually in infancy, and can occur with the atopic triad that presents with asthma and seasonal allergies as well,” Israel David “Izzy” Andrews, MD, said at the virtual Pediatric Dermatology 2020: Best Practices and Innovations Conference. “There is typically a very strong family history, as this is an autosomal dominant condition, and it’s far more common than psoriasis. The annual incidence is estimated to be 10%-15% of pediatric patients. It has classic areas of involvement depending on the age of the patient, and lesions are intensely pruritic at all times. There is induration and crust, but it’s important to distinguish crust from scale. Whereas crust is dried exudate, and scale is usually secondary to a hyperproliferation of the skin. Initially, treatments (especially topical) are similar and may also delay the formalized diagnosis of either of the two.”
Another psoriasis mimicker, pityriasis rosea, is thought to be secondary to human herpes virus 6 or 7 infection, said Dr. Andrews, of the department of dermatology at Phoenix Children’s Hospital. It typically appears in the teens and tweens and usually presents as a large herald patch or plaque on the trunk. As the herald patch resolves, smaller lesions will develop on the trunk following skin folds. “It’s rarely symptomatic and it’s very short lived, and clears within 6-12 weeks,” Dr. Andrews noted. “It can present with an inverse pattern involving the face, neck, and groin, but sparing the trunk. This variant, termed inverse pityriasis rosea, can be confused with inverse psoriasis, which has a similar distribution. However, the inverse pattern of pityriasis rosea will still resolve in a similar time frame to its more classic variant.”
Pityriasis lichenoides can also be mistaken for psoriasis. The acute form can present with erythematous, scaly papules and plaques, but lesions are often found in different phases of resolution or healing. “This benign lymphoproliferative skin disorder can be very difficult to distinguish from psoriasis and may require a biopsy to rule in or out,” Dr. Andrews said. “It can last months to years and there are few treatments that are effective. It is typically nonresponsive to topical steroids and other treatments that would be more effective for psoriasis, helping to distinguish the two. It is thought to exist in the spectrum with other lymphoproliferative diseases including cutaneous T-cell lymphoma [CTCL]. However, there are only a few cases in the literature that support a transformation from pityriasis lichenoides to CTCL.”
Seborrheic dermatitis is more common than atopic dermatitis and psoriasis, but it can be mistaken for psoriasis. It is caused by an inflammatory response secondary to overgrowth of Malassezia yeast and has a bimodal age distribution. “Seborrheic dermatitis affects babies, teens, and tweens, and can persist into adulthood,” he said. “Infants with cradle cap usually resolve with moisturization, gentle brushing, and occasional antifungal shampoos.” Petaloid seborrheic dermatitis can predominately involve the face with psoriatic-appearing induration, plaques, and varying degrees of scales. “In skin of color, this can be confused with discoid lupus, sarcoidosis, and psoriasis, occasionally requiring a biopsy to distinguish,” said Dr. Andrews, who is also an assistant professor of pediatrics at the Mayo Clinic College of Medicine and Science in Scottsdale, Ariz.
Another psoriasis mimicker, pityriasis amiantacea, is thought to be a more severe form of seborrheic dermatitis. It presents with concretions of scale around hair follicles that are highly adherent and are sometimes called sebopsoriasis. “It may be associated with cutaneous findings of psoriasis elsewhere, but may also be found with secondarily infected atopic dermatitis and tinea capitis; however, in my clinical experience, it is most often found in isolation,” he said. “There may be a seasonal association with exacerbation in warm temperatures, and treatment often consists of humectants like salicylic acid for loosening scale, topical steroids for inflammation, and gentle combing out of scale.”
Infections can also mimic psoriasis. For example, tinea infections are often misdiagnosed as eczema or psoriasis and treated with topical steroids. “This can lead to tinea incognito, making it harder to diagnose either condition without attention to detail,” Dr. Andrews said. “On the body, look for expanding lesions with more raised peripheral edges, and central flattening, giving a classic annular appearance. It’s also important to inquire about family history and contacts including pets, contact sports/mat sports (think yoga, gymnastics, martial arts), or other contacts with similar rashes.” Work-up typically includes a fungal culture and starting empiric oral antifungal medications. “It is important to be able to distinguish scalp psoriasis from tinea capitis to prevent the more inflammatory form of tinea capitis, kerion (a deeper more symptomatic, painful and purulent dermatitis), which can lead to permanent scarring alopecia,” he said.
Bacterial infections can also mimic psoriasis, specifically nonbullous impetigo and ecthyma, the more ulcerative form of impetigo. The most frequent associations are group A Streptococcus, methicillin-susceptible Staphylococcus aureus and methicillin-resistant S. aureus.
Dr. Andrews closed his presentation by noting that tumor necrosis factor–alpha inhibitor–induced psoriasiform drug eruptions can occur in psoriasis-naive patients or unmask a predilection for psoriasis in patients with Crohn’s disease, juvenile idiopathic arthritis, or other autoinflammatory or autoimmune conditions. “They may improve with continued treatment and resolve with switching treatments,” he said. “Early biopsy in psoriasiform drug eruptions can appear like atopic dermatitis on pathology. When suspecting psoriasis in a pediatric patient, it is important to consider the history and physical exam as well as family history and associated comorbidities. While a biopsy may aide in the work-up, diagnosis can be made clinically.”
Dr. Andrews reported having no financial disclosures.
“It has an earlier age of onset, usually in infancy, and can occur with the atopic triad that presents with asthma and seasonal allergies as well,” Israel David “Izzy” Andrews, MD, said at the virtual Pediatric Dermatology 2020: Best Practices and Innovations Conference. “There is typically a very strong family history, as this is an autosomal dominant condition, and it’s far more common than psoriasis. The annual incidence is estimated to be 10%-15% of pediatric patients. It has classic areas of involvement depending on the age of the patient, and lesions are intensely pruritic at all times. There is induration and crust, but it’s important to distinguish crust from scale. Whereas crust is dried exudate, and scale is usually secondary to a hyperproliferation of the skin. Initially, treatments (especially topical) are similar and may also delay the formalized diagnosis of either of the two.”
Another psoriasis mimicker, pityriasis rosea, is thought to be secondary to human herpes virus 6 or 7 infection, said Dr. Andrews, of the department of dermatology at Phoenix Children’s Hospital. It typically appears in the teens and tweens and usually presents as a large herald patch or plaque on the trunk. As the herald patch resolves, smaller lesions will develop on the trunk following skin folds. “It’s rarely symptomatic and it’s very short lived, and clears within 6-12 weeks,” Dr. Andrews noted. “It can present with an inverse pattern involving the face, neck, and groin, but sparing the trunk. This variant, termed inverse pityriasis rosea, can be confused with inverse psoriasis, which has a similar distribution. However, the inverse pattern of pityriasis rosea will still resolve in a similar time frame to its more classic variant.”
Pityriasis lichenoides can also be mistaken for psoriasis. The acute form can present with erythematous, scaly papules and plaques, but lesions are often found in different phases of resolution or healing. “This benign lymphoproliferative skin disorder can be very difficult to distinguish from psoriasis and may require a biopsy to rule in or out,” Dr. Andrews said. “It can last months to years and there are few treatments that are effective. It is typically nonresponsive to topical steroids and other treatments that would be more effective for psoriasis, helping to distinguish the two. It is thought to exist in the spectrum with other lymphoproliferative diseases including cutaneous T-cell lymphoma [CTCL]. However, there are only a few cases in the literature that support a transformation from pityriasis lichenoides to CTCL.”
Seborrheic dermatitis is more common than atopic dermatitis and psoriasis, but it can be mistaken for psoriasis. It is caused by an inflammatory response secondary to overgrowth of Malassezia yeast and has a bimodal age distribution. “Seborrheic dermatitis affects babies, teens, and tweens, and can persist into adulthood,” he said. “Infants with cradle cap usually resolve with moisturization, gentle brushing, and occasional antifungal shampoos.” Petaloid seborrheic dermatitis can predominately involve the face with psoriatic-appearing induration, plaques, and varying degrees of scales. “In skin of color, this can be confused with discoid lupus, sarcoidosis, and psoriasis, occasionally requiring a biopsy to distinguish,” said Dr. Andrews, who is also an assistant professor of pediatrics at the Mayo Clinic College of Medicine and Science in Scottsdale, Ariz.
Another psoriasis mimicker, pityriasis amiantacea, is thought to be a more severe form of seborrheic dermatitis. It presents with concretions of scale around hair follicles that are highly adherent and are sometimes called sebopsoriasis. “It may be associated with cutaneous findings of psoriasis elsewhere, but may also be found with secondarily infected atopic dermatitis and tinea capitis; however, in my clinical experience, it is most often found in isolation,” he said. “There may be a seasonal association with exacerbation in warm temperatures, and treatment often consists of humectants like salicylic acid for loosening scale, topical steroids for inflammation, and gentle combing out of scale.”
Infections can also mimic psoriasis. For example, tinea infections are often misdiagnosed as eczema or psoriasis and treated with topical steroids. “This can lead to tinea incognito, making it harder to diagnose either condition without attention to detail,” Dr. Andrews said. “On the body, look for expanding lesions with more raised peripheral edges, and central flattening, giving a classic annular appearance. It’s also important to inquire about family history and contacts including pets, contact sports/mat sports (think yoga, gymnastics, martial arts), or other contacts with similar rashes.” Work-up typically includes a fungal culture and starting empiric oral antifungal medications. “It is important to be able to distinguish scalp psoriasis from tinea capitis to prevent the more inflammatory form of tinea capitis, kerion (a deeper more symptomatic, painful and purulent dermatitis), which can lead to permanent scarring alopecia,” he said.
Bacterial infections can also mimic psoriasis, specifically nonbullous impetigo and ecthyma, the more ulcerative form of impetigo. The most frequent associations are group A Streptococcus, methicillin-susceptible Staphylococcus aureus and methicillin-resistant S. aureus.
Dr. Andrews closed his presentation by noting that tumor necrosis factor–alpha inhibitor–induced psoriasiform drug eruptions can occur in psoriasis-naive patients or unmask a predilection for psoriasis in patients with Crohn’s disease, juvenile idiopathic arthritis, or other autoinflammatory or autoimmune conditions. “They may improve with continued treatment and resolve with switching treatments,” he said. “Early biopsy in psoriasiform drug eruptions can appear like atopic dermatitis on pathology. When suspecting psoriasis in a pediatric patient, it is important to consider the history and physical exam as well as family history and associated comorbidities. While a biopsy may aide in the work-up, diagnosis can be made clinically.”
Dr. Andrews reported having no financial disclosures.
“It has an earlier age of onset, usually in infancy, and can occur with the atopic triad that presents with asthma and seasonal allergies as well,” Israel David “Izzy” Andrews, MD, said at the virtual Pediatric Dermatology 2020: Best Practices and Innovations Conference. “There is typically a very strong family history, as this is an autosomal dominant condition, and it’s far more common than psoriasis. The annual incidence is estimated to be 10%-15% of pediatric patients. It has classic areas of involvement depending on the age of the patient, and lesions are intensely pruritic at all times. There is induration and crust, but it’s important to distinguish crust from scale. Whereas crust is dried exudate, and scale is usually secondary to a hyperproliferation of the skin. Initially, treatments (especially topical) are similar and may also delay the formalized diagnosis of either of the two.”
Another psoriasis mimicker, pityriasis rosea, is thought to be secondary to human herpes virus 6 or 7 infection, said Dr. Andrews, of the department of dermatology at Phoenix Children’s Hospital. It typically appears in the teens and tweens and usually presents as a large herald patch or plaque on the trunk. As the herald patch resolves, smaller lesions will develop on the trunk following skin folds. “It’s rarely symptomatic and it’s very short lived, and clears within 6-12 weeks,” Dr. Andrews noted. “It can present with an inverse pattern involving the face, neck, and groin, but sparing the trunk. This variant, termed inverse pityriasis rosea, can be confused with inverse psoriasis, which has a similar distribution. However, the inverse pattern of pityriasis rosea will still resolve in a similar time frame to its more classic variant.”
Pityriasis lichenoides can also be mistaken for psoriasis. The acute form can present with erythematous, scaly papules and plaques, but lesions are often found in different phases of resolution or healing. “This benign lymphoproliferative skin disorder can be very difficult to distinguish from psoriasis and may require a biopsy to rule in or out,” Dr. Andrews said. “It can last months to years and there are few treatments that are effective. It is typically nonresponsive to topical steroids and other treatments that would be more effective for psoriasis, helping to distinguish the two. It is thought to exist in the spectrum with other lymphoproliferative diseases including cutaneous T-cell lymphoma [CTCL]. However, there are only a few cases in the literature that support a transformation from pityriasis lichenoides to CTCL.”
Seborrheic dermatitis is more common than atopic dermatitis and psoriasis, but it can be mistaken for psoriasis. It is caused by an inflammatory response secondary to overgrowth of Malassezia yeast and has a bimodal age distribution. “Seborrheic dermatitis affects babies, teens, and tweens, and can persist into adulthood,” he said. “Infants with cradle cap usually resolve with moisturization, gentle brushing, and occasional antifungal shampoos.” Petaloid seborrheic dermatitis can predominately involve the face with psoriatic-appearing induration, plaques, and varying degrees of scales. “In skin of color, this can be confused with discoid lupus, sarcoidosis, and psoriasis, occasionally requiring a biopsy to distinguish,” said Dr. Andrews, who is also an assistant professor of pediatrics at the Mayo Clinic College of Medicine and Science in Scottsdale, Ariz.
Another psoriasis mimicker, pityriasis amiantacea, is thought to be a more severe form of seborrheic dermatitis. It presents with concretions of scale around hair follicles that are highly adherent and are sometimes called sebopsoriasis. “It may be associated with cutaneous findings of psoriasis elsewhere, but may also be found with secondarily infected atopic dermatitis and tinea capitis; however, in my clinical experience, it is most often found in isolation,” he said. “There may be a seasonal association with exacerbation in warm temperatures, and treatment often consists of humectants like salicylic acid for loosening scale, topical steroids for inflammation, and gentle combing out of scale.”
Infections can also mimic psoriasis. For example, tinea infections are often misdiagnosed as eczema or psoriasis and treated with topical steroids. “This can lead to tinea incognito, making it harder to diagnose either condition without attention to detail,” Dr. Andrews said. “On the body, look for expanding lesions with more raised peripheral edges, and central flattening, giving a classic annular appearance. It’s also important to inquire about family history and contacts including pets, contact sports/mat sports (think yoga, gymnastics, martial arts), or other contacts with similar rashes.” Work-up typically includes a fungal culture and starting empiric oral antifungal medications. “It is important to be able to distinguish scalp psoriasis from tinea capitis to prevent the more inflammatory form of tinea capitis, kerion (a deeper more symptomatic, painful and purulent dermatitis), which can lead to permanent scarring alopecia,” he said.
Bacterial infections can also mimic psoriasis, specifically nonbullous impetigo and ecthyma, the more ulcerative form of impetigo. The most frequent associations are group A Streptococcus, methicillin-susceptible Staphylococcus aureus and methicillin-resistant S. aureus.
Dr. Andrews closed his presentation by noting that tumor necrosis factor–alpha inhibitor–induced psoriasiform drug eruptions can occur in psoriasis-naive patients or unmask a predilection for psoriasis in patients with Crohn’s disease, juvenile idiopathic arthritis, or other autoinflammatory or autoimmune conditions. “They may improve with continued treatment and resolve with switching treatments,” he said. “Early biopsy in psoriasiform drug eruptions can appear like atopic dermatitis on pathology. When suspecting psoriasis in a pediatric patient, it is important to consider the history and physical exam as well as family history and associated comorbidities. While a biopsy may aide in the work-up, diagnosis can be made clinically.”
Dr. Andrews reported having no financial disclosures.
FROM PEDIATRIC DERMATOLOGY 2020
Entrectinib results emphasize need for NTRK detection
Although fusions in the neurotrophic receptor tyrosine kinase (NTRK) gene are rare in gastrointestinal carcinomas (found in fewer than 5% of cases), they should be looked for, inasmuch as treatment with the TRK inhibitor entrectinib (Rozlytrek, Genentech/Roche) can achieve robust and durable responses, say researchers.
This point was made during several presentations at the virtual World Conference on Gastrointestinal Cancer (WCGC) 2020 on July 1.
Entrectinib and similar agents that act on NTRK fusion genes are described as tumor agnostic, in that they are biomarkers that define the cancer rather than the organ of origin.
The Food and Drug Administration last year granted accelerated approval of entrectinib for patients with locally advanced or metastatic NTRK-expressing solid tumors that have progressed following prior therapies. The drug can also be used as a first-line treatment when there are no effective therapies.
At the meeting, Manish R. Patel, MD, Department of Medicine, University of Minnesota, Minneapolis, and colleagues presented combined results from the ALKA-372-001, STARTRK-1, and STARTRK-2 studies of entrectinib.
They identified 12 gastrointestinal carcinoma patients among 74 adults with locally advanced/metastatic NTRK fusion positive, TRK inhibitor-naive solid tumors who had undergone at least 6 months of follow-up.
Many of these 12 patients had colorectal cancer (58%) or pancreatic cancer (24%).
Treatment with entrectinib elicited an overall response rate of 50%, which consisted entirely of partial responses.
The median duration of response was 12.9 months, which was largely driven by a median duration of response of 15.1 months among colorectal cancer patients, vs 10.0 months among pancreatic cancer patients and 9.3 months in the patient with cholangiocarcinoma.
The median progression-free survival was 7.1 months across the whole cohort. It was 8.0 months for pancreatic cancer patients and 12.0 months for the patient with cholangiocarcinoma.
The median overall survival was 16 months.
Dr. Patel said that this “demonstrates that entrectinib induces durable and clinically meaningful systemic responses in patients with gastrointestinal carcinomas harboring NTRK fusions.”
He noted that entrectinib is “overall very well tolerated, with very few dose interruptions or reductions, and the discontinuation rate was very low.” The majority of adverse events were of grade 1/2. The most common event was change in taste, which occurred in 37.3% of patients. There were no treatment-related deaths.
“The main take-away point from this abstract is that, though they are rare, if we identify patients with NTRK fusions during the course of the disease, we can offer them benefit from entrectinib, and I would argue that ... we should be screening patients for NTRK fusions much more frequently,” Dr. Patel added.
In the second study, a Belgian team performed immunohistochemistry (IHC) analysis followed by next-generation sequencing on archived samples of biliopancreatic cancers to determine the prevalence of NTRK fusions.
They found just one fusion among almost 150 biliary tract cancers and none in nearly 300 pancreatic adenocarcinomas.
Lead author Anne Demols, MD, PhD, Department of Gastroenterology and Gastrointestinal Oncology, CUB Hôpital Erasme, Brussels, Belgium, said the results show that, “consistent” with their low frequency in solid tumors, NTRK gene fusions are “also rare” in biliopancreatic cancers.
“Given this low frequency, testing and identification are of high clinical importance, due to possible treatment with pan-TRK inhibitors,” she said.
She added that a two-step diagnosis is recommended, in that it is both “time saving” and economical, and that next-generation sequencing is “mandatory” to confirm a positive result on IHC.
For discussant Juan W. Valle, MD, professor of medical oncology at the University of Manchester, United Kingdom, the results of the second study reinforce the take-home message of the first.
He said that “two-step diagnosis can preselect patients suitable for next-generation sequencing assay, and what we saw from the previous [study] is that the therapeutic implications make this an important diagnosis.”
Valle noted that there is an “immortal time bias” in the trial analysis, because patients had to be well enough to undergo at least 6 months of follow-up, and that “future work will focus on the best platform to use for known, as well as the identification of new, fusion partners.”
He highlighted the “improved response rate and progression-free survival” achieved with entrectinib among patients with gastrointestinal cancers harboring NTRK fusions, which will benefit patient outcomes.
Pashtoon Kasi, MD, a gastrointestinal oncologist at the University of Iowa Holden Comprehensive Cancer Center, Iowa City, commented on Twitter that, for him, the results were more than just about the impressive response rate but how “brisk, robust, and durable these tend to be.”
In his experience, even patients with stage IV disease who have responded to entrectinib have been able to undergo “secondary ‘curative’ resections.”
The ALKA-372-001, STARTRK-1 and STARTRK-2 studies were sponsored by F. Hoffmann-La Roche. The study by Demols and colleagues was funded by a research grant from Bayer Health. Dr. Patel reports relationships with Nektar Therapeutic, MSD, and Fate Therapeutics. Demols reports relationships with Bayer, Ipsen, Vifor, Servier and Roche. Dr. Valle reports relationships with numerous companies.
This article first appeared on Medscape.com.
Although fusions in the neurotrophic receptor tyrosine kinase (NTRK) gene are rare in gastrointestinal carcinomas (found in fewer than 5% of cases), they should be looked for, inasmuch as treatment with the TRK inhibitor entrectinib (Rozlytrek, Genentech/Roche) can achieve robust and durable responses, say researchers.
This point was made during several presentations at the virtual World Conference on Gastrointestinal Cancer (WCGC) 2020 on July 1.
Entrectinib and similar agents that act on NTRK fusion genes are described as tumor agnostic, in that they are biomarkers that define the cancer rather than the organ of origin.
The Food and Drug Administration last year granted accelerated approval of entrectinib for patients with locally advanced or metastatic NTRK-expressing solid tumors that have progressed following prior therapies. The drug can also be used as a first-line treatment when there are no effective therapies.
At the meeting, Manish R. Patel, MD, Department of Medicine, University of Minnesota, Minneapolis, and colleagues presented combined results from the ALKA-372-001, STARTRK-1, and STARTRK-2 studies of entrectinib.
They identified 12 gastrointestinal carcinoma patients among 74 adults with locally advanced/metastatic NTRK fusion positive, TRK inhibitor-naive solid tumors who had undergone at least 6 months of follow-up.
Many of these 12 patients had colorectal cancer (58%) or pancreatic cancer (24%).
Treatment with entrectinib elicited an overall response rate of 50%, which consisted entirely of partial responses.
The median duration of response was 12.9 months, which was largely driven by a median duration of response of 15.1 months among colorectal cancer patients, vs 10.0 months among pancreatic cancer patients and 9.3 months in the patient with cholangiocarcinoma.
The median progression-free survival was 7.1 months across the whole cohort. It was 8.0 months for pancreatic cancer patients and 12.0 months for the patient with cholangiocarcinoma.
The median overall survival was 16 months.
Dr. Patel said that this “demonstrates that entrectinib induces durable and clinically meaningful systemic responses in patients with gastrointestinal carcinomas harboring NTRK fusions.”
He noted that entrectinib is “overall very well tolerated, with very few dose interruptions or reductions, and the discontinuation rate was very low.” The majority of adverse events were of grade 1/2. The most common event was change in taste, which occurred in 37.3% of patients. There were no treatment-related deaths.
“The main take-away point from this abstract is that, though they are rare, if we identify patients with NTRK fusions during the course of the disease, we can offer them benefit from entrectinib, and I would argue that ... we should be screening patients for NTRK fusions much more frequently,” Dr. Patel added.
In the second study, a Belgian team performed immunohistochemistry (IHC) analysis followed by next-generation sequencing on archived samples of biliopancreatic cancers to determine the prevalence of NTRK fusions.
They found just one fusion among almost 150 biliary tract cancers and none in nearly 300 pancreatic adenocarcinomas.
Lead author Anne Demols, MD, PhD, Department of Gastroenterology and Gastrointestinal Oncology, CUB Hôpital Erasme, Brussels, Belgium, said the results show that, “consistent” with their low frequency in solid tumors, NTRK gene fusions are “also rare” in biliopancreatic cancers.
“Given this low frequency, testing and identification are of high clinical importance, due to possible treatment with pan-TRK inhibitors,” she said.
She added that a two-step diagnosis is recommended, in that it is both “time saving” and economical, and that next-generation sequencing is “mandatory” to confirm a positive result on IHC.
For discussant Juan W. Valle, MD, professor of medical oncology at the University of Manchester, United Kingdom, the results of the second study reinforce the take-home message of the first.
He said that “two-step diagnosis can preselect patients suitable for next-generation sequencing assay, and what we saw from the previous [study] is that the therapeutic implications make this an important diagnosis.”
Valle noted that there is an “immortal time bias” in the trial analysis, because patients had to be well enough to undergo at least 6 months of follow-up, and that “future work will focus on the best platform to use for known, as well as the identification of new, fusion partners.”
He highlighted the “improved response rate and progression-free survival” achieved with entrectinib among patients with gastrointestinal cancers harboring NTRK fusions, which will benefit patient outcomes.
Pashtoon Kasi, MD, a gastrointestinal oncologist at the University of Iowa Holden Comprehensive Cancer Center, Iowa City, commented on Twitter that, for him, the results were more than just about the impressive response rate but how “brisk, robust, and durable these tend to be.”
In his experience, even patients with stage IV disease who have responded to entrectinib have been able to undergo “secondary ‘curative’ resections.”
The ALKA-372-001, STARTRK-1 and STARTRK-2 studies were sponsored by F. Hoffmann-La Roche. The study by Demols and colleagues was funded by a research grant from Bayer Health. Dr. Patel reports relationships with Nektar Therapeutic, MSD, and Fate Therapeutics. Demols reports relationships with Bayer, Ipsen, Vifor, Servier and Roche. Dr. Valle reports relationships with numerous companies.
This article first appeared on Medscape.com.
Although fusions in the neurotrophic receptor tyrosine kinase (NTRK) gene are rare in gastrointestinal carcinomas (found in fewer than 5% of cases), they should be looked for, inasmuch as treatment with the TRK inhibitor entrectinib (Rozlytrek, Genentech/Roche) can achieve robust and durable responses, say researchers.
This point was made during several presentations at the virtual World Conference on Gastrointestinal Cancer (WCGC) 2020 on July 1.
Entrectinib and similar agents that act on NTRK fusion genes are described as tumor agnostic, in that they are biomarkers that define the cancer rather than the organ of origin.
The Food and Drug Administration last year granted accelerated approval of entrectinib for patients with locally advanced or metastatic NTRK-expressing solid tumors that have progressed following prior therapies. The drug can also be used as a first-line treatment when there are no effective therapies.
At the meeting, Manish R. Patel, MD, Department of Medicine, University of Minnesota, Minneapolis, and colleagues presented combined results from the ALKA-372-001, STARTRK-1, and STARTRK-2 studies of entrectinib.
They identified 12 gastrointestinal carcinoma patients among 74 adults with locally advanced/metastatic NTRK fusion positive, TRK inhibitor-naive solid tumors who had undergone at least 6 months of follow-up.
Many of these 12 patients had colorectal cancer (58%) or pancreatic cancer (24%).
Treatment with entrectinib elicited an overall response rate of 50%, which consisted entirely of partial responses.
The median duration of response was 12.9 months, which was largely driven by a median duration of response of 15.1 months among colorectal cancer patients, vs 10.0 months among pancreatic cancer patients and 9.3 months in the patient with cholangiocarcinoma.
The median progression-free survival was 7.1 months across the whole cohort. It was 8.0 months for pancreatic cancer patients and 12.0 months for the patient with cholangiocarcinoma.
The median overall survival was 16 months.
Dr. Patel said that this “demonstrates that entrectinib induces durable and clinically meaningful systemic responses in patients with gastrointestinal carcinomas harboring NTRK fusions.”
He noted that entrectinib is “overall very well tolerated, with very few dose interruptions or reductions, and the discontinuation rate was very low.” The majority of adverse events were of grade 1/2. The most common event was change in taste, which occurred in 37.3% of patients. There were no treatment-related deaths.
“The main take-away point from this abstract is that, though they are rare, if we identify patients with NTRK fusions during the course of the disease, we can offer them benefit from entrectinib, and I would argue that ... we should be screening patients for NTRK fusions much more frequently,” Dr. Patel added.
In the second study, a Belgian team performed immunohistochemistry (IHC) analysis followed by next-generation sequencing on archived samples of biliopancreatic cancers to determine the prevalence of NTRK fusions.
They found just one fusion among almost 150 biliary tract cancers and none in nearly 300 pancreatic adenocarcinomas.
Lead author Anne Demols, MD, PhD, Department of Gastroenterology and Gastrointestinal Oncology, CUB Hôpital Erasme, Brussels, Belgium, said the results show that, “consistent” with their low frequency in solid tumors, NTRK gene fusions are “also rare” in biliopancreatic cancers.
“Given this low frequency, testing and identification are of high clinical importance, due to possible treatment with pan-TRK inhibitors,” she said.
She added that a two-step diagnosis is recommended, in that it is both “time saving” and economical, and that next-generation sequencing is “mandatory” to confirm a positive result on IHC.
For discussant Juan W. Valle, MD, professor of medical oncology at the University of Manchester, United Kingdom, the results of the second study reinforce the take-home message of the first.
He said that “two-step diagnosis can preselect patients suitable for next-generation sequencing assay, and what we saw from the previous [study] is that the therapeutic implications make this an important diagnosis.”
Valle noted that there is an “immortal time bias” in the trial analysis, because patients had to be well enough to undergo at least 6 months of follow-up, and that “future work will focus on the best platform to use for known, as well as the identification of new, fusion partners.”
He highlighted the “improved response rate and progression-free survival” achieved with entrectinib among patients with gastrointestinal cancers harboring NTRK fusions, which will benefit patient outcomes.
Pashtoon Kasi, MD, a gastrointestinal oncologist at the University of Iowa Holden Comprehensive Cancer Center, Iowa City, commented on Twitter that, for him, the results were more than just about the impressive response rate but how “brisk, robust, and durable these tend to be.”
In his experience, even patients with stage IV disease who have responded to entrectinib have been able to undergo “secondary ‘curative’ resections.”
The ALKA-372-001, STARTRK-1 and STARTRK-2 studies were sponsored by F. Hoffmann-La Roche. The study by Demols and colleagues was funded by a research grant from Bayer Health. Dr. Patel reports relationships with Nektar Therapeutic, MSD, and Fate Therapeutics. Demols reports relationships with Bayer, Ipsen, Vifor, Servier and Roche. Dr. Valle reports relationships with numerous companies.
This article first appeared on Medscape.com.
Intermittent fasting ‘not benign’ for patients with diabetes
stress the authors of a new viewpoint published online July 2 in JAMA.
This is because intermittent fasting in patients with type 2 diabetes has only been studied in seven small, short published trials of very different regimens, with limited evidence of benefit. In addition, some concerns arose from these studies.
Weight loss with intermittent fasting appears to be similar to that attained with caloric restriction, but in the case of those with diabetes, the best way to adjust glucose-lowering medicines to reduce the risk of hypoglycemia while practicing intermittent fasting has not been established, and there is potential for such fasting to cause glycemic variability.
The viewpoint’s lead author Benjamin D. Horne, PhD, MStat, MPH, from Intermountain Medical Center, Salt Lake City, and Stanford (Calif.) University, expanded on the issues in a podcast interview with JAMA editor in chief Howard C. Bauchner, MD.
Asked if he would advise intermittent fasting for patients with type 2 diabetes, Dr. Horne replied that he would recommend it, with caveats, “because of the safety issues – some of which are fairly benign for people who are apparently healthy but may be not quite as benign for people with type 2 diabetes.
“Things such as low blood pressure, weakness, headaches, [and] dizziness are considerations,” he continued, but “the big issue” is hypoglycemia, so caloric restriction may be a better choice for some patients with diabetes.
Dr. Horne said he likes to give patients options. “I’ve met quite a number of people who are very behind time-restricted feeding – eating during a 6- to 8-hour window,” he said. “If they are able to stay on it, they tend to really love it.”
The most popular regimen that results in some weight loss is fasting for 24 hours – with or without a 500-calorie meal – on 2 nonconsecutive days a week, the so-called 5:2 diet. And “as someone who’s in cardiovascular research,” Dr. Horne added, “the one that I’m thinking for long term is once-a-week fasting for a 24-hour period.”
Intermittent fasting: Less safe than calorie restriction in diabetes?
Patients who already have diabetes and lose weight benefit from improved glucose, blood pressure, and lipid levels, Dr. Horne and colleagues wrote.
Currently, intermittent fasting is popular in the lay press and on social media with claims of potential benefits for diabetes “that are as yet untested or unproven,” they added. In fact, “whether a patient with type 2 diabetes should engage in intermittent fasting involves a variety of concerns over safety and efficacy.”
Thus, they examined the existing evidence for the health effects and safety of intermittent fasting – defined as time-restricted feeding, or fasting on alternate days or during 1-4 days a week, with only water or also juice and bone broth, or no more than 700 calories allowed on fasting days – in patients with type 2 diabetes.
They found seven published studies of intermittent fasting in patients with type 2 diabetes, including five randomized clinical trials, of which only one study had more than 63 patients.
Intermittent fasting regimens in the studies included five fasting frequencies and most follow-up durations were 4 months or less, including 18-20 hours a day for 2 weeks; 2 days a week for 12 weeks (two studies) or for 12 months (one study); 3-4 days a week for 7-11 months; 4 days a week for 12 weeks; and 17 days in 4 months.
They all reported that intermittent fasting was tied to weight loss, and most (but not all) of the studies also found that it was associated with decreases in A1c and improved glucose levels, quality of life, and blood pressure, but not insulin resistance.
But this “heterogeneity of designs and regimens and the variance in results make it difficult to draw clinically meaningful direction,” Dr. Horne and colleagues observed.
Moreover, only one study addressed the relative safety of two intermittent fasting regimens, and it found that both regimens increased hypoglycemic events despite the use of a medication dose-change protocol.
Only one study explicitly compared intermittent fasting with caloric restriction, which found “that a twice-weekly intermittent fasting regimen improved [A1c] levels is promising,” the authors wrote.
However, that study showed only noninferiority for change in A1c level (–0.3% for intermittent fasting vs. –0.5% for caloric restriction).
The major implication, according to the viewpoint authors, is that “intermittent fasting may be less safe than caloric restriction although approximately equivalently effective.”
“Therefore,” they summarized, “until intermittent fasting is shown to be more effective than caloric restriction for reducing [A1c] or otherwise controlling diabetes, that study – and the limited other high-quality data – suggest that intermittent fasting regimens for patients with type 2 diabetes recommended by health professionals or promoted to the public should be limited to individuals for whom the risk of hypoglycemia is closely monitored and medications are carefully adjusted to ensure safety.”
Should continuous glucose monitoring to detect glycemic variability be considered?
Intermittent fasting may also bring wider fluctuations of glycemic control than simple calorie restriction, with hypoglycemia during fasting times and hyperglycemia during feeding times, which would not be reflected in A1c levels, Dr. Horne and colleagues pointed out.
“Studies have raised concern that glycemic variability leads to both microvascular (e.g., retinopathy) and macrovascular (e.g., coronary disease) complications in patients with type 2 diabetes,” they cautioned.
Therefore, “continuous glucose monitoring should be considered for studies of ... clinical interventions using intermittent fasting in patients with type 2 diabetes,” they concluded.
Dr. Horne has reported serving as principal investigator of grants for studies on intermittent fasting from the Intermountain Research and Medical Foundation. Disclosures of the other two authors are listed with the viewpoint.
A version of this article originally appeared on Medscape.com.
stress the authors of a new viewpoint published online July 2 in JAMA.
This is because intermittent fasting in patients with type 2 diabetes has only been studied in seven small, short published trials of very different regimens, with limited evidence of benefit. In addition, some concerns arose from these studies.
Weight loss with intermittent fasting appears to be similar to that attained with caloric restriction, but in the case of those with diabetes, the best way to adjust glucose-lowering medicines to reduce the risk of hypoglycemia while practicing intermittent fasting has not been established, and there is potential for such fasting to cause glycemic variability.
The viewpoint’s lead author Benjamin D. Horne, PhD, MStat, MPH, from Intermountain Medical Center, Salt Lake City, and Stanford (Calif.) University, expanded on the issues in a podcast interview with JAMA editor in chief Howard C. Bauchner, MD.
Asked if he would advise intermittent fasting for patients with type 2 diabetes, Dr. Horne replied that he would recommend it, with caveats, “because of the safety issues – some of which are fairly benign for people who are apparently healthy but may be not quite as benign for people with type 2 diabetes.
“Things such as low blood pressure, weakness, headaches, [and] dizziness are considerations,” he continued, but “the big issue” is hypoglycemia, so caloric restriction may be a better choice for some patients with diabetes.
Dr. Horne said he likes to give patients options. “I’ve met quite a number of people who are very behind time-restricted feeding – eating during a 6- to 8-hour window,” he said. “If they are able to stay on it, they tend to really love it.”
The most popular regimen that results in some weight loss is fasting for 24 hours – with or without a 500-calorie meal – on 2 nonconsecutive days a week, the so-called 5:2 diet. And “as someone who’s in cardiovascular research,” Dr. Horne added, “the one that I’m thinking for long term is once-a-week fasting for a 24-hour period.”
Intermittent fasting: Less safe than calorie restriction in diabetes?
Patients who already have diabetes and lose weight benefit from improved glucose, blood pressure, and lipid levels, Dr. Horne and colleagues wrote.
Currently, intermittent fasting is popular in the lay press and on social media with claims of potential benefits for diabetes “that are as yet untested or unproven,” they added. In fact, “whether a patient with type 2 diabetes should engage in intermittent fasting involves a variety of concerns over safety and efficacy.”
Thus, they examined the existing evidence for the health effects and safety of intermittent fasting – defined as time-restricted feeding, or fasting on alternate days or during 1-4 days a week, with only water or also juice and bone broth, or no more than 700 calories allowed on fasting days – in patients with type 2 diabetes.
They found seven published studies of intermittent fasting in patients with type 2 diabetes, including five randomized clinical trials, of which only one study had more than 63 patients.
Intermittent fasting regimens in the studies included five fasting frequencies and most follow-up durations were 4 months or less, including 18-20 hours a day for 2 weeks; 2 days a week for 12 weeks (two studies) or for 12 months (one study); 3-4 days a week for 7-11 months; 4 days a week for 12 weeks; and 17 days in 4 months.
They all reported that intermittent fasting was tied to weight loss, and most (but not all) of the studies also found that it was associated with decreases in A1c and improved glucose levels, quality of life, and blood pressure, but not insulin resistance.
But this “heterogeneity of designs and regimens and the variance in results make it difficult to draw clinically meaningful direction,” Dr. Horne and colleagues observed.
Moreover, only one study addressed the relative safety of two intermittent fasting regimens, and it found that both regimens increased hypoglycemic events despite the use of a medication dose-change protocol.
Only one study explicitly compared intermittent fasting with caloric restriction, which found “that a twice-weekly intermittent fasting regimen improved [A1c] levels is promising,” the authors wrote.
However, that study showed only noninferiority for change in A1c level (–0.3% for intermittent fasting vs. –0.5% for caloric restriction).
The major implication, according to the viewpoint authors, is that “intermittent fasting may be less safe than caloric restriction although approximately equivalently effective.”
“Therefore,” they summarized, “until intermittent fasting is shown to be more effective than caloric restriction for reducing [A1c] or otherwise controlling diabetes, that study – and the limited other high-quality data – suggest that intermittent fasting regimens for patients with type 2 diabetes recommended by health professionals or promoted to the public should be limited to individuals for whom the risk of hypoglycemia is closely monitored and medications are carefully adjusted to ensure safety.”
Should continuous glucose monitoring to detect glycemic variability be considered?
Intermittent fasting may also bring wider fluctuations of glycemic control than simple calorie restriction, with hypoglycemia during fasting times and hyperglycemia during feeding times, which would not be reflected in A1c levels, Dr. Horne and colleagues pointed out.
“Studies have raised concern that glycemic variability leads to both microvascular (e.g., retinopathy) and macrovascular (e.g., coronary disease) complications in patients with type 2 diabetes,” they cautioned.
Therefore, “continuous glucose monitoring should be considered for studies of ... clinical interventions using intermittent fasting in patients with type 2 diabetes,” they concluded.
Dr. Horne has reported serving as principal investigator of grants for studies on intermittent fasting from the Intermountain Research and Medical Foundation. Disclosures of the other two authors are listed with the viewpoint.
A version of this article originally appeared on Medscape.com.
stress the authors of a new viewpoint published online July 2 in JAMA.
This is because intermittent fasting in patients with type 2 diabetes has only been studied in seven small, short published trials of very different regimens, with limited evidence of benefit. In addition, some concerns arose from these studies.
Weight loss with intermittent fasting appears to be similar to that attained with caloric restriction, but in the case of those with diabetes, the best way to adjust glucose-lowering medicines to reduce the risk of hypoglycemia while practicing intermittent fasting has not been established, and there is potential for such fasting to cause glycemic variability.
The viewpoint’s lead author Benjamin D. Horne, PhD, MStat, MPH, from Intermountain Medical Center, Salt Lake City, and Stanford (Calif.) University, expanded on the issues in a podcast interview with JAMA editor in chief Howard C. Bauchner, MD.
Asked if he would advise intermittent fasting for patients with type 2 diabetes, Dr. Horne replied that he would recommend it, with caveats, “because of the safety issues – some of which are fairly benign for people who are apparently healthy but may be not quite as benign for people with type 2 diabetes.
“Things such as low blood pressure, weakness, headaches, [and] dizziness are considerations,” he continued, but “the big issue” is hypoglycemia, so caloric restriction may be a better choice for some patients with diabetes.
Dr. Horne said he likes to give patients options. “I’ve met quite a number of people who are very behind time-restricted feeding – eating during a 6- to 8-hour window,” he said. “If they are able to stay on it, they tend to really love it.”
The most popular regimen that results in some weight loss is fasting for 24 hours – with or without a 500-calorie meal – on 2 nonconsecutive days a week, the so-called 5:2 diet. And “as someone who’s in cardiovascular research,” Dr. Horne added, “the one that I’m thinking for long term is once-a-week fasting for a 24-hour period.”
Intermittent fasting: Less safe than calorie restriction in diabetes?
Patients who already have diabetes and lose weight benefit from improved glucose, blood pressure, and lipid levels, Dr. Horne and colleagues wrote.
Currently, intermittent fasting is popular in the lay press and on social media with claims of potential benefits for diabetes “that are as yet untested or unproven,” they added. In fact, “whether a patient with type 2 diabetes should engage in intermittent fasting involves a variety of concerns over safety and efficacy.”
Thus, they examined the existing evidence for the health effects and safety of intermittent fasting – defined as time-restricted feeding, or fasting on alternate days or during 1-4 days a week, with only water or also juice and bone broth, or no more than 700 calories allowed on fasting days – in patients with type 2 diabetes.
They found seven published studies of intermittent fasting in patients with type 2 diabetes, including five randomized clinical trials, of which only one study had more than 63 patients.
Intermittent fasting regimens in the studies included five fasting frequencies and most follow-up durations were 4 months or less, including 18-20 hours a day for 2 weeks; 2 days a week for 12 weeks (two studies) or for 12 months (one study); 3-4 days a week for 7-11 months; 4 days a week for 12 weeks; and 17 days in 4 months.
They all reported that intermittent fasting was tied to weight loss, and most (but not all) of the studies also found that it was associated with decreases in A1c and improved glucose levels, quality of life, and blood pressure, but not insulin resistance.
But this “heterogeneity of designs and regimens and the variance in results make it difficult to draw clinically meaningful direction,” Dr. Horne and colleagues observed.
Moreover, only one study addressed the relative safety of two intermittent fasting regimens, and it found that both regimens increased hypoglycemic events despite the use of a medication dose-change protocol.
Only one study explicitly compared intermittent fasting with caloric restriction, which found “that a twice-weekly intermittent fasting regimen improved [A1c] levels is promising,” the authors wrote.
However, that study showed only noninferiority for change in A1c level (–0.3% for intermittent fasting vs. –0.5% for caloric restriction).
The major implication, according to the viewpoint authors, is that “intermittent fasting may be less safe than caloric restriction although approximately equivalently effective.”
“Therefore,” they summarized, “until intermittent fasting is shown to be more effective than caloric restriction for reducing [A1c] or otherwise controlling diabetes, that study – and the limited other high-quality data – suggest that intermittent fasting regimens for patients with type 2 diabetes recommended by health professionals or promoted to the public should be limited to individuals for whom the risk of hypoglycemia is closely monitored and medications are carefully adjusted to ensure safety.”
Should continuous glucose monitoring to detect glycemic variability be considered?
Intermittent fasting may also bring wider fluctuations of glycemic control than simple calorie restriction, with hypoglycemia during fasting times and hyperglycemia during feeding times, which would not be reflected in A1c levels, Dr. Horne and colleagues pointed out.
“Studies have raised concern that glycemic variability leads to both microvascular (e.g., retinopathy) and macrovascular (e.g., coronary disease) complications in patients with type 2 diabetes,” they cautioned.
Therefore, “continuous glucose monitoring should be considered for studies of ... clinical interventions using intermittent fasting in patients with type 2 diabetes,” they concluded.
Dr. Horne has reported serving as principal investigator of grants for studies on intermittent fasting from the Intermountain Research and Medical Foundation. Disclosures of the other two authors are listed with the viewpoint.
A version of this article originally appeared on Medscape.com.
Holistic HIV care broadens scope to noncommunicable diseases
Several HIV management efforts in African groups have developed differentiated service delivery models for people living with HIV who also have noncommunicable diseases, offering diagnostic and management strategies that can treat HIV patients holistically and address their range of health issues.
These efforts allow “countries with effective HIV programs to leverage lessons learned and best practices to enhance chronic noncommunicable disease” management, Miriam Rabkin, MD, said at the virtual meeting of the International AIDS conference. This approach aims to address the “growing prevalence of chronic noncommunicable diseases in low- and middle-income countries,” and the recognition that ”people living with HIV have the same or higher prevalence” of chronic noncommunicable diseases as that of others in the region where they live, said Dr. Rabkin, an epidemiologist at Columbia University in New York and director for health systems strengthening at ICAP, an international AIDS care program run at Columbia. The differentiated service delivery model derived from the premise that “one size does not fit all,” and that effective interventions must be “tailored” to the social and clinical circumstances of specific regions, she explained.
One program has focused on introducing more contemporary methods for diagnosing leukemias, lymphomas, and melanomas using flow cytometry at the Uganda National Health Laboratory Service in Kampala. This change in testing, which became available to patients starting in February 2019, has allowed diagnostics with fresh specimens that require minimal processing and results returned to referring physicians within 48 hours, a significant upgrade from the 1- to 4-week delay that was typical in the past, said Steven J. Kussick, MD, a hematopathologist and associate medical director of PhenoPath, a commercial pathology laboratory in Seattle.
The idea was to “leverage existing HIV laboratory capabilities to transform cancer diagnosis in sub-Saharan Africa,” he said during his talk at the conference. The flow cytometry approach allows an experienced pathologist like Dr. Kussick to diagnose clearcut cases in “5 seconds,” he said. The lab has already run specimens from more than 200 patients, and estimates an ability to handle specimens from about 250 patients per year at a total annual cost of roughly $60,000, an apparently sustainable operating model, said Dr. Kussick, who serves as a full-time consultant to the operation and was also instrumental in the 5-year process that created the diagnostic program. Future improvements planned for this program include bringing on-line a higher complexity diagnostic assay that’s closer to what is currently standard U.S. testing, digital imaging to facilitate consultation with remote experts, adding immunochemistry assays to allow diagnosis of solid tumors, and opening of a second laboratory in Kenya.
Another noncommunicable disease intervention in Africa that’s building on existing infrastructure for dealing with HIV infection is targeting hypertension, the most lethal risk factor globally for preventable deaths, said Jennifer Cohn, MD, senior vice president for cardiovascular health at the New York–based Resolve to Save Lives initiative. “We need to learn from what’s been done for HIV to rapidly incorporate and scale differentiated service models,” she said.
HIV and hypertension, along with diabetes, “are beginning to be recognized as ‘syndemics,’ ”synergistic pandemics, that need a holistic approach. A recent review of the topic reported that in the seven sub-Saharan countries with the highest HIV infection prevalence the percentage of adults with hypertension ranged from 20% to 24% (Curr Opin HIV AIDS. 2020 Jul;15[4]:356-60). Projections call for a “dramatic” increase in the prevalence of hypertension in both the general population and among people living with HIV, Dr. Cohn said.
As an example of the potential for combining HIV and antihypertensive care into a one-stop protocol, she cited a model program launched at Makarere University in Kampala, Uganda, that integrates HIV and antihypertensive treatment. Recent data from the program showed that among HIV-infected individuals 24% also had hypertension, and while the program lagged in putting only 28% of these hypertensive patients on a blood pressure-lowering regimen, more than three quarters of these patients on treatment successfully reached their goal blood pressure, proving the feasibility of the combined approach, Dr. Cohn said.
“Starting and scaling with differentiated service delivery models for noncommunicable diseases can help overcome barriers to uptake of care,” concluded Dr. Cohn. “As HIV cohorts age, we have to adapt and ensure we are providing quality, holistic care, including care for high impact noncommunicable diseases such as hypertension.”
Dr. Rabkin and Dr. Cohn had no disclosures.
Several HIV management efforts in African groups have developed differentiated service delivery models for people living with HIV who also have noncommunicable diseases, offering diagnostic and management strategies that can treat HIV patients holistically and address their range of health issues.
These efforts allow “countries with effective HIV programs to leverage lessons learned and best practices to enhance chronic noncommunicable disease” management, Miriam Rabkin, MD, said at the virtual meeting of the International AIDS conference. This approach aims to address the “growing prevalence of chronic noncommunicable diseases in low- and middle-income countries,” and the recognition that ”people living with HIV have the same or higher prevalence” of chronic noncommunicable diseases as that of others in the region where they live, said Dr. Rabkin, an epidemiologist at Columbia University in New York and director for health systems strengthening at ICAP, an international AIDS care program run at Columbia. The differentiated service delivery model derived from the premise that “one size does not fit all,” and that effective interventions must be “tailored” to the social and clinical circumstances of specific regions, she explained.
One program has focused on introducing more contemporary methods for diagnosing leukemias, lymphomas, and melanomas using flow cytometry at the Uganda National Health Laboratory Service in Kampala. This change in testing, which became available to patients starting in February 2019, has allowed diagnostics with fresh specimens that require minimal processing and results returned to referring physicians within 48 hours, a significant upgrade from the 1- to 4-week delay that was typical in the past, said Steven J. Kussick, MD, a hematopathologist and associate medical director of PhenoPath, a commercial pathology laboratory in Seattle.
The idea was to “leverage existing HIV laboratory capabilities to transform cancer diagnosis in sub-Saharan Africa,” he said during his talk at the conference. The flow cytometry approach allows an experienced pathologist like Dr. Kussick to diagnose clearcut cases in “5 seconds,” he said. The lab has already run specimens from more than 200 patients, and estimates an ability to handle specimens from about 250 patients per year at a total annual cost of roughly $60,000, an apparently sustainable operating model, said Dr. Kussick, who serves as a full-time consultant to the operation and was also instrumental in the 5-year process that created the diagnostic program. Future improvements planned for this program include bringing on-line a higher complexity diagnostic assay that’s closer to what is currently standard U.S. testing, digital imaging to facilitate consultation with remote experts, adding immunochemistry assays to allow diagnosis of solid tumors, and opening of a second laboratory in Kenya.
Another noncommunicable disease intervention in Africa that’s building on existing infrastructure for dealing with HIV infection is targeting hypertension, the most lethal risk factor globally for preventable deaths, said Jennifer Cohn, MD, senior vice president for cardiovascular health at the New York–based Resolve to Save Lives initiative. “We need to learn from what’s been done for HIV to rapidly incorporate and scale differentiated service models,” she said.
HIV and hypertension, along with diabetes, “are beginning to be recognized as ‘syndemics,’ ”synergistic pandemics, that need a holistic approach. A recent review of the topic reported that in the seven sub-Saharan countries with the highest HIV infection prevalence the percentage of adults with hypertension ranged from 20% to 24% (Curr Opin HIV AIDS. 2020 Jul;15[4]:356-60). Projections call for a “dramatic” increase in the prevalence of hypertension in both the general population and among people living with HIV, Dr. Cohn said.
As an example of the potential for combining HIV and antihypertensive care into a one-stop protocol, she cited a model program launched at Makarere University in Kampala, Uganda, that integrates HIV and antihypertensive treatment. Recent data from the program showed that among HIV-infected individuals 24% also had hypertension, and while the program lagged in putting only 28% of these hypertensive patients on a blood pressure-lowering regimen, more than three quarters of these patients on treatment successfully reached their goal blood pressure, proving the feasibility of the combined approach, Dr. Cohn said.
“Starting and scaling with differentiated service delivery models for noncommunicable diseases can help overcome barriers to uptake of care,” concluded Dr. Cohn. “As HIV cohorts age, we have to adapt and ensure we are providing quality, holistic care, including care for high impact noncommunicable diseases such as hypertension.”
Dr. Rabkin and Dr. Cohn had no disclosures.
Several HIV management efforts in African groups have developed differentiated service delivery models for people living with HIV who also have noncommunicable diseases, offering diagnostic and management strategies that can treat HIV patients holistically and address their range of health issues.
These efforts allow “countries with effective HIV programs to leverage lessons learned and best practices to enhance chronic noncommunicable disease” management, Miriam Rabkin, MD, said at the virtual meeting of the International AIDS conference. This approach aims to address the “growing prevalence of chronic noncommunicable diseases in low- and middle-income countries,” and the recognition that ”people living with HIV have the same or higher prevalence” of chronic noncommunicable diseases as that of others in the region where they live, said Dr. Rabkin, an epidemiologist at Columbia University in New York and director for health systems strengthening at ICAP, an international AIDS care program run at Columbia. The differentiated service delivery model derived from the premise that “one size does not fit all,” and that effective interventions must be “tailored” to the social and clinical circumstances of specific regions, she explained.
One program has focused on introducing more contemporary methods for diagnosing leukemias, lymphomas, and melanomas using flow cytometry at the Uganda National Health Laboratory Service in Kampala. This change in testing, which became available to patients starting in February 2019, has allowed diagnostics with fresh specimens that require minimal processing and results returned to referring physicians within 48 hours, a significant upgrade from the 1- to 4-week delay that was typical in the past, said Steven J. Kussick, MD, a hematopathologist and associate medical director of PhenoPath, a commercial pathology laboratory in Seattle.
The idea was to “leverage existing HIV laboratory capabilities to transform cancer diagnosis in sub-Saharan Africa,” he said during his talk at the conference. The flow cytometry approach allows an experienced pathologist like Dr. Kussick to diagnose clearcut cases in “5 seconds,” he said. The lab has already run specimens from more than 200 patients, and estimates an ability to handle specimens from about 250 patients per year at a total annual cost of roughly $60,000, an apparently sustainable operating model, said Dr. Kussick, who serves as a full-time consultant to the operation and was also instrumental in the 5-year process that created the diagnostic program. Future improvements planned for this program include bringing on-line a higher complexity diagnostic assay that’s closer to what is currently standard U.S. testing, digital imaging to facilitate consultation with remote experts, adding immunochemistry assays to allow diagnosis of solid tumors, and opening of a second laboratory in Kenya.
Another noncommunicable disease intervention in Africa that’s building on existing infrastructure for dealing with HIV infection is targeting hypertension, the most lethal risk factor globally for preventable deaths, said Jennifer Cohn, MD, senior vice president for cardiovascular health at the New York–based Resolve to Save Lives initiative. “We need to learn from what’s been done for HIV to rapidly incorporate and scale differentiated service models,” she said.
HIV and hypertension, along with diabetes, “are beginning to be recognized as ‘syndemics,’ ”synergistic pandemics, that need a holistic approach. A recent review of the topic reported that in the seven sub-Saharan countries with the highest HIV infection prevalence the percentage of adults with hypertension ranged from 20% to 24% (Curr Opin HIV AIDS. 2020 Jul;15[4]:356-60). Projections call for a “dramatic” increase in the prevalence of hypertension in both the general population and among people living with HIV, Dr. Cohn said.
As an example of the potential for combining HIV and antihypertensive care into a one-stop protocol, she cited a model program launched at Makarere University in Kampala, Uganda, that integrates HIV and antihypertensive treatment. Recent data from the program showed that among HIV-infected individuals 24% also had hypertension, and while the program lagged in putting only 28% of these hypertensive patients on a blood pressure-lowering regimen, more than three quarters of these patients on treatment successfully reached their goal blood pressure, proving the feasibility of the combined approach, Dr. Cohn said.
“Starting and scaling with differentiated service delivery models for noncommunicable diseases can help overcome barriers to uptake of care,” concluded Dr. Cohn. “As HIV cohorts age, we have to adapt and ensure we are providing quality, holistic care, including care for high impact noncommunicable diseases such as hypertension.”
Dr. Rabkin and Dr. Cohn had no disclosures.
FROM AIDS 2020
COVID-19 disruptions ‘life threatening’ for people with HIV
When the COVID-19 pandemic led to a blanket shelter-in-place order in California in March, it did more than shut down in-person visits at Ward 86, the HIV clinic for publicly insured patients at San Francisco General Hospital. It also led to a decrease in viral suppression among the clinic›s clients. By the end of June, the percentage of patients with an undetectable viral load had dropped by nearly one-third.
This is exactly what Monica Gandhi, MD, associate division chief of HIV, infectious diseases, and global medicine at the University of California, San Francisco, and medical director of the clinic, was afraid of.
“We’re profoundly worried about the impact of COVID-19 on actual treatment outcomes,” said Dr. Gandhi, cochair of the virtual International AIDS Conference (AIDS) 2020.
And it’s not just the clinic’s clients at risk. Of the 106 countries served by the Global Fund to Fight HIV, Tuberculosis, and Malaria, 85% saw disruptions in HIV programs, according to a report released last month.
These service disruptions are considerable and “life threatening,” affecting some of the people at greatest risk for HIV acquisition and poor outcomes – such as people engaged in transactional sex (40%), men who have sex with men (37%), and transgender people (31%) – the 2020 Global AIDS Update, released today by UNAIDS, reports.
“In sub-Saharan Africa alone, if there is a 6-month interruption in HIV treatment services, it will account for an additional 500,000 deaths. That doubles the number of deaths in sub-Saharan Africa alone and brings us back to 2008 mortality levels,” said Shannon Hader, MD, deputy executive director of UNAIDS. “We just can’t allow that to happen.”
In addition, 73 countries are at risk of running out of HIV medications, according to a World Health Organization report, also released today.
Quantifying the impact
The impact is not the same for all patients, said Anton Pozniak, MD, consulting physician in HIV medicine at the Chelsea and Westminster Hospital in London, and international cochair of AIDS 2020.
For some, COVID-19 has not changed much. Their viral loads remain undetectable and all they need is multimonth supplies of their antiretroviral therapy (ART) medications, he told Medscape Medical News. Still, he said he worries about the well-documented effects that social isolation is having on the mental health of these patients, and the increase in substance use associated with the pandemic.
Then there is a small group of patients with HIV who had put off starting ART before the pandemic, but now want to start, he reported.
And finally, there are the people for whom the fear of COVID-19 has crippled their ability to get care.
There are people who have decided they don’t want to come to the hospital or come to the clinic because they’re scared of getting COVID-19.
“It’s really very striking,” said Dr. Pozniak. “There are people who have decided they don’t want to come to the hospital or come to the clinic because they’re scared of getting COVID-19. We’ve offered to deliver treatment, but they don’t want the stigma of parcels of drugs arriving.”
In a study presented at the conference, four of 12 care and substance-use treatment facilities in Europe and North America – including Seattle and Philadelphia – reported patients taking longer to fill ART prescriptions. And four of the 12 also reported that clients who injected drugs and were at risk for or living with HIV were having trouble adhering to prescribed therapies. In addition, at 11 of the sites, HIV testing has either nearly or completely shut down.
Structural barriers to telemedicine
And then there are structural barriers to care – poverty, lack of transportation, lack of or slow internet access, and lack of insurance – which affect 10% to 20% of the people with HIV that Jodie Dionne-Odom, MD, sees at the 1917 Ryan White HIV clinic at the University of Alabama at Birmingham.
These are the patients she said she worries about most, the ones who, even before COVID-19, were barely managing to pay their rent, car payments, and cell phone bills.
“With COVID-19 and being at home or being laid off, those things could no longer be paid. They’ve lost their phone, they’ve lost their car,” said Dionne-Odom, chief of women’s health services for the clinic. “That’s a really significant impact, because that’s exactly the group you can’t reach by telemedicine.”
In March, when the 1917 Clinic began providing the majority of services online, these people fell off the radar, said Aadia Rana, MD, associate professor of infectious diseases at the University of Alabama at Birmingham, who also works at the clinic.
This is not for lack of trying, she explained. Staff called patients weekly to check in and reschedule appointments, but there were some they just couldn’t reach.
Although the data for the second quarter have not yet been analyzed, “I would expect that our typically close to 90% viral suppression rate is going to decrease,” she said.
This decrease is likely widespread, said Rana, who is principle investigator of the Long-Acting Therapy to Improve Treatment Success in Daily Life (LATITUDE) study.
Many of the 33 sites involved in LATITUDE shut down in the early months of the pandemic, but some are now coming back online. In fact, “we are getting all these pleas from sites around the country saying, ‘Hey, once LATITUDE is open for enrollment, we have so many people who would now be eligible’,” she told Medscape Medical News.
“Why are they now eligible and they weren’t eligible before? I’m assuming it’s because they now have a detectable viral load,” which is one of the requirements for enrollment in LATITUDE, she explained.
Impact on the LGBTI community
At the onset of the COVID-19 pandemic, Erik Lamontagne, senior economist at UNAIDS, wondered how the quarantine was affecting LGBTI people.
To find out, he and his colleagues launched a survey asking just that. He is also coprinciple investigator of the LGBT Happiness Survey, a multicountry survey of LGBTI people launched last year.
The 13,562 LGBTI respondents came from 138 countries or territories. Of the 1,140 respondents living with HIV, 26% had seen their HIV care disrupted or restricted in some way during the pandemic, and 55% of those had no more than a month’s worth of HIV medications on hand.
But the pandemic hasn’t just affected people already living with HIV, Mr. Lamontagne reported. Nine of 10 respondents were living under some form of stay-at-home order, 73% were not meeting their basic needs, 37% had missed meals as a result of economic hardship, and half of those who were still working expected to lose their jobs.
Many could not afford to quarantine, Mr. Lamontagne told Medscape Medical News. And financial resources were stretched so thin that about 1% of respondents reported engaging in transactional sex for the first time. Some reported that their economic circumstances were so dire that they couldn’t require clients to wear condoms, increasing their risk for both COVID-19 and HIV.
“What they can eat in the evening is what they can earn during the day,” Mr. Lamontagne explained.
Unfortunately, it is the people already in a situation of economic vulnerability – often those from the LGBTI community – who are most affected by COVID-19, he added.
PrEP use changing
The pandemic has also affected the use of pre-exposure prophylaxis (PrEP).
South African women taking PrEP to protect themselves from HIV during pregnancy were 2.36 times more likely to miss a clinic visit to refill their prescription after COVID-19 lockdowns began than before, data presented at the conference showed. The women cited fear of acquiring COVID-19 at the medical facility, fear of police, transportation barriers, and long clinic wait times to explain the missed visits.
A study on the use of PrEP at Fenway Health, a sexual health clinic in Boston, showed a 278% increase in unfilled PrEP prescriptions after stay-at-home orders and a 72.1% drop in new PrEP prescriptions.
It’s unclear what these data, which will be presented at the conference later this week, mean, said Douglas Krakower, MD, assistant professor of medicine and population medicine at Harvard Medical School in Boston.
“We don’t know whether this represents people having trouble accessing PrEP” out of concern about getting COVID “or concerns about financial implications,” he explained.
“They may have had hardships from unemployment or other financial constraints” and have lost insurance or are still having to pay copays, he told Medscape Medical News. Or it could just be that they’re not going out or having sex, so they’ve discontinued the medication.
“Anecdotally we’ve heard that some patients are sheltering in place and not having sex and so have chosen not to use PrEP,” he added.
It’s also possible that people are rationing pills or have moved themselves to the PrEP 2-1-1 protocol, which is used only when someone is having sex, said Dr. Krakower, citing a study showing that sexual behavior is continuing as usual during quarantine for about half the gay men in the United States.
Resilience and fragility
It’s not just people living with HIV whose routines have changed during the pandemic. A survey of HIV clinicians around the world conducted by the International Association of Providers of AIDS Care showed that 88% of HIV clinicians have been pulled away from their regular work to manage COVID-19 in their communities.
But the COVID-19 pandemic shows no signs of stopping, and clinicians are now having to re-engage with their HIV patients.
“What COVID-19 has represented for us is a looking glass to see the resilience, but also the fragility, in HIV responses, not just in the global south, but also in the global north,” José Zuniga, PhD, IAPAC president and chief executive officer, said during a preconference session on controlling the HIV epidemic.
For Dr. Dionne-Odom, reopening the 1917 Clinic in Alabama meant tracking down patients who could not participate in telemedicine. Fortunately (or unfortunately, depending on how you look at it), the clinic, which serves a population with a high level of economic insecurity, has worked to get as many phone numbers as possible for each patient. So when the clinic opened back up, staff was able to call family members, friends, and trusted contacts to bring their patients back into the clinic.
“No one wanted to reopen too quickly,” said Dr. Dionne-Odom. “But having people come in allowed us to do all the other things that are the key part of HIV care: getting them connected with a social worker and making sure they have enough food, helping them with their electricity bills and their housing issues, all the wrap-around services that are so crucial for these patients.”
This article first appeared on Medscape.com.
When the COVID-19 pandemic led to a blanket shelter-in-place order in California in March, it did more than shut down in-person visits at Ward 86, the HIV clinic for publicly insured patients at San Francisco General Hospital. It also led to a decrease in viral suppression among the clinic›s clients. By the end of June, the percentage of patients with an undetectable viral load had dropped by nearly one-third.
This is exactly what Monica Gandhi, MD, associate division chief of HIV, infectious diseases, and global medicine at the University of California, San Francisco, and medical director of the clinic, was afraid of.
“We’re profoundly worried about the impact of COVID-19 on actual treatment outcomes,” said Dr. Gandhi, cochair of the virtual International AIDS Conference (AIDS) 2020.
And it’s not just the clinic’s clients at risk. Of the 106 countries served by the Global Fund to Fight HIV, Tuberculosis, and Malaria, 85% saw disruptions in HIV programs, according to a report released last month.
These service disruptions are considerable and “life threatening,” affecting some of the people at greatest risk for HIV acquisition and poor outcomes – such as people engaged in transactional sex (40%), men who have sex with men (37%), and transgender people (31%) – the 2020 Global AIDS Update, released today by UNAIDS, reports.
“In sub-Saharan Africa alone, if there is a 6-month interruption in HIV treatment services, it will account for an additional 500,000 deaths. That doubles the number of deaths in sub-Saharan Africa alone and brings us back to 2008 mortality levels,” said Shannon Hader, MD, deputy executive director of UNAIDS. “We just can’t allow that to happen.”
In addition, 73 countries are at risk of running out of HIV medications, according to a World Health Organization report, also released today.
Quantifying the impact
The impact is not the same for all patients, said Anton Pozniak, MD, consulting physician in HIV medicine at the Chelsea and Westminster Hospital in London, and international cochair of AIDS 2020.
For some, COVID-19 has not changed much. Their viral loads remain undetectable and all they need is multimonth supplies of their antiretroviral therapy (ART) medications, he told Medscape Medical News. Still, he said he worries about the well-documented effects that social isolation is having on the mental health of these patients, and the increase in substance use associated with the pandemic.
Then there is a small group of patients with HIV who had put off starting ART before the pandemic, but now want to start, he reported.
And finally, there are the people for whom the fear of COVID-19 has crippled their ability to get care.
There are people who have decided they don’t want to come to the hospital or come to the clinic because they’re scared of getting COVID-19.
“It’s really very striking,” said Dr. Pozniak. “There are people who have decided they don’t want to come to the hospital or come to the clinic because they’re scared of getting COVID-19. We’ve offered to deliver treatment, but they don’t want the stigma of parcels of drugs arriving.”
In a study presented at the conference, four of 12 care and substance-use treatment facilities in Europe and North America – including Seattle and Philadelphia – reported patients taking longer to fill ART prescriptions. And four of the 12 also reported that clients who injected drugs and were at risk for or living with HIV were having trouble adhering to prescribed therapies. In addition, at 11 of the sites, HIV testing has either nearly or completely shut down.
Structural barriers to telemedicine
And then there are structural barriers to care – poverty, lack of transportation, lack of or slow internet access, and lack of insurance – which affect 10% to 20% of the people with HIV that Jodie Dionne-Odom, MD, sees at the 1917 Ryan White HIV clinic at the University of Alabama at Birmingham.
These are the patients she said she worries about most, the ones who, even before COVID-19, were barely managing to pay their rent, car payments, and cell phone bills.
“With COVID-19 and being at home or being laid off, those things could no longer be paid. They’ve lost their phone, they’ve lost their car,” said Dionne-Odom, chief of women’s health services for the clinic. “That’s a really significant impact, because that’s exactly the group you can’t reach by telemedicine.”
In March, when the 1917 Clinic began providing the majority of services online, these people fell off the radar, said Aadia Rana, MD, associate professor of infectious diseases at the University of Alabama at Birmingham, who also works at the clinic.
This is not for lack of trying, she explained. Staff called patients weekly to check in and reschedule appointments, but there were some they just couldn’t reach.
Although the data for the second quarter have not yet been analyzed, “I would expect that our typically close to 90% viral suppression rate is going to decrease,” she said.
This decrease is likely widespread, said Rana, who is principle investigator of the Long-Acting Therapy to Improve Treatment Success in Daily Life (LATITUDE) study.
Many of the 33 sites involved in LATITUDE shut down in the early months of the pandemic, but some are now coming back online. In fact, “we are getting all these pleas from sites around the country saying, ‘Hey, once LATITUDE is open for enrollment, we have so many people who would now be eligible’,” she told Medscape Medical News.
“Why are they now eligible and they weren’t eligible before? I’m assuming it’s because they now have a detectable viral load,” which is one of the requirements for enrollment in LATITUDE, she explained.
Impact on the LGBTI community
At the onset of the COVID-19 pandemic, Erik Lamontagne, senior economist at UNAIDS, wondered how the quarantine was affecting LGBTI people.
To find out, he and his colleagues launched a survey asking just that. He is also coprinciple investigator of the LGBT Happiness Survey, a multicountry survey of LGBTI people launched last year.
The 13,562 LGBTI respondents came from 138 countries or territories. Of the 1,140 respondents living with HIV, 26% had seen their HIV care disrupted or restricted in some way during the pandemic, and 55% of those had no more than a month’s worth of HIV medications on hand.
But the pandemic hasn’t just affected people already living with HIV, Mr. Lamontagne reported. Nine of 10 respondents were living under some form of stay-at-home order, 73% were not meeting their basic needs, 37% had missed meals as a result of economic hardship, and half of those who were still working expected to lose their jobs.
Many could not afford to quarantine, Mr. Lamontagne told Medscape Medical News. And financial resources were stretched so thin that about 1% of respondents reported engaging in transactional sex for the first time. Some reported that their economic circumstances were so dire that they couldn’t require clients to wear condoms, increasing their risk for both COVID-19 and HIV.
“What they can eat in the evening is what they can earn during the day,” Mr. Lamontagne explained.
Unfortunately, it is the people already in a situation of economic vulnerability – often those from the LGBTI community – who are most affected by COVID-19, he added.
PrEP use changing
The pandemic has also affected the use of pre-exposure prophylaxis (PrEP).
South African women taking PrEP to protect themselves from HIV during pregnancy were 2.36 times more likely to miss a clinic visit to refill their prescription after COVID-19 lockdowns began than before, data presented at the conference showed. The women cited fear of acquiring COVID-19 at the medical facility, fear of police, transportation barriers, and long clinic wait times to explain the missed visits.
A study on the use of PrEP at Fenway Health, a sexual health clinic in Boston, showed a 278% increase in unfilled PrEP prescriptions after stay-at-home orders and a 72.1% drop in new PrEP prescriptions.
It’s unclear what these data, which will be presented at the conference later this week, mean, said Douglas Krakower, MD, assistant professor of medicine and population medicine at Harvard Medical School in Boston.
“We don’t know whether this represents people having trouble accessing PrEP” out of concern about getting COVID “or concerns about financial implications,” he explained.
“They may have had hardships from unemployment or other financial constraints” and have lost insurance or are still having to pay copays, he told Medscape Medical News. Or it could just be that they’re not going out or having sex, so they’ve discontinued the medication.
“Anecdotally we’ve heard that some patients are sheltering in place and not having sex and so have chosen not to use PrEP,” he added.
It’s also possible that people are rationing pills or have moved themselves to the PrEP 2-1-1 protocol, which is used only when someone is having sex, said Dr. Krakower, citing a study showing that sexual behavior is continuing as usual during quarantine for about half the gay men in the United States.
Resilience and fragility
It’s not just people living with HIV whose routines have changed during the pandemic. A survey of HIV clinicians around the world conducted by the International Association of Providers of AIDS Care showed that 88% of HIV clinicians have been pulled away from their regular work to manage COVID-19 in their communities.
But the COVID-19 pandemic shows no signs of stopping, and clinicians are now having to re-engage with their HIV patients.
“What COVID-19 has represented for us is a looking glass to see the resilience, but also the fragility, in HIV responses, not just in the global south, but also in the global north,” José Zuniga, PhD, IAPAC president and chief executive officer, said during a preconference session on controlling the HIV epidemic.
For Dr. Dionne-Odom, reopening the 1917 Clinic in Alabama meant tracking down patients who could not participate in telemedicine. Fortunately (or unfortunately, depending on how you look at it), the clinic, which serves a population with a high level of economic insecurity, has worked to get as many phone numbers as possible for each patient. So when the clinic opened back up, staff was able to call family members, friends, and trusted contacts to bring their patients back into the clinic.
“No one wanted to reopen too quickly,” said Dr. Dionne-Odom. “But having people come in allowed us to do all the other things that are the key part of HIV care: getting them connected with a social worker and making sure they have enough food, helping them with their electricity bills and their housing issues, all the wrap-around services that are so crucial for these patients.”
This article first appeared on Medscape.com.
When the COVID-19 pandemic led to a blanket shelter-in-place order in California in March, it did more than shut down in-person visits at Ward 86, the HIV clinic for publicly insured patients at San Francisco General Hospital. It also led to a decrease in viral suppression among the clinic›s clients. By the end of June, the percentage of patients with an undetectable viral load had dropped by nearly one-third.
This is exactly what Monica Gandhi, MD, associate division chief of HIV, infectious diseases, and global medicine at the University of California, San Francisco, and medical director of the clinic, was afraid of.
“We’re profoundly worried about the impact of COVID-19 on actual treatment outcomes,” said Dr. Gandhi, cochair of the virtual International AIDS Conference (AIDS) 2020.
And it’s not just the clinic’s clients at risk. Of the 106 countries served by the Global Fund to Fight HIV, Tuberculosis, and Malaria, 85% saw disruptions in HIV programs, according to a report released last month.
These service disruptions are considerable and “life threatening,” affecting some of the people at greatest risk for HIV acquisition and poor outcomes – such as people engaged in transactional sex (40%), men who have sex with men (37%), and transgender people (31%) – the 2020 Global AIDS Update, released today by UNAIDS, reports.
“In sub-Saharan Africa alone, if there is a 6-month interruption in HIV treatment services, it will account for an additional 500,000 deaths. That doubles the number of deaths in sub-Saharan Africa alone and brings us back to 2008 mortality levels,” said Shannon Hader, MD, deputy executive director of UNAIDS. “We just can’t allow that to happen.”
In addition, 73 countries are at risk of running out of HIV medications, according to a World Health Organization report, also released today.
Quantifying the impact
The impact is not the same for all patients, said Anton Pozniak, MD, consulting physician in HIV medicine at the Chelsea and Westminster Hospital in London, and international cochair of AIDS 2020.
For some, COVID-19 has not changed much. Their viral loads remain undetectable and all they need is multimonth supplies of their antiretroviral therapy (ART) medications, he told Medscape Medical News. Still, he said he worries about the well-documented effects that social isolation is having on the mental health of these patients, and the increase in substance use associated with the pandemic.
Then there is a small group of patients with HIV who had put off starting ART before the pandemic, but now want to start, he reported.
And finally, there are the people for whom the fear of COVID-19 has crippled their ability to get care.
There are people who have decided they don’t want to come to the hospital or come to the clinic because they’re scared of getting COVID-19.
“It’s really very striking,” said Dr. Pozniak. “There are people who have decided they don’t want to come to the hospital or come to the clinic because they’re scared of getting COVID-19. We’ve offered to deliver treatment, but they don’t want the stigma of parcels of drugs arriving.”
In a study presented at the conference, four of 12 care and substance-use treatment facilities in Europe and North America – including Seattle and Philadelphia – reported patients taking longer to fill ART prescriptions. And four of the 12 also reported that clients who injected drugs and were at risk for or living with HIV were having trouble adhering to prescribed therapies. In addition, at 11 of the sites, HIV testing has either nearly or completely shut down.
Structural barriers to telemedicine
And then there are structural barriers to care – poverty, lack of transportation, lack of or slow internet access, and lack of insurance – which affect 10% to 20% of the people with HIV that Jodie Dionne-Odom, MD, sees at the 1917 Ryan White HIV clinic at the University of Alabama at Birmingham.
These are the patients she said she worries about most, the ones who, even before COVID-19, were barely managing to pay their rent, car payments, and cell phone bills.
“With COVID-19 and being at home or being laid off, those things could no longer be paid. They’ve lost their phone, they’ve lost their car,” said Dionne-Odom, chief of women’s health services for the clinic. “That’s a really significant impact, because that’s exactly the group you can’t reach by telemedicine.”
In March, when the 1917 Clinic began providing the majority of services online, these people fell off the radar, said Aadia Rana, MD, associate professor of infectious diseases at the University of Alabama at Birmingham, who also works at the clinic.
This is not for lack of trying, she explained. Staff called patients weekly to check in and reschedule appointments, but there were some they just couldn’t reach.
Although the data for the second quarter have not yet been analyzed, “I would expect that our typically close to 90% viral suppression rate is going to decrease,” she said.
This decrease is likely widespread, said Rana, who is principle investigator of the Long-Acting Therapy to Improve Treatment Success in Daily Life (LATITUDE) study.
Many of the 33 sites involved in LATITUDE shut down in the early months of the pandemic, but some are now coming back online. In fact, “we are getting all these pleas from sites around the country saying, ‘Hey, once LATITUDE is open for enrollment, we have so many people who would now be eligible’,” she told Medscape Medical News.
“Why are they now eligible and they weren’t eligible before? I’m assuming it’s because they now have a detectable viral load,” which is one of the requirements for enrollment in LATITUDE, she explained.
Impact on the LGBTI community
At the onset of the COVID-19 pandemic, Erik Lamontagne, senior economist at UNAIDS, wondered how the quarantine was affecting LGBTI people.
To find out, he and his colleagues launched a survey asking just that. He is also coprinciple investigator of the LGBT Happiness Survey, a multicountry survey of LGBTI people launched last year.
The 13,562 LGBTI respondents came from 138 countries or territories. Of the 1,140 respondents living with HIV, 26% had seen their HIV care disrupted or restricted in some way during the pandemic, and 55% of those had no more than a month’s worth of HIV medications on hand.
But the pandemic hasn’t just affected people already living with HIV, Mr. Lamontagne reported. Nine of 10 respondents were living under some form of stay-at-home order, 73% were not meeting their basic needs, 37% had missed meals as a result of economic hardship, and half of those who were still working expected to lose their jobs.
Many could not afford to quarantine, Mr. Lamontagne told Medscape Medical News. And financial resources were stretched so thin that about 1% of respondents reported engaging in transactional sex for the first time. Some reported that their economic circumstances were so dire that they couldn’t require clients to wear condoms, increasing their risk for both COVID-19 and HIV.
“What they can eat in the evening is what they can earn during the day,” Mr. Lamontagne explained.
Unfortunately, it is the people already in a situation of economic vulnerability – often those from the LGBTI community – who are most affected by COVID-19, he added.
PrEP use changing
The pandemic has also affected the use of pre-exposure prophylaxis (PrEP).
South African women taking PrEP to protect themselves from HIV during pregnancy were 2.36 times more likely to miss a clinic visit to refill their prescription after COVID-19 lockdowns began than before, data presented at the conference showed. The women cited fear of acquiring COVID-19 at the medical facility, fear of police, transportation barriers, and long clinic wait times to explain the missed visits.
A study on the use of PrEP at Fenway Health, a sexual health clinic in Boston, showed a 278% increase in unfilled PrEP prescriptions after stay-at-home orders and a 72.1% drop in new PrEP prescriptions.
It’s unclear what these data, which will be presented at the conference later this week, mean, said Douglas Krakower, MD, assistant professor of medicine and population medicine at Harvard Medical School in Boston.
“We don’t know whether this represents people having trouble accessing PrEP” out of concern about getting COVID “or concerns about financial implications,” he explained.
“They may have had hardships from unemployment or other financial constraints” and have lost insurance or are still having to pay copays, he told Medscape Medical News. Or it could just be that they’re not going out or having sex, so they’ve discontinued the medication.
“Anecdotally we’ve heard that some patients are sheltering in place and not having sex and so have chosen not to use PrEP,” he added.
It’s also possible that people are rationing pills or have moved themselves to the PrEP 2-1-1 protocol, which is used only when someone is having sex, said Dr. Krakower, citing a study showing that sexual behavior is continuing as usual during quarantine for about half the gay men in the United States.
Resilience and fragility
It’s not just people living with HIV whose routines have changed during the pandemic. A survey of HIV clinicians around the world conducted by the International Association of Providers of AIDS Care showed that 88% of HIV clinicians have been pulled away from their regular work to manage COVID-19 in their communities.
But the COVID-19 pandemic shows no signs of stopping, and clinicians are now having to re-engage with their HIV patients.
“What COVID-19 has represented for us is a looking glass to see the resilience, but also the fragility, in HIV responses, not just in the global south, but also in the global north,” José Zuniga, PhD, IAPAC president and chief executive officer, said during a preconference session on controlling the HIV epidemic.
For Dr. Dionne-Odom, reopening the 1917 Clinic in Alabama meant tracking down patients who could not participate in telemedicine. Fortunately (or unfortunately, depending on how you look at it), the clinic, which serves a population with a high level of economic insecurity, has worked to get as many phone numbers as possible for each patient. So when the clinic opened back up, staff was able to call family members, friends, and trusted contacts to bring their patients back into the clinic.
“No one wanted to reopen too quickly,” said Dr. Dionne-Odom. “But having people come in allowed us to do all the other things that are the key part of HIV care: getting them connected with a social worker and making sure they have enough food, helping them with their electricity bills and their housing issues, all the wrap-around services that are so crucial for these patients.”
This article first appeared on Medscape.com.