TBD Meeting (2893-21)

Liposomal doxorubicin (Dox) plus pomalidomide (Pom) was safe and active in heavily pretreated patients with Kaposi sarcoma, according to results from a phase 1/2 trial.

“The results of our phase 1/2 study suggest pomalidomide and liposomal doxorubicin is safe with evidence of activity among patients with Kaposi sarcoma,” said investigator Ramya Ramaswami, MBBS, MPH, of the HIV & AIDS malignancy branch at the National Cancer Institute. The results were presented at the Conference on Retroviruses and Opportunistic Infections.

The researchers evaluated the safety and tolerability of Pom/Dox in two groups of patients with Kaposi sarcoma: group 1 included patients with Kaposi sarcoma alone and group 2 included patients with Kaposi sarcoma–associated herpesvirus and concurrent multicentric Castleman disease (KSHV-MCD) and KSHV inflammatory cytokine syndrome (KICS).

“Kaposi sarcoma can be challenging to treat when it co-occurs with KSHV-MCD or KICS, resulting in high mortality rates,” Dr. Ramaswami explained.

Study participants received IV liposomal Dox at 20 mg/m² on day 1 of a 28-day cycle, in addition to oral Pom once daily on days 1-21 at three escalating dose levels (2 mg, 3 mg, or 4 mg, respectively) using a standard 3 + 3 design until plateau of response, progression, dose-limiting toxicities (DLTs) or patient preference. Some eligibility criteria differed between groups 1 and 2. Participants in group 1 were required to be on antiretroviral therapy for at least 1 month and had a performance status of 2 or less, while those in group 2 had a performance status of 3 or less and could be antiretroviral therapy naive.

All participants received oral aspirin thromboprophylaxis (81 mg daily) and could have received prior Kaposi sarcoma therapy.

With respect to outcomes, Kaposi sarcoma responses were assessed using the modified AIDS Clinical Trial Group criteria and KICS and KSHV-MCD responses were evaluated using an NCI clinical benefit criteria.
 

Results

Overall, 34 cisgender men were enrolled in the study: 21 (62%) in group 1 and 13 (38%) in group 2. All participants had severe (T1) Kaposi sarcoma; 32 (94%) participants were HIV-infected and 22 (65%) had prior chemotherapy for Kaposi sarcoma.

While the HIV viral load was largely controlled in both groups, the CD4 count differed, with median CD4 counts of 286 and 92 cells/mcL in groups 1 and 2, respectively.

With respect to safety, no DLTs were observed in group 1. As a result, 12 participants were treated at the maximum tolerated dose (MTD) of 4 mg of Pom. However, two DLTs (grade 3 rash and pharyngeal edema) were observed in group 2 at the 3 mg dose level.

A median of six cycles were administered for all participants and the most common grade 3/4 toxicity was neutropenia; nine patients with grade 3 neutropenia required dose reduction and three patients had febrile neutropenia requiring hospitalization. Other Pom-related adverse events were rash, constipation, and fatigue.

Among evaluable participants receiving two or more cycles, 17 (81%) patients in group 1 had a response (95% confidence interval, 58-95%; 16 partial response and 1 complete response) and 5 (50%) patients in group 2 had a response (95% CI, 19-81%; 4 PR and 1 CR).

“Our waterfall plots indicated that the vast majority of patients in group 1 had a positive change in nodular lesions at baseline,” Dr. Ramaswami said. “Participants in group 2 showed some decrease in nodular lesions, but this was usually temporary.”

Among seven participants with KICS responses, four participants (57%) experienced a CR or PR in symptoms and lab abnormalities associated with KICS; three of six participants (50%) with KSHV-MCD responses experienced a PR as per response criteria.

“While activity was noted, the combination was less well tolerated in patients with Kaposi sarcoma and concurrent KSHV-MCD or KICS,” Dr. Ramaswami said.

During a live discussion, Ronald T. Mitsuyasu, MD, of the University of California, Los Angeles, asked Dr. Ramaswami about the use of liposomal doxorubicin alone in patients with Kaposi sarcoma and concurrent KSHV-MCD or KICS.

While there is currently no data on the use of doxorubicin alone in this population, Dr. Ramaswami noted that she was more confident administering Pom/Dox combination therapy for these patients.

Dr. Ramaswami disclosed financial relationships with the National Cancer Institute, Celgene/Bristol-Myers Squibb, EMD Serono, Merck, CTI Biopharma, and Janssen. The study was funded by a cooperative research and drug development agreement between the National Cancer Institute and Celgene/BMS, EMD Serono, Merck, CTI Biopharma, and Janssen.

Liposomal doxorubicin (Dox) plus pomalidomide (Pom) was safe and active in heavily pretreated patients with Kaposi sarcoma, according to results from a phase 1/2 trial.

“The results of our phase 1/2 study suggest pomalidomide and liposomal doxorubicin is safe with evidence of activity among patients with Kaposi sarcoma,” said investigator Ramya Ramaswami, MBBS, MPH, of the HIV & AIDS malignancy branch at the National Cancer Institute. The results were presented at the Conference on Retroviruses and Opportunistic Infections.

The researchers evaluated the safety and tolerability of Pom/Dox in two groups of patients with Kaposi sarcoma: group 1 included patients with Kaposi sarcoma alone and group 2 included patients with Kaposi sarcoma–associated herpesvirus and concurrent multicentric Castleman disease (KSHV-MCD) and KSHV inflammatory cytokine syndrome (KICS).

“Kaposi sarcoma can be challenging to treat when it co-occurs with KSHV-MCD or KICS, resulting in high mortality rates,” Dr. Ramaswami explained.

Study participants received IV liposomal Dox at 20 mg/m² on day 1 of a 28-day cycle, in addition to oral Pom once daily on days 1-21 at three escalating dose levels (2 mg, 3 mg, or 4 mg, respectively) using a standard 3 + 3 design until plateau of response, progression, dose-limiting toxicities (DLTs) or patient preference. Some eligibility criteria differed between groups 1 and 2. Participants in group 1 were required to be on antiretroviral therapy for at least 1 month and had a performance status of 2 or less, while those in group 2 had a performance status of 3 or less and could be antiretroviral therapy naive.

All participants received oral aspirin thromboprophylaxis (81 mg daily) and could have received prior Kaposi sarcoma therapy.

With respect to outcomes, Kaposi sarcoma responses were assessed using the modified AIDS Clinical Trial Group criteria and KICS and KSHV-MCD responses were evaluated using an NCI clinical benefit criteria.
 

Results

Overall, 34 cisgender men were enrolled in the study: 21 (62%) in group 1 and 13 (38%) in group 2. All participants had severe (T1) Kaposi sarcoma; 32 (94%) participants were HIV-infected and 22 (65%) had prior chemotherapy for Kaposi sarcoma.

While the HIV viral load was largely controlled in both groups, the CD4 count differed, with median CD4 counts of 286 and 92 cells/mcL in groups 1 and 2, respectively.

With respect to safety, no DLTs were observed in group 1. As a result, 12 participants were treated at the maximum tolerated dose (MTD) of 4 mg of Pom. However, two DLTs (grade 3 rash and pharyngeal edema) were observed in group 2 at the 3 mg dose level.

A median of six cycles were administered for all participants and the most common grade 3/4 toxicity was neutropenia; nine patients with grade 3 neutropenia required dose reduction and three patients had febrile neutropenia requiring hospitalization. Other Pom-related adverse events were rash, constipation, and fatigue.

Among evaluable participants receiving two or more cycles, 17 (81%) patients in group 1 had a response (95% confidence interval, 58-95%; 16 partial response and 1 complete response) and 5 (50%) patients in group 2 had a response (95% CI, 19-81%; 4 PR and 1 CR).

“Our waterfall plots indicated that the vast majority of patients in group 1 had a positive change in nodular lesions at baseline,” Dr. Ramaswami said. “Participants in group 2 showed some decrease in nodular lesions, but this was usually temporary.”

Among seven participants with KICS responses, four participants (57%) experienced a CR or PR in symptoms and lab abnormalities associated with KICS; three of six participants (50%) with KSHV-MCD responses experienced a PR as per response criteria.

“While activity was noted, the combination was less well tolerated in patients with Kaposi sarcoma and concurrent KSHV-MCD or KICS,” Dr. Ramaswami said.

During a live discussion, Ronald T. Mitsuyasu, MD, of the University of California, Los Angeles, asked Dr. Ramaswami about the use of liposomal doxorubicin alone in patients with Kaposi sarcoma and concurrent KSHV-MCD or KICS.

While there is currently no data on the use of doxorubicin alone in this population, Dr. Ramaswami noted that she was more confident administering Pom/Dox combination therapy for these patients.

Dr. Ramaswami disclosed financial relationships with the National Cancer Institute, Celgene/Bristol-Myers Squibb, EMD Serono, Merck, CTI Biopharma, and Janssen. The study was funded by a cooperative research and drug development agreement between the National Cancer Institute and Celgene/BMS, EMD Serono, Merck, CTI Biopharma, and Janssen.

Liposomal doxorubicin (Dox) plus pomalidomide (Pom) was safe and active in heavily pretreated patients with Kaposi sarcoma, according to results from a phase 1/2 trial.

“The results of our phase 1/2 study suggest pomalidomide and liposomal doxorubicin is safe with evidence of activity among patients with Kaposi sarcoma,” said investigator Ramya Ramaswami, MBBS, MPH, of the HIV & AIDS malignancy branch at the National Cancer Institute. The results were presented at the Conference on Retroviruses and Opportunistic Infections.

The researchers evaluated the safety and tolerability of Pom/Dox in two groups of patients with Kaposi sarcoma: group 1 included patients with Kaposi sarcoma alone and group 2 included patients with Kaposi sarcoma–associated herpesvirus and concurrent multicentric Castleman disease (KSHV-MCD) and KSHV inflammatory cytokine syndrome (KICS).

“Kaposi sarcoma can be challenging to treat when it co-occurs with KSHV-MCD or KICS, resulting in high mortality rates,” Dr. Ramaswami explained.

Study participants received IV liposomal Dox at 20 mg/m² on day 1 of a 28-day cycle, in addition to oral Pom once daily on days 1-21 at three escalating dose levels (2 mg, 3 mg, or 4 mg, respectively) using a standard 3 + 3 design until plateau of response, progression, dose-limiting toxicities (DLTs) or patient preference. Some eligibility criteria differed between groups 1 and 2. Participants in group 1 were required to be on antiretroviral therapy for at least 1 month and had a performance status of 2 or less, while those in group 2 had a performance status of 3 or less and could be antiretroviral therapy naive.

All participants received oral aspirin thromboprophylaxis (81 mg daily) and could have received prior Kaposi sarcoma therapy.

With respect to outcomes, Kaposi sarcoma responses were assessed using the modified AIDS Clinical Trial Group criteria and KICS and KSHV-MCD responses were evaluated using an NCI clinical benefit criteria.
 

Results

Overall, 34 cisgender men were enrolled in the study: 21 (62%) in group 1 and 13 (38%) in group 2. All participants had severe (T1) Kaposi sarcoma; 32 (94%) participants were HIV-infected and 22 (65%) had prior chemotherapy for Kaposi sarcoma.

While the HIV viral load was largely controlled in both groups, the CD4 count differed, with median CD4 counts of 286 and 92 cells/mcL in groups 1 and 2, respectively.

With respect to safety, no DLTs were observed in group 1. As a result, 12 participants were treated at the maximum tolerated dose (MTD) of 4 mg of Pom. However, two DLTs (grade 3 rash and pharyngeal edema) were observed in group 2 at the 3 mg dose level.

A median of six cycles were administered for all participants and the most common grade 3/4 toxicity was neutropenia; nine patients with grade 3 neutropenia required dose reduction and three patients had febrile neutropenia requiring hospitalization. Other Pom-related adverse events were rash, constipation, and fatigue.

Among evaluable participants receiving two or more cycles, 17 (81%) patients in group 1 had a response (95% confidence interval, 58-95%; 16 partial response and 1 complete response) and 5 (50%) patients in group 2 had a response (95% CI, 19-81%; 4 PR and 1 CR).

“Our waterfall plots indicated that the vast majority of patients in group 1 had a positive change in nodular lesions at baseline,” Dr. Ramaswami said. “Participants in group 2 showed some decrease in nodular lesions, but this was usually temporary.”

Among seven participants with KICS responses, four participants (57%) experienced a CR or PR in symptoms and lab abnormalities associated with KICS; three of six participants (50%) with KSHV-MCD responses experienced a PR as per response criteria.

“While activity was noted, the combination was less well tolerated in patients with Kaposi sarcoma and concurrent KSHV-MCD or KICS,” Dr. Ramaswami said.

During a live discussion, Ronald T. Mitsuyasu, MD, of the University of California, Los Angeles, asked Dr. Ramaswami about the use of liposomal doxorubicin alone in patients with Kaposi sarcoma and concurrent KSHV-MCD or KICS.

While there is currently no data on the use of doxorubicin alone in this population, Dr. Ramaswami noted that she was more confident administering Pom/Dox combination therapy for these patients.

Dr. Ramaswami disclosed financial relationships with the National Cancer Institute, Celgene/Bristol-Myers Squibb, EMD Serono, Merck, CTI Biopharma, and Janssen. The study was funded by a cooperative research and drug development agreement between the National Cancer Institute and Celgene/BMS, EMD Serono, Merck, CTI Biopharma, and Janssen.

Elevated vaginal pH at the time of cervical intraepithelial neoplasia 2 diagnosis may be a useful marker of CIN 2 persistence/progression, as well as the rate of persistence/progression in HIV-positive women, new research suggests.

“We analyzed data from the Women’s Interagency HIV Study [WIHS], an observational, longitudinal cohort of women with and without HIV to determine factors that may influence CIN 2 natural history,” said Kate Michel, PhD, MPH, of Georgetown University, Washington. She presented the results at the Conference on Retroviruses and Opportunistic Infections.

As previous data have shown a high incidence of CIN 2 progression among women with HIV, the researchers evaluated the role of human papillomavirus (HPV) type, local immune response, and markers of the cervicovaginal microbiome on the risk of CIN 2 persistence/progression.

Within the cohort, follow-up visits occur every 6 months, and clinical data is collected via questionnaires, physical and gynecologic exams, and biological samples. As no specific treatment is offered in the WIHS, treatment for cervical abnormalities is abstracted from medical records.

In the present study, Dr. Michel and colleagues selected up to four banked cervicovaginal lavage (CVL) samples per woman, with the first sample selected 6-12 months prior to CIN 2 diagnosis, the second at CIN 2 diagnosis, the third between CIN 2 diagnosis and outcome, and the fourth at the outcome visit.

The investigators performed HPV typing and muiltiplex immune mediator testing on each CVL sample. Lab results from WIHS core testing were also extracted, including plasma CD4+ T-cell count and HIV viral load, as well as vaginal pH and Nugent’s score.

Study outcomes included persistence/progression and regression, defined as a subsequent CIN 2 or CIN 3 diagnosis and subsequent CIN 1 or normal diagnosis, respectively. Logistic regression models were used to determine CIN 2 regression versus persistence/progression.
 

Results

A total of 337 samples were obtained and 94 women were included in the analysis. Key demographic and behavioral factor were similar at CIN 2 diagnosis.

The majority of participants were African American (53.2%) and on antiretroviral therapy (66.0%). The most prevalent high-risk types were HPV-58 (18.4%) and HPV-16 (17.5%).

After a median 12.5 years of follow-up, 33 participants (35.1%) with incident CIN 2 had a subsequent CIN 2/CIN 3 diagnosis and those who regressed had a higher CD4 T-cell count at CIN 2 diagnosis (P = .02).

Each subsequent high-risk HPV type identified at the pre–CIN 2 visit was associated with higher odds of CIN2 persistence/progression (odds ratio, 2.27; 95% confidence interval, 1.15-4.50).

Bacterial vaginosis (adjusted OR, 5.08; 95% CI, 1.30-19.94) and vaginal pH (aOR, 2.27; 95% CI, 1.15-4.50) at the CIN 2 diagnosis visit were each associated with increased odds of CIN 2 persistence/progression.

Vaginal pH greater than 4.5 at CIN 2 diagnosis was also associated with unadjusted time to CIN 2 persistence/progression (log rank P = .002) and an increased rate of CIN 2 persistence/progression (adjusted hazard ratio, 3.37; 95% CI, 1.26-8.99).

Furthermore, among participants who did not receive CIN 2 treatment, vaginal pH remained associated with greater odds of CIN 2 persistence/progression (OR, 2.46; 95% CI, 1.19-5.13). Cervicovaginal immune mediator levels were not associated with CIN 2 persistence/progression.

“The most striking finding from this work was that vaginal pH was associated with higher odds of, quicker time to, and increased hazard of CIN 2 persistence/progression,” Dr. Michel said. “We postulate this effect is mediated by the cervical microbiome, but more work is needed to establish the exact mechanism.”

“It would be interesting to test whether this association might be explained by different vaginal cleaning techniques, such as douching,” said moderator Ronald T. Mitsuyasu, MD, of the University of California, Los Angeles.

“We’re currently working on an analysis of cervicovaginal bacterial species to explore the microbiome in more detail,” Dr. Michel concluded.

Dr. Michel disclosed no conflicts of interest. The study was supported by multiple sources, including the National Institute of Allergy and Infectious Diseases, the National Cancer Institute, and the Georgetown-Howard Universities Center for Clinical and Translational Science.

Elevated vaginal pH at the time of cervical intraepithelial neoplasia 2 diagnosis may be a useful marker of CIN 2 persistence/progression, as well as the rate of persistence/progression in HIV-positive women, new research suggests.

“We analyzed data from the Women’s Interagency HIV Study [WIHS], an observational, longitudinal cohort of women with and without HIV to determine factors that may influence CIN 2 natural history,” said Kate Michel, PhD, MPH, of Georgetown University, Washington. She presented the results at the Conference on Retroviruses and Opportunistic Infections.

As previous data have shown a high incidence of CIN 2 progression among women with HIV, the researchers evaluated the role of human papillomavirus (HPV) type, local immune response, and markers of the cervicovaginal microbiome on the risk of CIN 2 persistence/progression.

Within the cohort, follow-up visits occur every 6 months, and clinical data is collected via questionnaires, physical and gynecologic exams, and biological samples. As no specific treatment is offered in the WIHS, treatment for cervical abnormalities is abstracted from medical records.

In the present study, Dr. Michel and colleagues selected up to four banked cervicovaginal lavage (CVL) samples per woman, with the first sample selected 6-12 months prior to CIN 2 diagnosis, the second at CIN 2 diagnosis, the third between CIN 2 diagnosis and outcome, and the fourth at the outcome visit.

The investigators performed HPV typing and muiltiplex immune mediator testing on each CVL sample. Lab results from WIHS core testing were also extracted, including plasma CD4+ T-cell count and HIV viral load, as well as vaginal pH and Nugent’s score.

Study outcomes included persistence/progression and regression, defined as a subsequent CIN 2 or CIN 3 diagnosis and subsequent CIN 1 or normal diagnosis, respectively. Logistic regression models were used to determine CIN 2 regression versus persistence/progression.
 

Results

A total of 337 samples were obtained and 94 women were included in the analysis. Key demographic and behavioral factor were similar at CIN 2 diagnosis.

The majority of participants were African American (53.2%) and on antiretroviral therapy (66.0%). The most prevalent high-risk types were HPV-58 (18.4%) and HPV-16 (17.5%).

After a median 12.5 years of follow-up, 33 participants (35.1%) with incident CIN 2 had a subsequent CIN 2/CIN 3 diagnosis and those who regressed had a higher CD4 T-cell count at CIN 2 diagnosis (P = .02).

Each subsequent high-risk HPV type identified at the pre–CIN 2 visit was associated with higher odds of CIN2 persistence/progression (odds ratio, 2.27; 95% confidence interval, 1.15-4.50).

Bacterial vaginosis (adjusted OR, 5.08; 95% CI, 1.30-19.94) and vaginal pH (aOR, 2.27; 95% CI, 1.15-4.50) at the CIN 2 diagnosis visit were each associated with increased odds of CIN 2 persistence/progression.

Vaginal pH greater than 4.5 at CIN 2 diagnosis was also associated with unadjusted time to CIN 2 persistence/progression (log rank P = .002) and an increased rate of CIN 2 persistence/progression (adjusted hazard ratio, 3.37; 95% CI, 1.26-8.99).

Furthermore, among participants who did not receive CIN 2 treatment, vaginal pH remained associated with greater odds of CIN 2 persistence/progression (OR, 2.46; 95% CI, 1.19-5.13). Cervicovaginal immune mediator levels were not associated with CIN 2 persistence/progression.

“The most striking finding from this work was that vaginal pH was associated with higher odds of, quicker time to, and increased hazard of CIN 2 persistence/progression,” Dr. Michel said. “We postulate this effect is mediated by the cervical microbiome, but more work is needed to establish the exact mechanism.”

“It would be interesting to test whether this association might be explained by different vaginal cleaning techniques, such as douching,” said moderator Ronald T. Mitsuyasu, MD, of the University of California, Los Angeles.

“We’re currently working on an analysis of cervicovaginal bacterial species to explore the microbiome in more detail,” Dr. Michel concluded.

Dr. Michel disclosed no conflicts of interest. The study was supported by multiple sources, including the National Institute of Allergy and Infectious Diseases, the National Cancer Institute, and the Georgetown-Howard Universities Center for Clinical and Translational Science.

Elevated vaginal pH at the time of cervical intraepithelial neoplasia 2 diagnosis may be a useful marker of CIN 2 persistence/progression, as well as the rate of persistence/progression in HIV-positive women, new research suggests.

“We analyzed data from the Women’s Interagency HIV Study [WIHS], an observational, longitudinal cohort of women with and without HIV to determine factors that may influence CIN 2 natural history,” said Kate Michel, PhD, MPH, of Georgetown University, Washington. She presented the results at the Conference on Retroviruses and Opportunistic Infections.

As previous data have shown a high incidence of CIN 2 progression among women with HIV, the researchers evaluated the role of human papillomavirus (HPV) type, local immune response, and markers of the cervicovaginal microbiome on the risk of CIN 2 persistence/progression.

Within the cohort, follow-up visits occur every 6 months, and clinical data is collected via questionnaires, physical and gynecologic exams, and biological samples. As no specific treatment is offered in the WIHS, treatment for cervical abnormalities is abstracted from medical records.

In the present study, Dr. Michel and colleagues selected up to four banked cervicovaginal lavage (CVL) samples per woman, with the first sample selected 6-12 months prior to CIN 2 diagnosis, the second at CIN 2 diagnosis, the third between CIN 2 diagnosis and outcome, and the fourth at the outcome visit.

The investigators performed HPV typing and muiltiplex immune mediator testing on each CVL sample. Lab results from WIHS core testing were also extracted, including plasma CD4+ T-cell count and HIV viral load, as well as vaginal pH and Nugent’s score.

Study outcomes included persistence/progression and regression, defined as a subsequent CIN 2 or CIN 3 diagnosis and subsequent CIN 1 or normal diagnosis, respectively. Logistic regression models were used to determine CIN 2 regression versus persistence/progression.
 

Results

A total of 337 samples were obtained and 94 women were included in the analysis. Key demographic and behavioral factor were similar at CIN 2 diagnosis.

The majority of participants were African American (53.2%) and on antiretroviral therapy (66.0%). The most prevalent high-risk types were HPV-58 (18.4%) and HPV-16 (17.5%).

After a median 12.5 years of follow-up, 33 participants (35.1%) with incident CIN 2 had a subsequent CIN 2/CIN 3 diagnosis and those who regressed had a higher CD4 T-cell count at CIN 2 diagnosis (P = .02).

Each subsequent high-risk HPV type identified at the pre–CIN 2 visit was associated with higher odds of CIN2 persistence/progression (odds ratio, 2.27; 95% confidence interval, 1.15-4.50).

Bacterial vaginosis (adjusted OR, 5.08; 95% CI, 1.30-19.94) and vaginal pH (aOR, 2.27; 95% CI, 1.15-4.50) at the CIN 2 diagnosis visit were each associated with increased odds of CIN 2 persistence/progression.

Vaginal pH greater than 4.5 at CIN 2 diagnosis was also associated with unadjusted time to CIN 2 persistence/progression (log rank P = .002) and an increased rate of CIN 2 persistence/progression (adjusted hazard ratio, 3.37; 95% CI, 1.26-8.99).

Furthermore, among participants who did not receive CIN 2 treatment, vaginal pH remained associated with greater odds of CIN 2 persistence/progression (OR, 2.46; 95% CI, 1.19-5.13). Cervicovaginal immune mediator levels were not associated with CIN 2 persistence/progression.

“The most striking finding from this work was that vaginal pH was associated with higher odds of, quicker time to, and increased hazard of CIN 2 persistence/progression,” Dr. Michel said. “We postulate this effect is mediated by the cervical microbiome, but more work is needed to establish the exact mechanism.”

“It would be interesting to test whether this association might be explained by different vaginal cleaning techniques, such as douching,” said moderator Ronald T. Mitsuyasu, MD, of the University of California, Los Angeles.

“We’re currently working on an analysis of cervicovaginal bacterial species to explore the microbiome in more detail,” Dr. Michel concluded.

Dr. Michel disclosed no conflicts of interest. The study was supported by multiple sources, including the National Institute of Allergy and Infectious Diseases, the National Cancer Institute, and the Georgetown-Howard Universities Center for Clinical and Translational Science.

A novel minimal monitoring (MINMON) approach to hepatitis C virus (HCV) treatment was safe and achieved sustained virology response (SVR) compared to current clinical standards in treatment-naive patients without evidence of decompensated cirrhosis, according to a recent study.

©Jezperklauzen/ThinkStock

“This model may allow for HCV elimination, while minimizing resource use and face-to-face contact,” said investigator Sunil S. Solomon, MBBS, PhD, of Johns Hopkins University in Baltimore. “The COVID-19 pandemic has highlighted the urgent need for simple and safe models of HCV [care] delivery.”

Dr. Solomon described the new approach to HCV treatment during a presentation at this year’s Conference on Retroviruses and Opportunistic Infections virtual meeting.
 

Study design

ACTG A5360 was an international, single-arm, open-label, phase 4 trial that enrolled 400 patients across 38 treatment sites.

The researchers evaluated the efficacy and safety of the MINMON approach in treatment-naive individuals who had no evidence of decompensated cirrhosis. Study participants received a fixed-dose, single-tablet regimen of sofosbuvir 400 mg/velpatasvir 100 mg once daily for 12 weeks.

The MINMON approach comprised four key elements: no pretreatment genotyping, all tablets dispensed at study entry, no scheduled on-treatment clinic visits/labs, and two remote contacts at weeks 4 (adherence evaluation) and 22 (scheduled SVR visit). Unplanned visits for patients concerns were permitted.

Key eligibility criteria included active HCV infection (HCV RNA > 1,000 IU/mL) and no prior HCV treatment history. Persons with HIV coinfection (50% or less of sample) and compensated cirrhosis (20% or less of sample) were also eligible. Persons with chronic hepatitis B virus (HBV) infection and decompensated cirrhosis were excluded.

The primary efficacy endpoint was SVR, defined as HCV RNA less than the lower limit of quantification in the first sample at least 22 weeks post treatment initiation. The primary safety endpoint was any serious adverse events (AEs) occurring between treatment initiation and week 28.
 

Results

Among 400 patients enrolled, 399 (99.8%) were included in the primary efficacy analysis and 397 (99.3%) were included in the safety analysis. The median age of participants was 47 years, and 35% were female sex at birth. At baseline, 166 (42%) patients had HIV coinfection and 34 (9%) had compensated cirrhosis.

After analysis, the researchers found that remote contact was successful at weeks 4 and 22 for 394 (98.7%) and 335 (84.0%) participants, respectively.

In total, 15 (3.8%) participants recorded 21 unplanned visits, 3 (14.3%) of which were due to AEs, none of which were treatment related. Three participants reported losing study medications and one participant prematurely discontinued therapy due to an AE.

HCV RNA data at SVR were available for 396 participants. Overall, 379 patients (95.0%) achieved SVR (95% confidence interval [CI], 92.4%-96.7%).

“The study was not powered for SVR by subgroups, which explains why we observed wide confidence intervals in our forest plot,” Dr. Solomon said.

With respect to safety, serious AEs were reported in 14 (3.5%) participants through week 24 visit, none of which were treatment related or resulted in death.

Dr. Solomon acknowledged that a key limitation of the study was the single-arm design. As a result, there was no direct comparison to standard monitoring practices. In addition, these results may not be generalizable to all nonresearch treatment sites.

“The COVID-19 pandemic has required us to pivot clinical programs to minimize in-person contact, and promote more remote approaches, which is really the essence of the MINMON approach,” Dr. Solomon explained.

“There are really wonderful results in the population that was studied, but may reflect a more adherent patient population,” said moderator Robert T. Schooley, MD, of the University of California, San Diego.

During a discussion, Dr. Solomon noted that the MINMON approach may be further explored in patients who are actively injecting drugs, as these patients were not well represented in the present study.

Dr. Solomon disclosed financial relationships with Gilead Sciences and Abbott Diagnostics. The study was funded by the National Institutes of Health and Gilead Sciences.

A novel minimal monitoring (MINMON) approach to hepatitis C virus (HCV) treatment was safe and achieved sustained virology response (SVR) compared to current clinical standards in treatment-naive patients without evidence of decompensated cirrhosis, according to a recent study.

©Jezperklauzen/ThinkStock

“This model may allow for HCV elimination, while minimizing resource use and face-to-face contact,” said investigator Sunil S. Solomon, MBBS, PhD, of Johns Hopkins University in Baltimore. “The COVID-19 pandemic has highlighted the urgent need for simple and safe models of HCV [care] delivery.”

Dr. Solomon described the new approach to HCV treatment during a presentation at this year’s Conference on Retroviruses and Opportunistic Infections virtual meeting.
 

Study design

ACTG A5360 was an international, single-arm, open-label, phase 4 trial that enrolled 400 patients across 38 treatment sites.

The researchers evaluated the efficacy and safety of the MINMON approach in treatment-naive individuals who had no evidence of decompensated cirrhosis. Study participants received a fixed-dose, single-tablet regimen of sofosbuvir 400 mg/velpatasvir 100 mg once daily for 12 weeks.

The MINMON approach comprised four key elements: no pretreatment genotyping, all tablets dispensed at study entry, no scheduled on-treatment clinic visits/labs, and two remote contacts at weeks 4 (adherence evaluation) and 22 (scheduled SVR visit). Unplanned visits for patients concerns were permitted.

Key eligibility criteria included active HCV infection (HCV RNA > 1,000 IU/mL) and no prior HCV treatment history. Persons with HIV coinfection (50% or less of sample) and compensated cirrhosis (20% or less of sample) were also eligible. Persons with chronic hepatitis B virus (HBV) infection and decompensated cirrhosis were excluded.

The primary efficacy endpoint was SVR, defined as HCV RNA less than the lower limit of quantification in the first sample at least 22 weeks post treatment initiation. The primary safety endpoint was any serious adverse events (AEs) occurring between treatment initiation and week 28.
 

Results

Among 400 patients enrolled, 399 (99.8%) were included in the primary efficacy analysis and 397 (99.3%) were included in the safety analysis. The median age of participants was 47 years, and 35% were female sex at birth. At baseline, 166 (42%) patients had HIV coinfection and 34 (9%) had compensated cirrhosis.

After analysis, the researchers found that remote contact was successful at weeks 4 and 22 for 394 (98.7%) and 335 (84.0%) participants, respectively.

In total, 15 (3.8%) participants recorded 21 unplanned visits, 3 (14.3%) of which were due to AEs, none of which were treatment related. Three participants reported losing study medications and one participant prematurely discontinued therapy due to an AE.

HCV RNA data at SVR were available for 396 participants. Overall, 379 patients (95.0%) achieved SVR (95% confidence interval [CI], 92.4%-96.7%).

“The study was not powered for SVR by subgroups, which explains why we observed wide confidence intervals in our forest plot,” Dr. Solomon said.

With respect to safety, serious AEs were reported in 14 (3.5%) participants through week 24 visit, none of which were treatment related or resulted in death.

Dr. Solomon acknowledged that a key limitation of the study was the single-arm design. As a result, there was no direct comparison to standard monitoring practices. In addition, these results may not be generalizable to all nonresearch treatment sites.

“The COVID-19 pandemic has required us to pivot clinical programs to minimize in-person contact, and promote more remote approaches, which is really the essence of the MINMON approach,” Dr. Solomon explained.

“There are really wonderful results in the population that was studied, but may reflect a more adherent patient population,” said moderator Robert T. Schooley, MD, of the University of California, San Diego.

During a discussion, Dr. Solomon noted that the MINMON approach may be further explored in patients who are actively injecting drugs, as these patients were not well represented in the present study.

Dr. Solomon disclosed financial relationships with Gilead Sciences and Abbott Diagnostics. The study was funded by the National Institutes of Health and Gilead Sciences.

A novel minimal monitoring (MINMON) approach to hepatitis C virus (HCV) treatment was safe and achieved sustained virology response (SVR) compared to current clinical standards in treatment-naive patients without evidence of decompensated cirrhosis, according to a recent study.

©Jezperklauzen/ThinkStock

“This model may allow for HCV elimination, while minimizing resource use and face-to-face contact,” said investigator Sunil S. Solomon, MBBS, PhD, of Johns Hopkins University in Baltimore. “The COVID-19 pandemic has highlighted the urgent need for simple and safe models of HCV [care] delivery.”

Dr. Solomon described the new approach to HCV treatment during a presentation at this year’s Conference on Retroviruses and Opportunistic Infections virtual meeting.
 

Study design

ACTG A5360 was an international, single-arm, open-label, phase 4 trial that enrolled 400 patients across 38 treatment sites.

The researchers evaluated the efficacy and safety of the MINMON approach in treatment-naive individuals who had no evidence of decompensated cirrhosis. Study participants received a fixed-dose, single-tablet regimen of sofosbuvir 400 mg/velpatasvir 100 mg once daily for 12 weeks.

The MINMON approach comprised four key elements: no pretreatment genotyping, all tablets dispensed at study entry, no scheduled on-treatment clinic visits/labs, and two remote contacts at weeks 4 (adherence evaluation) and 22 (scheduled SVR visit). Unplanned visits for patients concerns were permitted.

Key eligibility criteria included active HCV infection (HCV RNA > 1,000 IU/mL) and no prior HCV treatment history. Persons with HIV coinfection (50% or less of sample) and compensated cirrhosis (20% or less of sample) were also eligible. Persons with chronic hepatitis B virus (HBV) infection and decompensated cirrhosis were excluded.

The primary efficacy endpoint was SVR, defined as HCV RNA less than the lower limit of quantification in the first sample at least 22 weeks post treatment initiation. The primary safety endpoint was any serious adverse events (AEs) occurring between treatment initiation and week 28.
 

Results

Among 400 patients enrolled, 399 (99.8%) were included in the primary efficacy analysis and 397 (99.3%) were included in the safety analysis. The median age of participants was 47 years, and 35% were female sex at birth. At baseline, 166 (42%) patients had HIV coinfection and 34 (9%) had compensated cirrhosis.

After analysis, the researchers found that remote contact was successful at weeks 4 and 22 for 394 (98.7%) and 335 (84.0%) participants, respectively.

In total, 15 (3.8%) participants recorded 21 unplanned visits, 3 (14.3%) of which were due to AEs, none of which were treatment related. Three participants reported losing study medications and one participant prematurely discontinued therapy due to an AE.

HCV RNA data at SVR were available for 396 participants. Overall, 379 patients (95.0%) achieved SVR (95% confidence interval [CI], 92.4%-96.7%).

“The study was not powered for SVR by subgroups, which explains why we observed wide confidence intervals in our forest plot,” Dr. Solomon said.

With respect to safety, serious AEs were reported in 14 (3.5%) participants through week 24 visit, none of which were treatment related or resulted in death.

Dr. Solomon acknowledged that a key limitation of the study was the single-arm design. As a result, there was no direct comparison to standard monitoring practices. In addition, these results may not be generalizable to all nonresearch treatment sites.

“The COVID-19 pandemic has required us to pivot clinical programs to minimize in-person contact, and promote more remote approaches, which is really the essence of the MINMON approach,” Dr. Solomon explained.

“There are really wonderful results in the population that was studied, but may reflect a more adherent patient population,” said moderator Robert T. Schooley, MD, of the University of California, San Diego.

During a discussion, Dr. Solomon noted that the MINMON approach may be further explored in patients who are actively injecting drugs, as these patients were not well represented in the present study.

Dr. Solomon disclosed financial relationships with Gilead Sciences and Abbott Diagnostics. The study was funded by the National Institutes of Health and Gilead Sciences.

Any level of hepatitis B virus (HBV) viremia was associated with increased hepatocellular carcinoma (HCC) risk in adults with HIV/HBV coinfection, according to new research presented at the Conference on Retroviruses and Opportunistic Infections (Abstract 136).

sarathsasidharan/Thinkstock

“Chronic HBV coinfection is common among people with HIV, but the determinants of HBV-associated HCC are not well characterized,” said presenter H. Nina Kim MD, MSc, of the University of Washington, Seattle. “We sought to identify factors that contribute to HCC development in persons with HIV/HBV coinfection to guide early detection and prevention measures.”

The researchers conducted a longitudinal cohort study within the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD), a collaboration of single-site and multisite cohorts throughout the United States and Canada; 22 cohorts from NA-ACCORD were included in the analysis.

Potential HIV and HBV risk factors were examined, including viremia and CD4 percentage, as well as HBV DNA levels. Traditional risk factors for liver disease progression, including age, sex, and heavy alcohol use, were also assessed.

Eligible patients were 18 years of age or older who were followed for at least 6 months, had evidence of chronic HBV, and had HIV RNA or CD4+ cell measurement during this period. Persons with prevalent HCC at baseline were excluded.

The primary outcome was first occurrence of HCC, which was adjudicated by medical chart review and/or cancer registry. Multivariable Cox regression was used to determine adjusted hazard ratios of risk factors.
 

Results

Among 9,383 HIV/HBV-coinfected individuals identified, 8,354 (89%) were included in the analysis. The median age of participants was 43 years and 93.1% were male. Heavy alcohol use (35.3%) and chronic hepatitis C virus (HCV) coinfection (21.6%) were common among participants.

Among 8,354 eligible participants, 115 developed HCC over a median 6.9 years of follow-up (incidence rate, 1.8 events per 1,000 person-years; 95% confidence interval [CI], 1.5-2.1).

Independent risk factors for HCC were chronic HCV coinfection (adjusted hazard ratio [aHR], 1.60 [95% confidence interval, 1.07-2.39]), age 40 years and older (aHR, 2.14 [1.36-3.37]), and heavy alcohol use (aHR, 1.51 [1.03-2.21]); however, time-updated CD4+ percentage less than 14% (aHR, 1.03 [0.56-1.90]) and time-updated HIV RNA level over 500 copies/mL (aHR, 0.88 [0.55-1.41]) were not associated with HCC risk.

In a second model, among 3,054 patients who had HBV DNA measured, the risk of HCC was higher with HBV DNA levels greater than 200 IU/mL (aHR, 2.70 [1.23-5.93]), and the risk was particularly elevated at levels greater than 200,000 IU/mL (aHR, 4.34 [1.72-10.94]).

The researchers also found that the risk of HCC was significantly lower in patients with HBV DNA suppression less than 200 IU/mL receiving HBV-active ART for 1 year or more (aHR, 0.42 [0.24-0.73]). In addition, a dose-response relationship was observed between the duration of suppression and this protective effect.

Dr. Nina Kim acknowledged that a key limitation of the study was inconsistent monitoring of HBV DNA level while patients were on treatment. Furthermore, given the demographics of the cohort, these results may not be generalizable outside of North America.

“Our study was the first to show that any level of HBV viremia using 200 as a threshold of detection was associated with HCC risk in a large regionally diverse cohort of adults outside of Asia,” Dr. Kim said. “To gain maximal protective benefit from antiviral therapy for HCC prevention, sustained and ideally uninterrupted suppression of HBV may be necessary over years.”

“HIV/HBV coinfected patients can take much longer than a year to achieve less than 200 copies on HBV DNA due to their baseline levels, but we still don’t know if HBV therapy intensification could hasten this process,” said moderator Robert T. Schooley, MD, of the University of California, San Diego.

Dr. Kim disclosed no conflicts of interest. The study was supported by multiple sources, including the National Institutes of Health, the Centers for Disease Control and Prevention, and the National Cancer Institute.

Any level of hepatitis B virus (HBV) viremia was associated with increased hepatocellular carcinoma (HCC) risk in adults with HIV/HBV coinfection, according to new research presented at the Conference on Retroviruses and Opportunistic Infections (Abstract 136).

sarathsasidharan/Thinkstock

“Chronic HBV coinfection is common among people with HIV, but the determinants of HBV-associated HCC are not well characterized,” said presenter H. Nina Kim MD, MSc, of the University of Washington, Seattle. “We sought to identify factors that contribute to HCC development in persons with HIV/HBV coinfection to guide early detection and prevention measures.”

The researchers conducted a longitudinal cohort study within the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD), a collaboration of single-site and multisite cohorts throughout the United States and Canada; 22 cohorts from NA-ACCORD were included in the analysis.

Potential HIV and HBV risk factors were examined, including viremia and CD4 percentage, as well as HBV DNA levels. Traditional risk factors for liver disease progression, including age, sex, and heavy alcohol use, were also assessed.

Eligible patients were 18 years of age or older who were followed for at least 6 months, had evidence of chronic HBV, and had HIV RNA or CD4+ cell measurement during this period. Persons with prevalent HCC at baseline were excluded.

The primary outcome was first occurrence of HCC, which was adjudicated by medical chart review and/or cancer registry. Multivariable Cox regression was used to determine adjusted hazard ratios of risk factors.
 

Results

Among 9,383 HIV/HBV-coinfected individuals identified, 8,354 (89%) were included in the analysis. The median age of participants was 43 years and 93.1% were male. Heavy alcohol use (35.3%) and chronic hepatitis C virus (HCV) coinfection (21.6%) were common among participants.

Among 8,354 eligible participants, 115 developed HCC over a median 6.9 years of follow-up (incidence rate, 1.8 events per 1,000 person-years; 95% confidence interval [CI], 1.5-2.1).

Independent risk factors for HCC were chronic HCV coinfection (adjusted hazard ratio [aHR], 1.60 [95% confidence interval, 1.07-2.39]), age 40 years and older (aHR, 2.14 [1.36-3.37]), and heavy alcohol use (aHR, 1.51 [1.03-2.21]); however, time-updated CD4+ percentage less than 14% (aHR, 1.03 [0.56-1.90]) and time-updated HIV RNA level over 500 copies/mL (aHR, 0.88 [0.55-1.41]) were not associated with HCC risk.

In a second model, among 3,054 patients who had HBV DNA measured, the risk of HCC was higher with HBV DNA levels greater than 200 IU/mL (aHR, 2.70 [1.23-5.93]), and the risk was particularly elevated at levels greater than 200,000 IU/mL (aHR, 4.34 [1.72-10.94]).

The researchers also found that the risk of HCC was significantly lower in patients with HBV DNA suppression less than 200 IU/mL receiving HBV-active ART for 1 year or more (aHR, 0.42 [0.24-0.73]). In addition, a dose-response relationship was observed between the duration of suppression and this protective effect.

Dr. Nina Kim acknowledged that a key limitation of the study was inconsistent monitoring of HBV DNA level while patients were on treatment. Furthermore, given the demographics of the cohort, these results may not be generalizable outside of North America.

“Our study was the first to show that any level of HBV viremia using 200 as a threshold of detection was associated with HCC risk in a large regionally diverse cohort of adults outside of Asia,” Dr. Kim said. “To gain maximal protective benefit from antiviral therapy for HCC prevention, sustained and ideally uninterrupted suppression of HBV may be necessary over years.”

“HIV/HBV coinfected patients can take much longer than a year to achieve less than 200 copies on HBV DNA due to their baseline levels, but we still don’t know if HBV therapy intensification could hasten this process,” said moderator Robert T. Schooley, MD, of the University of California, San Diego.

Dr. Kim disclosed no conflicts of interest. The study was supported by multiple sources, including the National Institutes of Health, the Centers for Disease Control and Prevention, and the National Cancer Institute.

Any level of hepatitis B virus (HBV) viremia was associated with increased hepatocellular carcinoma (HCC) risk in adults with HIV/HBV coinfection, according to new research presented at the Conference on Retroviruses and Opportunistic Infections (Abstract 136).

sarathsasidharan/Thinkstock

“Chronic HBV coinfection is common among people with HIV, but the determinants of HBV-associated HCC are not well characterized,” said presenter H. Nina Kim MD, MSc, of the University of Washington, Seattle. “We sought to identify factors that contribute to HCC development in persons with HIV/HBV coinfection to guide early detection and prevention measures.”

The researchers conducted a longitudinal cohort study within the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD), a collaboration of single-site and multisite cohorts throughout the United States and Canada; 22 cohorts from NA-ACCORD were included in the analysis.

Potential HIV and HBV risk factors were examined, including viremia and CD4 percentage, as well as HBV DNA levels. Traditional risk factors for liver disease progression, including age, sex, and heavy alcohol use, were also assessed.

Eligible patients were 18 years of age or older who were followed for at least 6 months, had evidence of chronic HBV, and had HIV RNA or CD4+ cell measurement during this period. Persons with prevalent HCC at baseline were excluded.

The primary outcome was first occurrence of HCC, which was adjudicated by medical chart review and/or cancer registry. Multivariable Cox regression was used to determine adjusted hazard ratios of risk factors.
 

Results

Among 9,383 HIV/HBV-coinfected individuals identified, 8,354 (89%) were included in the analysis. The median age of participants was 43 years and 93.1% were male. Heavy alcohol use (35.3%) and chronic hepatitis C virus (HCV) coinfection (21.6%) were common among participants.

Among 8,354 eligible participants, 115 developed HCC over a median 6.9 years of follow-up (incidence rate, 1.8 events per 1,000 person-years; 95% confidence interval [CI], 1.5-2.1).

Independent risk factors for HCC were chronic HCV coinfection (adjusted hazard ratio [aHR], 1.60 [95% confidence interval, 1.07-2.39]), age 40 years and older (aHR, 2.14 [1.36-3.37]), and heavy alcohol use (aHR, 1.51 [1.03-2.21]); however, time-updated CD4+ percentage less than 14% (aHR, 1.03 [0.56-1.90]) and time-updated HIV RNA level over 500 copies/mL (aHR, 0.88 [0.55-1.41]) were not associated with HCC risk.

In a second model, among 3,054 patients who had HBV DNA measured, the risk of HCC was higher with HBV DNA levels greater than 200 IU/mL (aHR, 2.70 [1.23-5.93]), and the risk was particularly elevated at levels greater than 200,000 IU/mL (aHR, 4.34 [1.72-10.94]).

The researchers also found that the risk of HCC was significantly lower in patients with HBV DNA suppression less than 200 IU/mL receiving HBV-active ART for 1 year or more (aHR, 0.42 [0.24-0.73]). In addition, a dose-response relationship was observed between the duration of suppression and this protective effect.

Dr. Nina Kim acknowledged that a key limitation of the study was inconsistent monitoring of HBV DNA level while patients were on treatment. Furthermore, given the demographics of the cohort, these results may not be generalizable outside of North America.

“Our study was the first to show that any level of HBV viremia using 200 as a threshold of detection was associated with HCC risk in a large regionally diverse cohort of adults outside of Asia,” Dr. Kim said. “To gain maximal protective benefit from antiviral therapy for HCC prevention, sustained and ideally uninterrupted suppression of HBV may be necessary over years.”

“HIV/HBV coinfected patients can take much longer than a year to achieve less than 200 copies on HBV DNA due to their baseline levels, but we still don’t know if HBV therapy intensification could hasten this process,” said moderator Robert T. Schooley, MD, of the University of California, San Diego.

Dr. Kim disclosed no conflicts of interest. The study was supported by multiple sources, including the National Institutes of Health, the Centers for Disease Control and Prevention, and the National Cancer Institute.

Despite recent advances in the diagnosis, treatment, and prevention of pediatric tuberculosis in children living with HIV (CLHIV) and HIV-exposed uninfected children (HEU), several unmet needs remain, including studies evaluating the feasibility of shortened TB treatment regimens.

“Children living with HIV contribute disproportionately to pediatric TB mortality rates, accounting for 16% of child TB deaths, and many cases are underdiagnosed and underreported,” said Nicole Salazar-Austin, MD, of Johns Hopkins University in Baltimore. She provided an update on pediatric TB prevention and treatment during an educational symposium at this year’s virtual Conference on Retroviruses & Opportunistic Infections.

Dr. Salazar-Austin summarized current diagnostics for pediatric TB and reviewed options for the prevention and treatment of TB in CLHIV and HEU.
 

TB and CLHIV

Presently, TB is the most common opportunistic infection among CLHIV, and those with severe immune suppression have a fivefold greater risk of TB disease. While antiretroviral therapy (ART) is highly protective against TB disease in CLHIV, only about 50% of eligible children receive ART.

Dr. Salazar-Austin explained that many individuals with TB/HIV coinfection are unaware of their coinfection and not receiving treatment. Despite recommendations, TB preventive therapy is poorly implemented in CLHIV, especially in high-burden settings.
 

Pediatric TB diagnosis

Smear microscopy, culture, and Xpert MTB/RIF Ultra are the main diagnostic modalities for pediatric TB. The Xpert MTB/RIF test is an automated PCR-based assay that simultaneously and rapidly detects Mycobacterium tuberculosis complex and resistance to rifampin. The test is currently recommended by the World Health Organization as the initial diagnostic method for presumptive TB cases in both adults and children.

However, under optimal conditions, only 40% of TB cases will be detected. This is in part due to limited implementation of sputum collection procedures, but recent evidence has shown that collection of multiple specimens improves sensitivity for both culture and Xpert MTB/RIF Ultra across all specimen types, Dr. Salazar-Austin explained.

In 2020, the WHO endorsed the use of stool samples for the diagnosis of pediatric pulmonary TB. Stool Xpert is an emerging alternative, noninvasive method for ruling in pediatric TB disease, and has shown sensitivity and specificity similar to that of Xpert MTB/RIF Ultra.

“TB diagnostics have limited sensitivity in children, and efforts are ongoing to maximize current diagnostics, but new diagnostics are needed,” said Dr. Salazar-Austin.
 

Pediatric TB treatment

Despite the high frequency of TB as an opportunistic infection in CLHIV, current data on co-treatment strategies are limited.

Dolutegravir-based regimens are the preferred first-line regimen for CLHIV. In June 2020, the Food and Drug Administration approved the dispersible dolutegravir tablet, and it is expected to become widely available in 2021.

In children with TB/HIV coinfection who receive dolutegravir and rifampicin, dolutegravir is typically dosed twice daily because of a known drug interaction, based on data from the ODYSSEY study. The WHO recommendations for treatment of pediatric TB/HIV coinfection were recently updated to reflect twice-daily dosing of dolutegravir.

Despite these new recommendations, data are currently limited, and observational pharmacokinetic studies evaluating twice daily dolutegravir with TB treatment in young children are needed.

“More work is needed to evaluate the drug-drug interactions and proper dosing of rifamycins with dolutegravir for the treatment and prevention of TB in CLHIV,” Dr. Salazar-Austin said.

Based on data from TBTC Study 31/ACTG A5349, high-dose rifapentine (a rifamycin) with moxifloxacin (a fluoroquinolone) was noninferior to rifapentine alone in newly diagnosed, culture positive, drug-susceptible TB in children 12 years and older.

Whether rifapentine and moxifloxacin (RPT-Mox) can be used in children under 12 years remains unknown, but future studies may help answer this question, Dr. Salazar-Austin noted. The FDA has restricted the use of fluoroquinolones in children because of a possible effect on cartilage development, she explained.

Furthermore, recent data from the SHINE trial suggested that shortened treatment regimens may hold promise for children with TB.

“While shortened TB treatment regimens hold promise, much work needs to be done in children to implement RPT-Mox, but the results from SHINE can be implemented rapidly,” Dr. Salazar-Austin said.

Dr. Salazar-Austin disclosed no conflicts of interest. The presentation was funded by NICHD, UNITAID, Fogarty Institute, and the IMPAACT network.

Despite recent advances in the diagnosis, treatment, and prevention of pediatric tuberculosis in children living with HIV (CLHIV) and HIV-exposed uninfected children (HEU), several unmet needs remain, including studies evaluating the feasibility of shortened TB treatment regimens.

“Children living with HIV contribute disproportionately to pediatric TB mortality rates, accounting for 16% of child TB deaths, and many cases are underdiagnosed and underreported,” said Nicole Salazar-Austin, MD, of Johns Hopkins University in Baltimore. She provided an update on pediatric TB prevention and treatment during an educational symposium at this year’s virtual Conference on Retroviruses & Opportunistic Infections.

Dr. Salazar-Austin summarized current diagnostics for pediatric TB and reviewed options for the prevention and treatment of TB in CLHIV and HEU.
 

TB and CLHIV

Presently, TB is the most common opportunistic infection among CLHIV, and those with severe immune suppression have a fivefold greater risk of TB disease. While antiretroviral therapy (ART) is highly protective against TB disease in CLHIV, only about 50% of eligible children receive ART.

Dr. Salazar-Austin explained that many individuals with TB/HIV coinfection are unaware of their coinfection and not receiving treatment. Despite recommendations, TB preventive therapy is poorly implemented in CLHIV, especially in high-burden settings.
 

Pediatric TB diagnosis

Smear microscopy, culture, and Xpert MTB/RIF Ultra are the main diagnostic modalities for pediatric TB. The Xpert MTB/RIF test is an automated PCR-based assay that simultaneously and rapidly detects Mycobacterium tuberculosis complex and resistance to rifampin. The test is currently recommended by the World Health Organization as the initial diagnostic method for presumptive TB cases in both adults and children.

However, under optimal conditions, only 40% of TB cases will be detected. This is in part due to limited implementation of sputum collection procedures, but recent evidence has shown that collection of multiple specimens improves sensitivity for both culture and Xpert MTB/RIF Ultra across all specimen types, Dr. Salazar-Austin explained.

In 2020, the WHO endorsed the use of stool samples for the diagnosis of pediatric pulmonary TB. Stool Xpert is an emerging alternative, noninvasive method for ruling in pediatric TB disease, and has shown sensitivity and specificity similar to that of Xpert MTB/RIF Ultra.

“TB diagnostics have limited sensitivity in children, and efforts are ongoing to maximize current diagnostics, but new diagnostics are needed,” said Dr. Salazar-Austin.
 

Pediatric TB treatment

Despite the high frequency of TB as an opportunistic infection in CLHIV, current data on co-treatment strategies are limited.

Dolutegravir-based regimens are the preferred first-line regimen for CLHIV. In June 2020, the Food and Drug Administration approved the dispersible dolutegravir tablet, and it is expected to become widely available in 2021.

In children with TB/HIV coinfection who receive dolutegravir and rifampicin, dolutegravir is typically dosed twice daily because of a known drug interaction, based on data from the ODYSSEY study. The WHO recommendations for treatment of pediatric TB/HIV coinfection were recently updated to reflect twice-daily dosing of dolutegravir.

Despite these new recommendations, data are currently limited, and observational pharmacokinetic studies evaluating twice daily dolutegravir with TB treatment in young children are needed.

“More work is needed to evaluate the drug-drug interactions and proper dosing of rifamycins with dolutegravir for the treatment and prevention of TB in CLHIV,” Dr. Salazar-Austin said.

Based on data from TBTC Study 31/ACTG A5349, high-dose rifapentine (a rifamycin) with moxifloxacin (a fluoroquinolone) was noninferior to rifapentine alone in newly diagnosed, culture positive, drug-susceptible TB in children 12 years and older.

Whether rifapentine and moxifloxacin (RPT-Mox) can be used in children under 12 years remains unknown, but future studies may help answer this question, Dr. Salazar-Austin noted. The FDA has restricted the use of fluoroquinolones in children because of a possible effect on cartilage development, she explained.

Furthermore, recent data from the SHINE trial suggested that shortened treatment regimens may hold promise for children with TB.

“While shortened TB treatment regimens hold promise, much work needs to be done in children to implement RPT-Mox, but the results from SHINE can be implemented rapidly,” Dr. Salazar-Austin said.

Dr. Salazar-Austin disclosed no conflicts of interest. The presentation was funded by NICHD, UNITAID, Fogarty Institute, and the IMPAACT network.

Despite recent advances in the diagnosis, treatment, and prevention of pediatric tuberculosis in children living with HIV (CLHIV) and HIV-exposed uninfected children (HEU), several unmet needs remain, including studies evaluating the feasibility of shortened TB treatment regimens.

“Children living with HIV contribute disproportionately to pediatric TB mortality rates, accounting for 16% of child TB deaths, and many cases are underdiagnosed and underreported,” said Nicole Salazar-Austin, MD, of Johns Hopkins University in Baltimore. She provided an update on pediatric TB prevention and treatment during an educational symposium at this year’s virtual Conference on Retroviruses & Opportunistic Infections.

Dr. Salazar-Austin summarized current diagnostics for pediatric TB and reviewed options for the prevention and treatment of TB in CLHIV and HEU.
 

TB and CLHIV

Presently, TB is the most common opportunistic infection among CLHIV, and those with severe immune suppression have a fivefold greater risk of TB disease. While antiretroviral therapy (ART) is highly protective against TB disease in CLHIV, only about 50% of eligible children receive ART.

Dr. Salazar-Austin explained that many individuals with TB/HIV coinfection are unaware of their coinfection and not receiving treatment. Despite recommendations, TB preventive therapy is poorly implemented in CLHIV, especially in high-burden settings.
 

Pediatric TB diagnosis

Smear microscopy, culture, and Xpert MTB/RIF Ultra are the main diagnostic modalities for pediatric TB. The Xpert MTB/RIF test is an automated PCR-based assay that simultaneously and rapidly detects Mycobacterium tuberculosis complex and resistance to rifampin. The test is currently recommended by the World Health Organization as the initial diagnostic method for presumptive TB cases in both adults and children.

However, under optimal conditions, only 40% of TB cases will be detected. This is in part due to limited implementation of sputum collection procedures, but recent evidence has shown that collection of multiple specimens improves sensitivity for both culture and Xpert MTB/RIF Ultra across all specimen types, Dr. Salazar-Austin explained.

In 2020, the WHO endorsed the use of stool samples for the diagnosis of pediatric pulmonary TB. Stool Xpert is an emerging alternative, noninvasive method for ruling in pediatric TB disease, and has shown sensitivity and specificity similar to that of Xpert MTB/RIF Ultra.

“TB diagnostics have limited sensitivity in children, and efforts are ongoing to maximize current diagnostics, but new diagnostics are needed,” said Dr. Salazar-Austin.
 

Pediatric TB treatment

Despite the high frequency of TB as an opportunistic infection in CLHIV, current data on co-treatment strategies are limited.

Dolutegravir-based regimens are the preferred first-line regimen for CLHIV. In June 2020, the Food and Drug Administration approved the dispersible dolutegravir tablet, and it is expected to become widely available in 2021.

In children with TB/HIV coinfection who receive dolutegravir and rifampicin, dolutegravir is typically dosed twice daily because of a known drug interaction, based on data from the ODYSSEY study. The WHO recommendations for treatment of pediatric TB/HIV coinfection were recently updated to reflect twice-daily dosing of dolutegravir.

Despite these new recommendations, data are currently limited, and observational pharmacokinetic studies evaluating twice daily dolutegravir with TB treatment in young children are needed.

“More work is needed to evaluate the drug-drug interactions and proper dosing of rifamycins with dolutegravir for the treatment and prevention of TB in CLHIV,” Dr. Salazar-Austin said.

Based on data from TBTC Study 31/ACTG A5349, high-dose rifapentine (a rifamycin) with moxifloxacin (a fluoroquinolone) was noninferior to rifapentine alone in newly diagnosed, culture positive, drug-susceptible TB in children 12 years and older.

Whether rifapentine and moxifloxacin (RPT-Mox) can be used in children under 12 years remains unknown, but future studies may help answer this question, Dr. Salazar-Austin noted. The FDA has restricted the use of fluoroquinolones in children because of a possible effect on cartilage development, she explained.

Furthermore, recent data from the SHINE trial suggested that shortened treatment regimens may hold promise for children with TB.

“While shortened TB treatment regimens hold promise, much work needs to be done in children to implement RPT-Mox, but the results from SHINE can be implemented rapidly,” Dr. Salazar-Austin said.

Dr. Salazar-Austin disclosed no conflicts of interest. The presentation was funded by NICHD, UNITAID, Fogarty Institute, and the IMPAACT network.

Long-acting injectable (LAI) drug formulations represent a promising new strategy for the prevention and treatment of tuberculosis in women and children, according to an online presentation at the Conference on Retroviruses & Opportunistic Infections, held virtually.

“As a delivery strategy, LAIs hold the potential to unlock a vast chemical space of lipophilic compounds with very potent anti-TB activity that would otherwise not be developed due to poor predicted oral bioavailability,” explained presenter Eric Nuermberger, MD.

He summarized current preventive treatment options for TB and reviewed the potential impact of LAI formulations on TB therapy. In addition, he identified key challenges for future LAI development and proposed a new development path for clinical implementation.
 

Current TB preventive therapies

Despite widespread availability, the uptake of TB preventive therapy is poor and currently lags behind global targets. One key barrier to widespread uptake is the long duration of treatment, which may hinder patient adherence to therapy.

While shorter preventive regimens, such as 1 month of daily isoniazid plus rifapentine, show similar efficacy and higher completion rates, further shortening of therapy and reducing clinic visits are the most direct methods to increase adherence and treatment completion rates, Dr. Nuermberger said.
 

LAI drugs

LAI drug formulations allow for slow release of suitable drugs from a depot injected subcutaneously or intramuscularly.

The goal of LAI formulations is to free patients from the daily burden of oral administration. Other potential benefits include better adherence and efficacy, drug exposure, and the potential to overcome intrinsic poor oral bioavailability by bypassing the GI tract entirely.

Potential indications for LAIs include treatment of latent tuberculosis infection (LTBI), and as continuous therapy in people living with HIV in high-burden settings. There is also potential for treating younger children, such as household contacts, who have difficulty taking oral medications.

“We’ve already seen LAIs revolutionize other areas, such as psychiatry and contraception, and we appear to have another revolution in HIV prevention and treatment,” Dr. Nuermberger explained.

Not all existing TB drugs are suitable for LAI formulations, but drugs such as rifapentine, rifabutin, delamanid, and bedaquiline, show more promise than isoniazid or rifampin because of their physiochemical composition. Of all, bedaquiline may offer the best profile for LAI formulation, Dr. Nuermberger said.

Early proof-of-concept in vivo studies have shown potential use of LAI bedaquiline for TB prevention in both drug-sensitive and drug-resistant TB contacts. Translational PK modeling and simulation predicted that a 1-g intramuscular injection of LAI bedaquiline could maintain therapeutic plasma concentrations in humans for greater than 1 month.

Dr. Nuermberger noted that novel diarylquinoline-based therapies, currently in phase 1 studies, may be even better candidates for LAI-based TB preventive therapy. Early data suggests these compounds may be 10-20 times more potent and have a lower CV risk profile than that of bedaquiline.
 

Considerations for development and implementation

“Despite the promising potential of long-acting injectables for TB, we are still in the very early stages,” said Dr. Nuermberger.

Ensuring and optimizing acceptance of LAI formulations, especially in at-risk populations, will be very important, he explained. Early involvement of children and pregnant women in studies of who may benefit most from LAI drugs will also be essential.

Other important considerations include cost-effectiveness, particularly in at-risk and vulnerable populations. Furthermore, new dedicated research and development programs are needed to continue to develop more drug candidates suitable for LAI.

“Long-acting formulations hold enormous promise to be transformative for combating TB, through simplification of delivery and overcoming issues of adherence that can compromise success of current interventions,” said Andrew Owen, PhD, of the University of Liverpool (England).

“The ability to deliver an entire course of drug in a single visit promises to ensure missed doses don’t compromise outcomes or place unnecessary selective pressure in favor of drug resistance,” Dr. Owen said.

“Recent studies showing the value of one-month oral treatment regimens for LTBI make long-acting formulations seem more realistic and drugs such as long-acting bedaquiline put a one-shot regimen within reach,” Charles W. Flexner, MD, of Johns Hopkins University, Baltimore, said in an interview.

While no LAIs have been approved for TB, Dr. Nuermberger was optimistic that the recent success of LAI formulations for HIV treatment and prevention will catalyze further efforts in the TB landscape.

Dr. Nuermberger disclosed research support from Janssen Pharmaceuticals, TB Alliance, and the Gates Medical Research Institute. The presentation was sponsored by Janssen Pharmaceuticals, Johns Hopkins CFAR, NIH, Unitaid, and the TB Alliance.

Long-acting injectable (LAI) drug formulations represent a promising new strategy for the prevention and treatment of tuberculosis in women and children, according to an online presentation at the Conference on Retroviruses & Opportunistic Infections, held virtually.

“As a delivery strategy, LAIs hold the potential to unlock a vast chemical space of lipophilic compounds with very potent anti-TB activity that would otherwise not be developed due to poor predicted oral bioavailability,” explained presenter Eric Nuermberger, MD.

He summarized current preventive treatment options for TB and reviewed the potential impact of LAI formulations on TB therapy. In addition, he identified key challenges for future LAI development and proposed a new development path for clinical implementation.
 

Current TB preventive therapies

Despite widespread availability, the uptake of TB preventive therapy is poor and currently lags behind global targets. One key barrier to widespread uptake is the long duration of treatment, which may hinder patient adherence to therapy.

While shorter preventive regimens, such as 1 month of daily isoniazid plus rifapentine, show similar efficacy and higher completion rates, further shortening of therapy and reducing clinic visits are the most direct methods to increase adherence and treatment completion rates, Dr. Nuermberger said.
 

LAI drugs

LAI drug formulations allow for slow release of suitable drugs from a depot injected subcutaneously or intramuscularly.

The goal of LAI formulations is to free patients from the daily burden of oral administration. Other potential benefits include better adherence and efficacy, drug exposure, and the potential to overcome intrinsic poor oral bioavailability by bypassing the GI tract entirely.

Potential indications for LAIs include treatment of latent tuberculosis infection (LTBI), and as continuous therapy in people living with HIV in high-burden settings. There is also potential for treating younger children, such as household contacts, who have difficulty taking oral medications.

“We’ve already seen LAIs revolutionize other areas, such as psychiatry and contraception, and we appear to have another revolution in HIV prevention and treatment,” Dr. Nuermberger explained.

Not all existing TB drugs are suitable for LAI formulations, but drugs such as rifapentine, rifabutin, delamanid, and bedaquiline, show more promise than isoniazid or rifampin because of their physiochemical composition. Of all, bedaquiline may offer the best profile for LAI formulation, Dr. Nuermberger said.

Early proof-of-concept in vivo studies have shown potential use of LAI bedaquiline for TB prevention in both drug-sensitive and drug-resistant TB contacts. Translational PK modeling and simulation predicted that a 1-g intramuscular injection of LAI bedaquiline could maintain therapeutic plasma concentrations in humans for greater than 1 month.

Dr. Nuermberger noted that novel diarylquinoline-based therapies, currently in phase 1 studies, may be even better candidates for LAI-based TB preventive therapy. Early data suggests these compounds may be 10-20 times more potent and have a lower CV risk profile than that of bedaquiline.
 

Considerations for development and implementation

“Despite the promising potential of long-acting injectables for TB, we are still in the very early stages,” said Dr. Nuermberger.

Ensuring and optimizing acceptance of LAI formulations, especially in at-risk populations, will be very important, he explained. Early involvement of children and pregnant women in studies of who may benefit most from LAI drugs will also be essential.

Other important considerations include cost-effectiveness, particularly in at-risk and vulnerable populations. Furthermore, new dedicated research and development programs are needed to continue to develop more drug candidates suitable for LAI.

“Long-acting formulations hold enormous promise to be transformative for combating TB, through simplification of delivery and overcoming issues of adherence that can compromise success of current interventions,” said Andrew Owen, PhD, of the University of Liverpool (England).

“The ability to deliver an entire course of drug in a single visit promises to ensure missed doses don’t compromise outcomes or place unnecessary selective pressure in favor of drug resistance,” Dr. Owen said.

“Recent studies showing the value of one-month oral treatment regimens for LTBI make long-acting formulations seem more realistic and drugs such as long-acting bedaquiline put a one-shot regimen within reach,” Charles W. Flexner, MD, of Johns Hopkins University, Baltimore, said in an interview.

While no LAIs have been approved for TB, Dr. Nuermberger was optimistic that the recent success of LAI formulations for HIV treatment and prevention will catalyze further efforts in the TB landscape.

Dr. Nuermberger disclosed research support from Janssen Pharmaceuticals, TB Alliance, and the Gates Medical Research Institute. The presentation was sponsored by Janssen Pharmaceuticals, Johns Hopkins CFAR, NIH, Unitaid, and the TB Alliance.

Long-acting injectable (LAI) drug formulations represent a promising new strategy for the prevention and treatment of tuberculosis in women and children, according to an online presentation at the Conference on Retroviruses & Opportunistic Infections, held virtually.

“As a delivery strategy, LAIs hold the potential to unlock a vast chemical space of lipophilic compounds with very potent anti-TB activity that would otherwise not be developed due to poor predicted oral bioavailability,” explained presenter Eric Nuermberger, MD.

He summarized current preventive treatment options for TB and reviewed the potential impact of LAI formulations on TB therapy. In addition, he identified key challenges for future LAI development and proposed a new development path for clinical implementation.
 

Current TB preventive therapies

Despite widespread availability, the uptake of TB preventive therapy is poor and currently lags behind global targets. One key barrier to widespread uptake is the long duration of treatment, which may hinder patient adherence to therapy.

While shorter preventive regimens, such as 1 month of daily isoniazid plus rifapentine, show similar efficacy and higher completion rates, further shortening of therapy and reducing clinic visits are the most direct methods to increase adherence and treatment completion rates, Dr. Nuermberger said.
 

LAI drugs

LAI drug formulations allow for slow release of suitable drugs from a depot injected subcutaneously or intramuscularly.

The goal of LAI formulations is to free patients from the daily burden of oral administration. Other potential benefits include better adherence and efficacy, drug exposure, and the potential to overcome intrinsic poor oral bioavailability by bypassing the GI tract entirely.

Potential indications for LAIs include treatment of latent tuberculosis infection (LTBI), and as continuous therapy in people living with HIV in high-burden settings. There is also potential for treating younger children, such as household contacts, who have difficulty taking oral medications.

“We’ve already seen LAIs revolutionize other areas, such as psychiatry and contraception, and we appear to have another revolution in HIV prevention and treatment,” Dr. Nuermberger explained.

Not all existing TB drugs are suitable for LAI formulations, but drugs such as rifapentine, rifabutin, delamanid, and bedaquiline, show more promise than isoniazid or rifampin because of their physiochemical composition. Of all, bedaquiline may offer the best profile for LAI formulation, Dr. Nuermberger said.

Early proof-of-concept in vivo studies have shown potential use of LAI bedaquiline for TB prevention in both drug-sensitive and drug-resistant TB contacts. Translational PK modeling and simulation predicted that a 1-g intramuscular injection of LAI bedaquiline could maintain therapeutic plasma concentrations in humans for greater than 1 month.

Dr. Nuermberger noted that novel diarylquinoline-based therapies, currently in phase 1 studies, may be even better candidates for LAI-based TB preventive therapy. Early data suggests these compounds may be 10-20 times more potent and have a lower CV risk profile than that of bedaquiline.
 

Considerations for development and implementation

“Despite the promising potential of long-acting injectables for TB, we are still in the very early stages,” said Dr. Nuermberger.

Ensuring and optimizing acceptance of LAI formulations, especially in at-risk populations, will be very important, he explained. Early involvement of children and pregnant women in studies of who may benefit most from LAI drugs will also be essential.

Other important considerations include cost-effectiveness, particularly in at-risk and vulnerable populations. Furthermore, new dedicated research and development programs are needed to continue to develop more drug candidates suitable for LAI.

“Long-acting formulations hold enormous promise to be transformative for combating TB, through simplification of delivery and overcoming issues of adherence that can compromise success of current interventions,” said Andrew Owen, PhD, of the University of Liverpool (England).

“The ability to deliver an entire course of drug in a single visit promises to ensure missed doses don’t compromise outcomes or place unnecessary selective pressure in favor of drug resistance,” Dr. Owen said.

“Recent studies showing the value of one-month oral treatment regimens for LTBI make long-acting formulations seem more realistic and drugs such as long-acting bedaquiline put a one-shot regimen within reach,” Charles W. Flexner, MD, of Johns Hopkins University, Baltimore, said in an interview.

While no LAIs have been approved for TB, Dr. Nuermberger was optimistic that the recent success of LAI formulations for HIV treatment and prevention will catalyze further efforts in the TB landscape.

Dr. Nuermberger disclosed research support from Janssen Pharmaceuticals, TB Alliance, and the Gates Medical Research Institute. The presentation was sponsored by Janssen Pharmaceuticals, Johns Hopkins CFAR, NIH, Unitaid, and the TB Alliance.

A single pill of the investigational drug molnupiravir taken twice a day for 5 days eliminated SARS-CoV-2 from the nasopharynx of 49 participants.

That led Carlos del Rio, MD, distinguished professor of medicine at Emory University, Atlanta, to suggest a future in which a drug like molnupiravir could be taken in the first few days of symptoms to prevent severe disease, similar to Tamiflu for influenza.

“I think it’s critically important,” he said of the data. Emory University was involved in the trial of molnupiravir but Dr. del Rio was not part of that team. “This drug offers the first antiviral oral drug that then could be used in an outpatient setting.”

Still, Dr. del Rio said it’s too soon to call this particular drug the breakthrough clinicians need to keep people out of the ICU. “It has the potential to be practice changing; it’s not practice changing at the moment.”

Wendy Painter, MD, of Ridgeback Biotherapeutics, who presented the data at the Conference on Retroviruses and Opportunistic Infections, agreed. While the data are promising, “We will need to see if people get better from actual illness” to assess the real value of the drug in clinical care.

“That’s a phase 3 objective we’ll need to prove,” she said in an interview.

Phase 2/3 efficacy and safety studies of the drug are now underway in hospitalized and nonhospitalized patients.

In a brief prerecorded presentation of the data, Dr. Painter laid out what researchers know so far: Preclinical studies suggest that molnupiravir is effective against a number of viruses, including coronaviruses and specifically SARS-CoV-2. It prevents a virus from replicating by inducing viral error catastrophe (Proc Natl Acad Sci U S A. 2002 Oct 15;99[21]:13374-6) – essentially overloading the virus with replication and mutation until the virus burns itself out and can’t produce replicable copies.

In this phase 2a, randomized, double-blind, controlled trial, researchers recruited 202 adults who were treated at an outpatient clinic with fever or other symptoms of a respiratory virus and confirmed SARS-CoV-2 infection by day 4. Participants were randomly assigned to three different groups: 200 mg of molnupiravir, 400 mg, or 800 mg. The 200-mg arm was matched 1:1 with a placebo-controlled group, and the other two groups had three participants in the active group for every one control.

Participants took the pills twice daily for 5 days, and then were followed for a total of 28 days to monitor for complications or adverse events. At days 3, 5, 7, 14, and 28, researchers also took nasopharyngeal swabs for polymerase chain reaction tests, to sequence the virus, and to grow cultures of SARS-CoV-2 to see if the virus that’s present is actually capable of infecting others.

Notably, the pills do not have to be refrigerated at any point in the process, alleviating the cold-chain challenges that have plagued vaccines.

“There’s an urgent need for an easily produced, transported, stored, and administered antiviral drug against SARS-CoV-2,” Dr. Painter said.

Of the 202 people recruited, 182 had swabs that could be evaluated, of which 78 showed infection at baseline. The results are based on labs of those 78 participants.

By day 3, 28% of patients in the placebo arm had SARS-CoV-2 in their nasopharynx, compared with 20.4% of patients receiving any dose of molnupiravir. But by day 5, none of the participants receiving the active drug had evidence of SARS-CoV-2 in their nasopharynx. In comparison, 24% of people in the placebo arm still had detectable virus.

Halfway through the treatment course, differences in the presence of infectious virus were already evident. By day 3 of the 5-day course, 36.4% of participants in the 200-mg group had detectable virus in the nasopharynx, compared with 21% in the 400-mg group and just 12.5% in the 800-mg group. And although the reduction in SARS-CoV-2 was noticeable in the 200-mg and the 400-mg arms, it was only statistically significant in the 800-mg arm.

In contrast, by the end of the 5 days in the placebo groups, infectious virus varied from 18.2% in the 200-mg placebo group to 30% in the 800-mg group. This points out the variability of the disease course of SARS-CoV-2.

“You just don’t know” which infections will lead to serious disease, Dr. Painter said in an interview. “And don’t you wish we did?”

Seven participants discontinued treatment, though only four experienced adverse events. Three of those discontinued the trial because of adverse events. The study is still blinded, so it’s unclear what those events were, but Dr. Painter said that they were not thought to be related to the study drug.

The bottom line, said Dr. Painter, was that people treated with molnupiravir had starkly different outcomes in lab measures during the study.

“An average of 10 days after symptom onset, 24% of placebo patients remained culture positive” for SARS-CoV-2 – meaning there wasn’t just virus in the nasopharynx, but it was capable of replicating, Dr. Painter said. “In contrast, no infectious virus could be recovered at study day 5 in any molnupiravir-treated patients.”

A version of this article first appeared on Medscape.com.

A single pill of the investigational drug molnupiravir taken twice a day for 5 days eliminated SARS-CoV-2 from the nasopharynx of 49 participants.

That led Carlos del Rio, MD, distinguished professor of medicine at Emory University, Atlanta, to suggest a future in which a drug like molnupiravir could be taken in the first few days of symptoms to prevent severe disease, similar to Tamiflu for influenza.

“I think it’s critically important,” he said of the data. Emory University was involved in the trial of molnupiravir but Dr. del Rio was not part of that team. “This drug offers the first antiviral oral drug that then could be used in an outpatient setting.”

Still, Dr. del Rio said it’s too soon to call this particular drug the breakthrough clinicians need to keep people out of the ICU. “It has the potential to be practice changing; it’s not practice changing at the moment.”

Wendy Painter, MD, of Ridgeback Biotherapeutics, who presented the data at the Conference on Retroviruses and Opportunistic Infections, agreed. While the data are promising, “We will need to see if people get better from actual illness” to assess the real value of the drug in clinical care.

“That’s a phase 3 objective we’ll need to prove,” she said in an interview.

Phase 2/3 efficacy and safety studies of the drug are now underway in hospitalized and nonhospitalized patients.

In a brief prerecorded presentation of the data, Dr. Painter laid out what researchers know so far: Preclinical studies suggest that molnupiravir is effective against a number of viruses, including coronaviruses and specifically SARS-CoV-2. It prevents a virus from replicating by inducing viral error catastrophe (Proc Natl Acad Sci U S A. 2002 Oct 15;99[21]:13374-6) – essentially overloading the virus with replication and mutation until the virus burns itself out and can’t produce replicable copies.

In this phase 2a, randomized, double-blind, controlled trial, researchers recruited 202 adults who were treated at an outpatient clinic with fever or other symptoms of a respiratory virus and confirmed SARS-CoV-2 infection by day 4. Participants were randomly assigned to three different groups: 200 mg of molnupiravir, 400 mg, or 800 mg. The 200-mg arm was matched 1:1 with a placebo-controlled group, and the other two groups had three participants in the active group for every one control.

Participants took the pills twice daily for 5 days, and then were followed for a total of 28 days to monitor for complications or adverse events. At days 3, 5, 7, 14, and 28, researchers also took nasopharyngeal swabs for polymerase chain reaction tests, to sequence the virus, and to grow cultures of SARS-CoV-2 to see if the virus that’s present is actually capable of infecting others.

Notably, the pills do not have to be refrigerated at any point in the process, alleviating the cold-chain challenges that have plagued vaccines.

“There’s an urgent need for an easily produced, transported, stored, and administered antiviral drug against SARS-CoV-2,” Dr. Painter said.

Of the 202 people recruited, 182 had swabs that could be evaluated, of which 78 showed infection at baseline. The results are based on labs of those 78 participants.

By day 3, 28% of patients in the placebo arm had SARS-CoV-2 in their nasopharynx, compared with 20.4% of patients receiving any dose of molnupiravir. But by day 5, none of the participants receiving the active drug had evidence of SARS-CoV-2 in their nasopharynx. In comparison, 24% of people in the placebo arm still had detectable virus.

Halfway through the treatment course, differences in the presence of infectious virus were already evident. By day 3 of the 5-day course, 36.4% of participants in the 200-mg group had detectable virus in the nasopharynx, compared with 21% in the 400-mg group and just 12.5% in the 800-mg group. And although the reduction in SARS-CoV-2 was noticeable in the 200-mg and the 400-mg arms, it was only statistically significant in the 800-mg arm.

In contrast, by the end of the 5 days in the placebo groups, infectious virus varied from 18.2% in the 200-mg placebo group to 30% in the 800-mg group. This points out the variability of the disease course of SARS-CoV-2.

“You just don’t know” which infections will lead to serious disease, Dr. Painter said in an interview. “And don’t you wish we did?”

Seven participants discontinued treatment, though only four experienced adverse events. Three of those discontinued the trial because of adverse events. The study is still blinded, so it’s unclear what those events were, but Dr. Painter said that they were not thought to be related to the study drug.

The bottom line, said Dr. Painter, was that people treated with molnupiravir had starkly different outcomes in lab measures during the study.

“An average of 10 days after symptom onset, 24% of placebo patients remained culture positive” for SARS-CoV-2 – meaning there wasn’t just virus in the nasopharynx, but it was capable of replicating, Dr. Painter said. “In contrast, no infectious virus could be recovered at study day 5 in any molnupiravir-treated patients.”

A version of this article first appeared on Medscape.com.

A single pill of the investigational drug molnupiravir taken twice a day for 5 days eliminated SARS-CoV-2 from the nasopharynx of 49 participants.

That led Carlos del Rio, MD, distinguished professor of medicine at Emory University, Atlanta, to suggest a future in which a drug like molnupiravir could be taken in the first few days of symptoms to prevent severe disease, similar to Tamiflu for influenza.

“I think it’s critically important,” he said of the data. Emory University was involved in the trial of molnupiravir but Dr. del Rio was not part of that team. “This drug offers the first antiviral oral drug that then could be used in an outpatient setting.”

Still, Dr. del Rio said it’s too soon to call this particular drug the breakthrough clinicians need to keep people out of the ICU. “It has the potential to be practice changing; it’s not practice changing at the moment.”

Wendy Painter, MD, of Ridgeback Biotherapeutics, who presented the data at the Conference on Retroviruses and Opportunistic Infections, agreed. While the data are promising, “We will need to see if people get better from actual illness” to assess the real value of the drug in clinical care.

“That’s a phase 3 objective we’ll need to prove,” she said in an interview.

Phase 2/3 efficacy and safety studies of the drug are now underway in hospitalized and nonhospitalized patients.

In a brief prerecorded presentation of the data, Dr. Painter laid out what researchers know so far: Preclinical studies suggest that molnupiravir is effective against a number of viruses, including coronaviruses and specifically SARS-CoV-2. It prevents a virus from replicating by inducing viral error catastrophe (Proc Natl Acad Sci U S A. 2002 Oct 15;99[21]:13374-6) – essentially overloading the virus with replication and mutation until the virus burns itself out and can’t produce replicable copies.

In this phase 2a, randomized, double-blind, controlled trial, researchers recruited 202 adults who were treated at an outpatient clinic with fever or other symptoms of a respiratory virus and confirmed SARS-CoV-2 infection by day 4. Participants were randomly assigned to three different groups: 200 mg of molnupiravir, 400 mg, or 800 mg. The 200-mg arm was matched 1:1 with a placebo-controlled group, and the other two groups had three participants in the active group for every one control.

Participants took the pills twice daily for 5 days, and then were followed for a total of 28 days to monitor for complications or adverse events. At days 3, 5, 7, 14, and 28, researchers also took nasopharyngeal swabs for polymerase chain reaction tests, to sequence the virus, and to grow cultures of SARS-CoV-2 to see if the virus that’s present is actually capable of infecting others.

Notably, the pills do not have to be refrigerated at any point in the process, alleviating the cold-chain challenges that have plagued vaccines.

“There’s an urgent need for an easily produced, transported, stored, and administered antiviral drug against SARS-CoV-2,” Dr. Painter said.

Of the 202 people recruited, 182 had swabs that could be evaluated, of which 78 showed infection at baseline. The results are based on labs of those 78 participants.

By day 3, 28% of patients in the placebo arm had SARS-CoV-2 in their nasopharynx, compared with 20.4% of patients receiving any dose of molnupiravir. But by day 5, none of the participants receiving the active drug had evidence of SARS-CoV-2 in their nasopharynx. In comparison, 24% of people in the placebo arm still had detectable virus.

Halfway through the treatment course, differences in the presence of infectious virus were already evident. By day 3 of the 5-day course, 36.4% of participants in the 200-mg group had detectable virus in the nasopharynx, compared with 21% in the 400-mg group and just 12.5% in the 800-mg group. And although the reduction in SARS-CoV-2 was noticeable in the 200-mg and the 400-mg arms, it was only statistically significant in the 800-mg arm.

In contrast, by the end of the 5 days in the placebo groups, infectious virus varied from 18.2% in the 200-mg placebo group to 30% in the 800-mg group. This points out the variability of the disease course of SARS-CoV-2.

“You just don’t know” which infections will lead to serious disease, Dr. Painter said in an interview. “And don’t you wish we did?”

Seven participants discontinued treatment, though only four experienced adverse events. Three of those discontinued the trial because of adverse events. The study is still blinded, so it’s unclear what those events were, but Dr. Painter said that they were not thought to be related to the study drug.

The bottom line, said Dr. Painter, was that people treated with molnupiravir had starkly different outcomes in lab measures during the study.

“An average of 10 days after symptom onset, 24% of placebo patients remained culture positive” for SARS-CoV-2 – meaning there wasn’t just virus in the nasopharynx, but it was capable of replicating, Dr. Painter said. “In contrast, no infectious virus could be recovered at study day 5 in any molnupiravir-treated patients.”

A version of this article first appeared on Medscape.com.