MDedge Infectious Disease

The US Food and Drug Administration (FDA) Nov. 19 issued an emergency use authorization (EUA) for the Janus kinase inhibitor baricitinib (Olumiant, Eli Lilly) in combination with remdesivir (Veklury, Gilead) for treating hospitalized adults and children at least 2 years old with suspected or confirmed COVID-19.

The combination treatment is meant for patients who need supplemental oxygen, mechanical ventilation, or extracorporeal membrane oxygenation (ECMO).

Baricitinib/remdesivir was shown in a clinical trial to reduce time to recovery within 29 days of starting the treatment compared with a control group who received placebo/remdesivir, according to the FDA press release.

The median time to recovery from COVID-19 was 7 days for the combination group vs. 8 days for those in the placebo/remdesivir group. Recovery was defined as either discharge from the hospital or “being hospitalized but not requiring supplemental oxygen and no longer requiring ongoing medical care,” the agency explained in the press release.

The odds of a patient dying or being ventilated at day 29 was lower in the combination group compared with those taking placebo/remdesivir, the press release said without providing specific data. “For all of these endpoints, the effects were statistically significant,” the agency stated.

The safety and efficacy continues to be evaluated. Baricitinib alone is not approved as a treatment for COVID-19.

“The FDA’s emergency authorization of this combination therapy represents an incremental step forward in the treatment of COVID-19 in hospitalized patients, and FDA’s first authorization of a drug that acts on the inflammation pathway,” said Patrizia Cavazzoni, MD, acting director of the FDA’s Center for Drug Evaluation and Research.

“Despite advances in the management of COVID-19 infection since the onset of the pandemic, we need more therapies to accelerate recovery and additional clinical research will be essential to identifying therapies that slow disease progression and lower mortality in the sicker patients,” she said.

As a JAK inhibitor, baricitinib interferes with a pathway that leads to inflammation. Baricitinib is already prescribed as an oral medication and is FDA-approved for treating moderate to severe rheumatoid arthritis.

The data supporting the EUA for the combination treatment are based on a randomized, double-blind, placebo-controlled clinical trial (ACTT-2), conducted by the National Institute of Allergy and Infectious Diseases (NIAID).

The trial followed patients for 29 days and included 1,033 patients with moderate to severe COVID-19; 515 patients received baricitinib/remdesivir, and 518 patients received placebo/remdesivir.

The FDA emphasizes that an EUA is not a full FDA approval.

In reviewing the combination, the FDA “determined that it is reasonable to believe that baricitinib, in combination with remdesivir, may be effective in treating COVID-19 for the authorized population” and the known benefits outweigh the known and potential risks. Additionally, there are no adequate, approved, and available alternatives for the treatment population.

“Today’s action demonstrates the FDA’s steadfast efforts to make potential COVID-19 treatments available in a timely manner, where appropriate, while continuing to support research to further evaluate whether they are safe and effective,” said FDA Commissioner Stephen M. Hahn, MD. “As part of our Coronavirus Treatment Acceleration Program, the FDA continues to use every possible avenue to facilitate new treatments for patients as quickly as possible to combat COVID-19.”
 

This article first appeared on Medscape.com.

The US Food and Drug Administration (FDA) Nov. 19 issued an emergency use authorization (EUA) for the Janus kinase inhibitor baricitinib (Olumiant, Eli Lilly) in combination with remdesivir (Veklury, Gilead) for treating hospitalized adults and children at least 2 years old with suspected or confirmed COVID-19.

The combination treatment is meant for patients who need supplemental oxygen, mechanical ventilation, or extracorporeal membrane oxygenation (ECMO).

Baricitinib/remdesivir was shown in a clinical trial to reduce time to recovery within 29 days of starting the treatment compared with a control group who received placebo/remdesivir, according to the FDA press release.

The median time to recovery from COVID-19 was 7 days for the combination group vs. 8 days for those in the placebo/remdesivir group. Recovery was defined as either discharge from the hospital or “being hospitalized but not requiring supplemental oxygen and no longer requiring ongoing medical care,” the agency explained in the press release.

The odds of a patient dying or being ventilated at day 29 was lower in the combination group compared with those taking placebo/remdesivir, the press release said without providing specific data. “For all of these endpoints, the effects were statistically significant,” the agency stated.

The safety and efficacy continues to be evaluated. Baricitinib alone is not approved as a treatment for COVID-19.

“The FDA’s emergency authorization of this combination therapy represents an incremental step forward in the treatment of COVID-19 in hospitalized patients, and FDA’s first authorization of a drug that acts on the inflammation pathway,” said Patrizia Cavazzoni, MD, acting director of the FDA’s Center for Drug Evaluation and Research.

“Despite advances in the management of COVID-19 infection since the onset of the pandemic, we need more therapies to accelerate recovery and additional clinical research will be essential to identifying therapies that slow disease progression and lower mortality in the sicker patients,” she said.

As a JAK inhibitor, baricitinib interferes with a pathway that leads to inflammation. Baricitinib is already prescribed as an oral medication and is FDA-approved for treating moderate to severe rheumatoid arthritis.

The data supporting the EUA for the combination treatment are based on a randomized, double-blind, placebo-controlled clinical trial (ACTT-2), conducted by the National Institute of Allergy and Infectious Diseases (NIAID).

The trial followed patients for 29 days and included 1,033 patients with moderate to severe COVID-19; 515 patients received baricitinib/remdesivir, and 518 patients received placebo/remdesivir.

The FDA emphasizes that an EUA is not a full FDA approval.

In reviewing the combination, the FDA “determined that it is reasonable to believe that baricitinib, in combination with remdesivir, may be effective in treating COVID-19 for the authorized population” and the known benefits outweigh the known and potential risks. Additionally, there are no adequate, approved, and available alternatives for the treatment population.

“Today’s action demonstrates the FDA’s steadfast efforts to make potential COVID-19 treatments available in a timely manner, where appropriate, while continuing to support research to further evaluate whether they are safe and effective,” said FDA Commissioner Stephen M. Hahn, MD. “As part of our Coronavirus Treatment Acceleration Program, the FDA continues to use every possible avenue to facilitate new treatments for patients as quickly as possible to combat COVID-19.”
 

This article first appeared on Medscape.com.

The US Food and Drug Administration (FDA) Nov. 19 issued an emergency use authorization (EUA) for the Janus kinase inhibitor baricitinib (Olumiant, Eli Lilly) in combination with remdesivir (Veklury, Gilead) for treating hospitalized adults and children at least 2 years old with suspected or confirmed COVID-19.

The combination treatment is meant for patients who need supplemental oxygen, mechanical ventilation, or extracorporeal membrane oxygenation (ECMO).

Baricitinib/remdesivir was shown in a clinical trial to reduce time to recovery within 29 days of starting the treatment compared with a control group who received placebo/remdesivir, according to the FDA press release.

The median time to recovery from COVID-19 was 7 days for the combination group vs. 8 days for those in the placebo/remdesivir group. Recovery was defined as either discharge from the hospital or “being hospitalized but not requiring supplemental oxygen and no longer requiring ongoing medical care,” the agency explained in the press release.

The odds of a patient dying or being ventilated at day 29 was lower in the combination group compared with those taking placebo/remdesivir, the press release said without providing specific data. “For all of these endpoints, the effects were statistically significant,” the agency stated.

The safety and efficacy continues to be evaluated. Baricitinib alone is not approved as a treatment for COVID-19.

“The FDA’s emergency authorization of this combination therapy represents an incremental step forward in the treatment of COVID-19 in hospitalized patients, and FDA’s first authorization of a drug that acts on the inflammation pathway,” said Patrizia Cavazzoni, MD, acting director of the FDA’s Center for Drug Evaluation and Research.

“Despite advances in the management of COVID-19 infection since the onset of the pandemic, we need more therapies to accelerate recovery and additional clinical research will be essential to identifying therapies that slow disease progression and lower mortality in the sicker patients,” she said.

As a JAK inhibitor, baricitinib interferes with a pathway that leads to inflammation. Baricitinib is already prescribed as an oral medication and is FDA-approved for treating moderate to severe rheumatoid arthritis.

The data supporting the EUA for the combination treatment are based on a randomized, double-blind, placebo-controlled clinical trial (ACTT-2), conducted by the National Institute of Allergy and Infectious Diseases (NIAID).

The trial followed patients for 29 days and included 1,033 patients with moderate to severe COVID-19; 515 patients received baricitinib/remdesivir, and 518 patients received placebo/remdesivir.

The FDA emphasizes that an EUA is not a full FDA approval.

In reviewing the combination, the FDA “determined that it is reasonable to believe that baricitinib, in combination with remdesivir, may be effective in treating COVID-19 for the authorized population” and the known benefits outweigh the known and potential risks. Additionally, there are no adequate, approved, and available alternatives for the treatment population.

“Today’s action demonstrates the FDA’s steadfast efforts to make potential COVID-19 treatments available in a timely manner, where appropriate, while continuing to support research to further evaluate whether they are safe and effective,” said FDA Commissioner Stephen M. Hahn, MD. “As part of our Coronavirus Treatment Acceleration Program, the FDA continues to use every possible avenue to facilitate new treatments for patients as quickly as possible to combat COVID-19.”
 

This article first appeared on Medscape.com.

Loss of the hepatitis B surface antigen (HBsAg), a marker for functional cure of hepatitis B infection, is nearly six times more common among White patients than Asian patients following cessation of therapy with a nucleotide or nucleoside analogue, investigators in the RETRACT-B study group report.

Among 1,541 patients in a global retrospective cohort, the cumulative rate of HBsAg loss 4 years after cessation of therapy with entecavir (ETV), tenofovir disoproxil fumarate (TDF), or other nucleoside/nucleotide analogue (“nuc” or NA) was 11% in Asian patients, compared with 41% in Whites, which translated in multivariate analysis into a hazard ratio (HR) of 5.8 (P < .001), said Grishma Hirode, a clinical research associate and PhD candidate at the Toronto Centre for Liver Disease.

“On univariate Cox regression, the rate of S [antigen] loss was significantly higher among older patients, among [Whites], and among tenofovir-treated patients prior to stopping,” she said during the virtual annual meeting of the American Association for the Study of Liver Diseases.

Although NAs are effective at suppressing hepatitis B viral activity, functional cure as indicated by HBsAg loss is uncommon, Ms. Hirode noted.

“Finite use of antiviral therapy has been proposed as an alternative to long-term therapy, and the rationale for stopping nuc therapy is to induce a durable virologic remission in the form of an inactive carrier state, and ideally a functional cure,” she said.

The RETRACT-B (Response after End of Treatment with Antivirals in Chronic Hepatitis B) study group, comprising liver treatment centers in Canada, Europe, Hong Kong, and Taiwan, studies outcomes following cessation of nucleos(t)ide analogue therapy.

The investigators looked at data on 1,541 patients, including those with both hepatitis B e-antigen (HBeAg) positive and HBeAg-negative disease at the start of therapy, all of whom were HBeAg negative at the time of antiviral cessation and had undetectable serum HBV DNA. Patients with hepatitis C, hepatitis D and/or HIV co-infection were excluded, as were patients who had received interferon treatment less than 12 months before stopping.

The mean age at baseline was 53 years. Men comprised 73% of the sample. In all, 88% of patients were Asian, 10% White, and 2% other.

In patients for whom genotype data was known, 0.5% had type A, 43% type B, 11% type C, and 2% type D.

Nearly two-thirds of patients (60%) were on ETV at the time of drug cessation, 29% were on TDF, and 11% were on other agents.

In all, 5% of patients had cirrhosis at the time of nucleos(t)ide cessation, the mean HBsAg was 2.6 log₁₀ IU/mL, and the mean alanine aminotransferase (ALT) level was 0.6 times the upper limit of normal.

The median duration of NA therapy was 3 years.

The cumulative rates of HBsAg loss over time among all patients was 3% at 1 year, 8% at 2 years. 12% at 3 years, and 14% at 4 years. Cumulative rates of antigen loss at year 4 were significantly greater for patients 50 and older vs. those younger than 50 (18% vs. 9%, respectively, P = .01), Whites vs. Asians (41% vs. 11%, P < .001), and in those who had been on TDF vs. ETV (17% vs. 12%, P = .001). There was no significant difference in cumulative HBsAg loss between patients who were HBeAg positive or negative at the start of NA therapy.

Cumulative rates of retreatment were 30% at 1 year, 43% at 2 years, 50% at 3 years, and 56% at 4 years. The only significant predictor for retreatment was age, with patients 50 and older being significantly more likely to be retreated by year 4 (63% vs. 45%, respectively, P < .001).

In a univariate model for HBsAg loss, the HR for age 50 and older was 1.7 (P = .01), the HR for White vs. Asian patients was 5.5 (P < .001), and the HR for TDF vs. ETV was 2.0 (P = .001).

A univariate model for retreatment showed an HR of 1.6 for patients 50 and older; all other parameters (sex, race, NA type, and HBeAg status at start of therapy) were not significantly different.

In multivariate models, only race/ethnicity remained significant as a predictor for HBsAg loss, with a HR of 5.8 for Whites vs. Asians (P < .001), and only age 50 and older remained significant as a predictor for retreatment, with a HR of 1.6 (P < .001).

The 4-year cumulative rate of virologic relapse, defined as an HBV DNA of 2000 IU/mL or higher) was 74%, the rate of combined DNA plus ALT relapse (ALT 2 or more times the upper limit of normal) was 56%, and the rate of ALT flares (5 or more times the upper limit of normal) was 33%.

In all, 15 patients (1%) experienced hepatic decompensation, and 12 (0.96%) died, with 9 of the deaths reported as liver-related.
 

Race/ethnicity differences previously seen

Liver specialist Anna Suk-Fong Lok, MD, professor of medicine at the University of Michigan in Ann Arbor, who was not involved in the study, said that the findings are not especially surprising.

“When the studies came out from Asian countries showing that patients who were taken off treatment had a higher rate of S antigen loss than patients who stayed on treatment, the rate of S antigen loss was not all that impressive, but when you look at the European studies the rate of S antigen loss was very high,” she said in an interview.

“The question of course is ‘Why?’ I don’t think we understand completely why. We can speculate, but none of these type studies give us a definitive answer,” she said.

Possible reasons for the racial differences in HBsAg loss include differences in hepatitis B genotype, she said.

“Another possibility is that Asian patients may have been infected either at the time of birth or as a young kid, so they may have been infected for a much longer period of time than [Whites], who usually acquire infections as adults,” Dr. Lok said.

There may also be differences between patient populations in immune responses following cessation of antiviral therapy, she added.

The study was supported by the RETRACT-B group. Ms. Hirode and Dr. Lok reported no relevant disclosures.

SOURCE: Hirode G et al. AASLD 2020. Abstract 23.

Loss of the hepatitis B surface antigen (HBsAg), a marker for functional cure of hepatitis B infection, is nearly six times more common among White patients than Asian patients following cessation of therapy with a nucleotide or nucleoside analogue, investigators in the RETRACT-B study group report.

Among 1,541 patients in a global retrospective cohort, the cumulative rate of HBsAg loss 4 years after cessation of therapy with entecavir (ETV), tenofovir disoproxil fumarate (TDF), or other nucleoside/nucleotide analogue (“nuc” or NA) was 11% in Asian patients, compared with 41% in Whites, which translated in multivariate analysis into a hazard ratio (HR) of 5.8 (P < .001), said Grishma Hirode, a clinical research associate and PhD candidate at the Toronto Centre for Liver Disease.

“On univariate Cox regression, the rate of S [antigen] loss was significantly higher among older patients, among [Whites], and among tenofovir-treated patients prior to stopping,” she said during the virtual annual meeting of the American Association for the Study of Liver Diseases.

Although NAs are effective at suppressing hepatitis B viral activity, functional cure as indicated by HBsAg loss is uncommon, Ms. Hirode noted.

“Finite use of antiviral therapy has been proposed as an alternative to long-term therapy, and the rationale for stopping nuc therapy is to induce a durable virologic remission in the form of an inactive carrier state, and ideally a functional cure,” she said.

The RETRACT-B (Response after End of Treatment with Antivirals in Chronic Hepatitis B) study group, comprising liver treatment centers in Canada, Europe, Hong Kong, and Taiwan, studies outcomes following cessation of nucleos(t)ide analogue therapy.

The investigators looked at data on 1,541 patients, including those with both hepatitis B e-antigen (HBeAg) positive and HBeAg-negative disease at the start of therapy, all of whom were HBeAg negative at the time of antiviral cessation and had undetectable serum HBV DNA. Patients with hepatitis C, hepatitis D and/or HIV co-infection were excluded, as were patients who had received interferon treatment less than 12 months before stopping.

The mean age at baseline was 53 years. Men comprised 73% of the sample. In all, 88% of patients were Asian, 10% White, and 2% other.

In patients for whom genotype data was known, 0.5% had type A, 43% type B, 11% type C, and 2% type D.

Nearly two-thirds of patients (60%) were on ETV at the time of drug cessation, 29% were on TDF, and 11% were on other agents.

In all, 5% of patients had cirrhosis at the time of nucleos(t)ide cessation, the mean HBsAg was 2.6 log₁₀ IU/mL, and the mean alanine aminotransferase (ALT) level was 0.6 times the upper limit of normal.

The median duration of NA therapy was 3 years.

The cumulative rates of HBsAg loss over time among all patients was 3% at 1 year, 8% at 2 years. 12% at 3 years, and 14% at 4 years. Cumulative rates of antigen loss at year 4 were significantly greater for patients 50 and older vs. those younger than 50 (18% vs. 9%, respectively, P = .01), Whites vs. Asians (41% vs. 11%, P < .001), and in those who had been on TDF vs. ETV (17% vs. 12%, P = .001). There was no significant difference in cumulative HBsAg loss between patients who were HBeAg positive or negative at the start of NA therapy.

Cumulative rates of retreatment were 30% at 1 year, 43% at 2 years, 50% at 3 years, and 56% at 4 years. The only significant predictor for retreatment was age, with patients 50 and older being significantly more likely to be retreated by year 4 (63% vs. 45%, respectively, P < .001).

In a univariate model for HBsAg loss, the HR for age 50 and older was 1.7 (P = .01), the HR for White vs. Asian patients was 5.5 (P < .001), and the HR for TDF vs. ETV was 2.0 (P = .001).

A univariate model for retreatment showed an HR of 1.6 for patients 50 and older; all other parameters (sex, race, NA type, and HBeAg status at start of therapy) were not significantly different.

In multivariate models, only race/ethnicity remained significant as a predictor for HBsAg loss, with a HR of 5.8 for Whites vs. Asians (P < .001), and only age 50 and older remained significant as a predictor for retreatment, with a HR of 1.6 (P < .001).

The 4-year cumulative rate of virologic relapse, defined as an HBV DNA of 2000 IU/mL or higher) was 74%, the rate of combined DNA plus ALT relapse (ALT 2 or more times the upper limit of normal) was 56%, and the rate of ALT flares (5 or more times the upper limit of normal) was 33%.

In all, 15 patients (1%) experienced hepatic decompensation, and 12 (0.96%) died, with 9 of the deaths reported as liver-related.
 

Race/ethnicity differences previously seen

Liver specialist Anna Suk-Fong Lok, MD, professor of medicine at the University of Michigan in Ann Arbor, who was not involved in the study, said that the findings are not especially surprising.

“When the studies came out from Asian countries showing that patients who were taken off treatment had a higher rate of S antigen loss than patients who stayed on treatment, the rate of S antigen loss was not all that impressive, but when you look at the European studies the rate of S antigen loss was very high,” she said in an interview.

“The question of course is ‘Why?’ I don’t think we understand completely why. We can speculate, but none of these type studies give us a definitive answer,” she said.

Possible reasons for the racial differences in HBsAg loss include differences in hepatitis B genotype, she said.

“Another possibility is that Asian patients may have been infected either at the time of birth or as a young kid, so they may have been infected for a much longer period of time than [Whites], who usually acquire infections as adults,” Dr. Lok said.

There may also be differences between patient populations in immune responses following cessation of antiviral therapy, she added.

The study was supported by the RETRACT-B group. Ms. Hirode and Dr. Lok reported no relevant disclosures.

SOURCE: Hirode G et al. AASLD 2020. Abstract 23.

Loss of the hepatitis B surface antigen (HBsAg), a marker for functional cure of hepatitis B infection, is nearly six times more common among White patients than Asian patients following cessation of therapy with a nucleotide or nucleoside analogue, investigators in the RETRACT-B study group report.

Among 1,541 patients in a global retrospective cohort, the cumulative rate of HBsAg loss 4 years after cessation of therapy with entecavir (ETV), tenofovir disoproxil fumarate (TDF), or other nucleoside/nucleotide analogue (“nuc” or NA) was 11% in Asian patients, compared with 41% in Whites, which translated in multivariate analysis into a hazard ratio (HR) of 5.8 (P < .001), said Grishma Hirode, a clinical research associate and PhD candidate at the Toronto Centre for Liver Disease.

“On univariate Cox regression, the rate of S [antigen] loss was significantly higher among older patients, among [Whites], and among tenofovir-treated patients prior to stopping,” she said during the virtual annual meeting of the American Association for the Study of Liver Diseases.

Although NAs are effective at suppressing hepatitis B viral activity, functional cure as indicated by HBsAg loss is uncommon, Ms. Hirode noted.

“Finite use of antiviral therapy has been proposed as an alternative to long-term therapy, and the rationale for stopping nuc therapy is to induce a durable virologic remission in the form of an inactive carrier state, and ideally a functional cure,” she said.

The RETRACT-B (Response after End of Treatment with Antivirals in Chronic Hepatitis B) study group, comprising liver treatment centers in Canada, Europe, Hong Kong, and Taiwan, studies outcomes following cessation of nucleos(t)ide analogue therapy.

The investigators looked at data on 1,541 patients, including those with both hepatitis B e-antigen (HBeAg) positive and HBeAg-negative disease at the start of therapy, all of whom were HBeAg negative at the time of antiviral cessation and had undetectable serum HBV DNA. Patients with hepatitis C, hepatitis D and/or HIV co-infection were excluded, as were patients who had received interferon treatment less than 12 months before stopping.

The mean age at baseline was 53 years. Men comprised 73% of the sample. In all, 88% of patients were Asian, 10% White, and 2% other.

In patients for whom genotype data was known, 0.5% had type A, 43% type B, 11% type C, and 2% type D.

Nearly two-thirds of patients (60%) were on ETV at the time of drug cessation, 29% were on TDF, and 11% were on other agents.

In all, 5% of patients had cirrhosis at the time of nucleos(t)ide cessation, the mean HBsAg was 2.6 log₁₀ IU/mL, and the mean alanine aminotransferase (ALT) level was 0.6 times the upper limit of normal.

The median duration of NA therapy was 3 years.

The cumulative rates of HBsAg loss over time among all patients was 3% at 1 year, 8% at 2 years. 12% at 3 years, and 14% at 4 years. Cumulative rates of antigen loss at year 4 were significantly greater for patients 50 and older vs. those younger than 50 (18% vs. 9%, respectively, P = .01), Whites vs. Asians (41% vs. 11%, P < .001), and in those who had been on TDF vs. ETV (17% vs. 12%, P = .001). There was no significant difference in cumulative HBsAg loss between patients who were HBeAg positive or negative at the start of NA therapy.

Cumulative rates of retreatment were 30% at 1 year, 43% at 2 years, 50% at 3 years, and 56% at 4 years. The only significant predictor for retreatment was age, with patients 50 and older being significantly more likely to be retreated by year 4 (63% vs. 45%, respectively, P < .001).

In a univariate model for HBsAg loss, the HR for age 50 and older was 1.7 (P = .01), the HR for White vs. Asian patients was 5.5 (P < .001), and the HR for TDF vs. ETV was 2.0 (P = .001).

A univariate model for retreatment showed an HR of 1.6 for patients 50 and older; all other parameters (sex, race, NA type, and HBeAg status at start of therapy) were not significantly different.

In multivariate models, only race/ethnicity remained significant as a predictor for HBsAg loss, with a HR of 5.8 for Whites vs. Asians (P < .001), and only age 50 and older remained significant as a predictor for retreatment, with a HR of 1.6 (P < .001).

The 4-year cumulative rate of virologic relapse, defined as an HBV DNA of 2000 IU/mL or higher) was 74%, the rate of combined DNA plus ALT relapse (ALT 2 or more times the upper limit of normal) was 56%, and the rate of ALT flares (5 or more times the upper limit of normal) was 33%.

In all, 15 patients (1%) experienced hepatic decompensation, and 12 (0.96%) died, with 9 of the deaths reported as liver-related.
 

Race/ethnicity differences previously seen

Liver specialist Anna Suk-Fong Lok, MD, professor of medicine at the University of Michigan in Ann Arbor, who was not involved in the study, said that the findings are not especially surprising.

“When the studies came out from Asian countries showing that patients who were taken off treatment had a higher rate of S antigen loss than patients who stayed on treatment, the rate of S antigen loss was not all that impressive, but when you look at the European studies the rate of S antigen loss was very high,” she said in an interview.

“The question of course is ‘Why?’ I don’t think we understand completely why. We can speculate, but none of these type studies give us a definitive answer,” she said.

Possible reasons for the racial differences in HBsAg loss include differences in hepatitis B genotype, she said.

“Another possibility is that Asian patients may have been infected either at the time of birth or as a young kid, so they may have been infected for a much longer period of time than [Whites], who usually acquire infections as adults,” Dr. Lok said.

There may also be differences between patient populations in immune responses following cessation of antiviral therapy, she added.

The study was supported by the RETRACT-B group. Ms. Hirode and Dr. Lok reported no relevant disclosures.

SOURCE: Hirode G et al. AASLD 2020. Abstract 23.

One of the most remarkable stories in medicine must be the relatively brief 25 years between the discovery of the hepatitis C virus (HCV) in 1989 to its eventual cure in 2014.

HCV afflicted over 5 million Americans and was the cause of death in approximately 10,000 patients annually, the leading indication for liver transplantation, and the leading risk factor for hepatocellular carcinoma, clearly signaling it as one of the era’s major public health villains. Within that span of time, it is the work beginning in the mid-1990s until today that perhaps best defines the race for the HCV “cure.”

In the early to mid-1990s, polymerase chain reaction techniques were just becoming commonplace for HCV diagnosis, whereas HCV genotypes were emerging as major factors determining response to interferon therapy. The sustained viral response (SVR) rates were mired at around 6%-12% for a 24- to 48-week course of three-times-weekly injection therapy. Severe side effects were common and there was a relatively high relapse rate, even in patients who responded to treatment.

By 1996, the addition of ribavirin to the interferon treatment was associated with a modest but significant improvement in SVR rates to above 20%. And by 2000, the use of pegylated interferon – allowing once-weekly injection therapy – along with ribavirin, improved SVR rates to above 50% for the first time. The therapy was still poorly tolerated but was associated with better compliance.

The real breakthrough in therapy came in the early 2000s with the discovery and availability of HCV protease inhibitors: telaprevir and boceprevir. These agents could induce a more rapid decline in viral replication than interferon but could not be administered alone owing to the rapid emergence of resistant HCV variants. Therefore, these agents were administered with interferon and ribavirin as a three-drug cocktail to take advantage of interferon to prevent emergence of resistant variants. Although SVR rates improved substantially to around 75%, adverse events also increased and limited its usefulness in patients with more advanced liver disease, precisely those who were most in need of better therapies.

Nonetheless, the incredible advances in understanding the replication machinery of HCV that led to the discovery of the protease inhibitors in turn led to further elucidation and unlocking of three additional classes of HCV protein targets and inhibitors: NS5A complex inhibitors (e.g., ledipasvir), the NS5B nonnucleoside inhibitors (e.g., dasabuvir), and NS5B nucleoside inhibitors (e.g., sofosbuvir). It quickly became apparent that the use of combinations of these direct-acting antivirals (DAAs) could limit emergence of resistant variants while also providing rapid and profound viral suppression. Because HCV required viral replication to persist in the hepatocyte, it became possible to induce HCV eradication, and thus cure, with combinations of DAAs.

In addition, investigators soon learned that the duration of therapy no longer needed to be the generally accepted 24-48 weeks for SVR, but instead could be reduced eventually to 8-12 weeks. This shortened treatment duration allowed for more rapid testing of new agents and combinations, and the field took a rapid step forward between 2011 and 2017. HCV cure rates rose to 90%-95%.

The competition for Food and Drug Administration approval of new agents among several pharmaceutical companies also meant that the time-honored process of issuing treatment guidelines every 3-5 years by societies would not be adequate. Therefore, in 2013, the American Association for the Study of Liver Diseases and the Infectious Diseases Society of America joined forces to establish more nimble and responsive online HCV guidance. This important resource debuted in January 2014 just as the FDA approved the first DAA therapies.

The high cost initially associated with many of these new therapies (up to $1,000 per pill) significantly limited uptake owing to insurance and health plan cost factors. Early on, the cost was also analyzed by price per cure, seemingly to justify the high cost by the high cure rate. However, advocacy and negotiations ultimately led to marked reductions in the cost of a course of therapy (with some therapies at $225 per pill), thus making these treatments now widely available.

By 2020, the HCV field has shifted from therapeutic development to improving the care cascade by enhanced identification and testing of unsuspected but HCV infected individuals. This is our current challenge.
 

Moving toward noninvasive tests

While curative therapy has revolutionized HCV management, innovation in diagnostics eliminated a significant barrier in access to therapy: the liver biopsy.

Staging, or accurately identifying advanced fibrosis in persons infected with HCV, is essential for long-term follow-up. The presence of advanced disease affects drug choices, especially before the approval of all-oral therapy. Historically, a liver biopsy was obligatory before treatment. Invasive with a significant risk for complications, this requirement effectively prevented treatment in those who were unwilling to undergo the procedure and deterred those at risk from even being tested.

Over the past 25 years, numerous methods to noninvasively assess for liver fibrosis have been used. Serum biomarkers can be either indirect (based on routine tests) or direct (reflecting components of the extracellular matrix). Although highly available, they are only moderately useful for identifying advanced fibrosis and thus cannot replace liver biopsy in the care cascade. The technique of elastography dates back to the 1980s, though the role of vibration-controlled transient liver elastography in the assessment of hepatic fibrosis in patients with HCV was not recognized until around 2005 and it was not commonly used for nearly another decade.

Yet, a paradigm shift in the care cascade occurred with the release of the AASLD/IDSA guidance document in 2014. For the first time in the United States, noninvasive tests were recommended as first-line testing for the assessment of advanced fibrosis. Prior guidelines specifically stated that although noninvasive tests might be useful, they “should not replace the liver biopsy in routine clinical practice.” Current guidelines recommend combining elastography with serum biomarkers and considering biopsy only in patients with discordant results if the biopsy would affect clinical decision-making.
 

The last frontier

Curative therapy has also allowed the unthinkable: willingly exposing patients to the virus through donor-positive/recipient-negative solid organ transplant. Traditionally, an HCV-infected donor would be considered only for an HCV-positive recipient; however, with effective DAA therapy, the number of HCV actively infected patients in need of transplant has dwindled.

Unfortunately as a consequence of the opioid epidemic, the HCV-exposed donor population has blossomed. Given that HCV therapy is near universally curative, using organs from HCV-viremic donors can greatly expand the organ transplantation pool. Small studies[1-5] have demonstrated the safety and efficacy of this approach, both in HCV-positive liver donors as well as in other solid organs.
 

A disease pegged for elimination

In the past 25 years, HCV has evolved from non-A, non-B hepatitis into a disease pegged for elimination. This is a direct reflection of improved therapeutics with highly effective DAAs. Yet, without improved diagnostics, we would be unable to navigate patients through the clinical care cascade. These incredible strides in diagnostics and therapeutics allow us to push the cutting edge through iatrogenic infection of organ recipients, while recognizing that the largest hurdle to elimination remains in finding those who are chronically infected. Ultimately, the crux of elimination remains unchanged over the past 25 years and resides in screening and diagnosis with effective linkage to care.

Donald M. Jensen, MD, is a professor of medicine at Rush University Medical Center, Chicago. He was previously the director of the Center for Liver Disease at the University of Chicago until 2015. His research interest has been in newer HCV therapies. He recently received the Distinguished Service Award from the AASLD for his many contributions to the field.

Nancy S. Reau, MD, is chief of the hepatology section at Rush University Medical Center and a regular contributor to Medscape. She serves as editor of Clinical Liver Disease, a multimedia review journal, and recently as a member of HCVGuidelines.org, a web-based resource from the AASLD and the IDSA, as well as educational chair for the AASLD hepatitis C special interest group. She continues to have an active role in the hepatology interest group of the World Gastroenterology Organisation and the American Liver Foundation at the regional and national levels.
 

References

Woolley AE et al. Heart and lung transplants from HCV-infected donors to uninfected recipients. N Engl J Med. 2019;380:1606-17.

Franco A et al. Renal transplantation from seropositive hepatitis C virus donors to seronegative recipients in Spain: A prospective study. Transpl Int. 2019;32:710-6.

Goldberg DS et al. Transplanting HCV-infected kidneys into uninfected recipients. N Engl J Med. 2017;377:1105.

Kwong AJ et al. Liver transplantation for hepatitis C virus (HCV) nonviremic recipients with HCV viremic donors. Am J Transplant. 2019;19:1380-7.

Bethea E et al. Immediate administration of antiviral therapy after transplantation of hepatitis C–infected livers into uninfected recipients: Implications for therapeutic planning. Am J Transplant. 2020;20:1619-28.

This article first appeared on Medscape.com.

One of the most remarkable stories in medicine must be the relatively brief 25 years between the discovery of the hepatitis C virus (HCV) in 1989 to its eventual cure in 2014.

HCV afflicted over 5 million Americans and was the cause of death in approximately 10,000 patients annually, the leading indication for liver transplantation, and the leading risk factor for hepatocellular carcinoma, clearly signaling it as one of the era’s major public health villains. Within that span of time, it is the work beginning in the mid-1990s until today that perhaps best defines the race for the HCV “cure.”

In the early to mid-1990s, polymerase chain reaction techniques were just becoming commonplace for HCV diagnosis, whereas HCV genotypes were emerging as major factors determining response to interferon therapy. The sustained viral response (SVR) rates were mired at around 6%-12% for a 24- to 48-week course of three-times-weekly injection therapy. Severe side effects were common and there was a relatively high relapse rate, even in patients who responded to treatment.

By 1996, the addition of ribavirin to the interferon treatment was associated with a modest but significant improvement in SVR rates to above 20%. And by 2000, the use of pegylated interferon – allowing once-weekly injection therapy – along with ribavirin, improved SVR rates to above 50% for the first time. The therapy was still poorly tolerated but was associated with better compliance.

The real breakthrough in therapy came in the early 2000s with the discovery and availability of HCV protease inhibitors: telaprevir and boceprevir. These agents could induce a more rapid decline in viral replication than interferon but could not be administered alone owing to the rapid emergence of resistant HCV variants. Therefore, these agents were administered with interferon and ribavirin as a three-drug cocktail to take advantage of interferon to prevent emergence of resistant variants. Although SVR rates improved substantially to around 75%, adverse events also increased and limited its usefulness in patients with more advanced liver disease, precisely those who were most in need of better therapies.

Nonetheless, the incredible advances in understanding the replication machinery of HCV that led to the discovery of the protease inhibitors in turn led to further elucidation and unlocking of three additional classes of HCV protein targets and inhibitors: NS5A complex inhibitors (e.g., ledipasvir), the NS5B nonnucleoside inhibitors (e.g., dasabuvir), and NS5B nucleoside inhibitors (e.g., sofosbuvir). It quickly became apparent that the use of combinations of these direct-acting antivirals (DAAs) could limit emergence of resistant variants while also providing rapid and profound viral suppression. Because HCV required viral replication to persist in the hepatocyte, it became possible to induce HCV eradication, and thus cure, with combinations of DAAs.

In addition, investigators soon learned that the duration of therapy no longer needed to be the generally accepted 24-48 weeks for SVR, but instead could be reduced eventually to 8-12 weeks. This shortened treatment duration allowed for more rapid testing of new agents and combinations, and the field took a rapid step forward between 2011 and 2017. HCV cure rates rose to 90%-95%.

The competition for Food and Drug Administration approval of new agents among several pharmaceutical companies also meant that the time-honored process of issuing treatment guidelines every 3-5 years by societies would not be adequate. Therefore, in 2013, the American Association for the Study of Liver Diseases and the Infectious Diseases Society of America joined forces to establish more nimble and responsive online HCV guidance. This important resource debuted in January 2014 just as the FDA approved the first DAA therapies.

The high cost initially associated with many of these new therapies (up to $1,000 per pill) significantly limited uptake owing to insurance and health plan cost factors. Early on, the cost was also analyzed by price per cure, seemingly to justify the high cost by the high cure rate. However, advocacy and negotiations ultimately led to marked reductions in the cost of a course of therapy (with some therapies at $225 per pill), thus making these treatments now widely available.

By 2020, the HCV field has shifted from therapeutic development to improving the care cascade by enhanced identification and testing of unsuspected but HCV infected individuals. This is our current challenge.
 

Moving toward noninvasive tests

While curative therapy has revolutionized HCV management, innovation in diagnostics eliminated a significant barrier in access to therapy: the liver biopsy.

Staging, or accurately identifying advanced fibrosis in persons infected with HCV, is essential for long-term follow-up. The presence of advanced disease affects drug choices, especially before the approval of all-oral therapy. Historically, a liver biopsy was obligatory before treatment. Invasive with a significant risk for complications, this requirement effectively prevented treatment in those who were unwilling to undergo the procedure and deterred those at risk from even being tested.

Over the past 25 years, numerous methods to noninvasively assess for liver fibrosis have been used. Serum biomarkers can be either indirect (based on routine tests) or direct (reflecting components of the extracellular matrix). Although highly available, they are only moderately useful for identifying advanced fibrosis and thus cannot replace liver biopsy in the care cascade. The technique of elastography dates back to the 1980s, though the role of vibration-controlled transient liver elastography in the assessment of hepatic fibrosis in patients with HCV was not recognized until around 2005 and it was not commonly used for nearly another decade.

Yet, a paradigm shift in the care cascade occurred with the release of the AASLD/IDSA guidance document in 2014. For the first time in the United States, noninvasive tests were recommended as first-line testing for the assessment of advanced fibrosis. Prior guidelines specifically stated that although noninvasive tests might be useful, they “should not replace the liver biopsy in routine clinical practice.” Current guidelines recommend combining elastography with serum biomarkers and considering biopsy only in patients with discordant results if the biopsy would affect clinical decision-making.
 

The last frontier

Curative therapy has also allowed the unthinkable: willingly exposing patients to the virus through donor-positive/recipient-negative solid organ transplant. Traditionally, an HCV-infected donor would be considered only for an HCV-positive recipient; however, with effective DAA therapy, the number of HCV actively infected patients in need of transplant has dwindled.

Unfortunately as a consequence of the opioid epidemic, the HCV-exposed donor population has blossomed. Given that HCV therapy is near universally curative, using organs from HCV-viremic donors can greatly expand the organ transplantation pool. Small studies[1-5] have demonstrated the safety and efficacy of this approach, both in HCV-positive liver donors as well as in other solid organs.
 

A disease pegged for elimination

In the past 25 years, HCV has evolved from non-A, non-B hepatitis into a disease pegged for elimination. This is a direct reflection of improved therapeutics with highly effective DAAs. Yet, without improved diagnostics, we would be unable to navigate patients through the clinical care cascade. These incredible strides in diagnostics and therapeutics allow us to push the cutting edge through iatrogenic infection of organ recipients, while recognizing that the largest hurdle to elimination remains in finding those who are chronically infected. Ultimately, the crux of elimination remains unchanged over the past 25 years and resides in screening and diagnosis with effective linkage to care.

Donald M. Jensen, MD, is a professor of medicine at Rush University Medical Center, Chicago. He was previously the director of the Center for Liver Disease at the University of Chicago until 2015. His research interest has been in newer HCV therapies. He recently received the Distinguished Service Award from the AASLD for his many contributions to the field.

Nancy S. Reau, MD, is chief of the hepatology section at Rush University Medical Center and a regular contributor to Medscape. She serves as editor of Clinical Liver Disease, a multimedia review journal, and recently as a member of HCVGuidelines.org, a web-based resource from the AASLD and the IDSA, as well as educational chair for the AASLD hepatitis C special interest group. She continues to have an active role in the hepatology interest group of the World Gastroenterology Organisation and the American Liver Foundation at the regional and national levels.
 

References

Woolley AE et al. Heart and lung transplants from HCV-infected donors to uninfected recipients. N Engl J Med. 2019;380:1606-17.

Franco A et al. Renal transplantation from seropositive hepatitis C virus donors to seronegative recipients in Spain: A prospective study. Transpl Int. 2019;32:710-6.

Goldberg DS et al. Transplanting HCV-infected kidneys into uninfected recipients. N Engl J Med. 2017;377:1105.

Kwong AJ et al. Liver transplantation for hepatitis C virus (HCV) nonviremic recipients with HCV viremic donors. Am J Transplant. 2019;19:1380-7.

Bethea E et al. Immediate administration of antiviral therapy after transplantation of hepatitis C–infected livers into uninfected recipients: Implications for therapeutic planning. Am J Transplant. 2020;20:1619-28.

This article first appeared on Medscape.com.

One of the most remarkable stories in medicine must be the relatively brief 25 years between the discovery of the hepatitis C virus (HCV) in 1989 to its eventual cure in 2014.

HCV afflicted over 5 million Americans and was the cause of death in approximately 10,000 patients annually, the leading indication for liver transplantation, and the leading risk factor for hepatocellular carcinoma, clearly signaling it as one of the era’s major public health villains. Within that span of time, it is the work beginning in the mid-1990s until today that perhaps best defines the race for the HCV “cure.”

In the early to mid-1990s, polymerase chain reaction techniques were just becoming commonplace for HCV diagnosis, whereas HCV genotypes were emerging as major factors determining response to interferon therapy. The sustained viral response (SVR) rates were mired at around 6%-12% for a 24- to 48-week course of three-times-weekly injection therapy. Severe side effects were common and there was a relatively high relapse rate, even in patients who responded to treatment.

By 1996, the addition of ribavirin to the interferon treatment was associated with a modest but significant improvement in SVR rates to above 20%. And by 2000, the use of pegylated interferon – allowing once-weekly injection therapy – along with ribavirin, improved SVR rates to above 50% for the first time. The therapy was still poorly tolerated but was associated with better compliance.

The real breakthrough in therapy came in the early 2000s with the discovery and availability of HCV protease inhibitors: telaprevir and boceprevir. These agents could induce a more rapid decline in viral replication than interferon but could not be administered alone owing to the rapid emergence of resistant HCV variants. Therefore, these agents were administered with interferon and ribavirin as a three-drug cocktail to take advantage of interferon to prevent emergence of resistant variants. Although SVR rates improved substantially to around 75%, adverse events also increased and limited its usefulness in patients with more advanced liver disease, precisely those who were most in need of better therapies.

Nonetheless, the incredible advances in understanding the replication machinery of HCV that led to the discovery of the protease inhibitors in turn led to further elucidation and unlocking of three additional classes of HCV protein targets and inhibitors: NS5A complex inhibitors (e.g., ledipasvir), the NS5B nonnucleoside inhibitors (e.g., dasabuvir), and NS5B nucleoside inhibitors (e.g., sofosbuvir). It quickly became apparent that the use of combinations of these direct-acting antivirals (DAAs) could limit emergence of resistant variants while also providing rapid and profound viral suppression. Because HCV required viral replication to persist in the hepatocyte, it became possible to induce HCV eradication, and thus cure, with combinations of DAAs.

In addition, investigators soon learned that the duration of therapy no longer needed to be the generally accepted 24-48 weeks for SVR, but instead could be reduced eventually to 8-12 weeks. This shortened treatment duration allowed for more rapid testing of new agents and combinations, and the field took a rapid step forward between 2011 and 2017. HCV cure rates rose to 90%-95%.

The competition for Food and Drug Administration approval of new agents among several pharmaceutical companies also meant that the time-honored process of issuing treatment guidelines every 3-5 years by societies would not be adequate. Therefore, in 2013, the American Association for the Study of Liver Diseases and the Infectious Diseases Society of America joined forces to establish more nimble and responsive online HCV guidance. This important resource debuted in January 2014 just as the FDA approved the first DAA therapies.

The high cost initially associated with many of these new therapies (up to $1,000 per pill) significantly limited uptake owing to insurance and health plan cost factors. Early on, the cost was also analyzed by price per cure, seemingly to justify the high cost by the high cure rate. However, advocacy and negotiations ultimately led to marked reductions in the cost of a course of therapy (with some therapies at $225 per pill), thus making these treatments now widely available.

By 2020, the HCV field has shifted from therapeutic development to improving the care cascade by enhanced identification and testing of unsuspected but HCV infected individuals. This is our current challenge.
 

Moving toward noninvasive tests

While curative therapy has revolutionized HCV management, innovation in diagnostics eliminated a significant barrier in access to therapy: the liver biopsy.

Staging, or accurately identifying advanced fibrosis in persons infected with HCV, is essential for long-term follow-up. The presence of advanced disease affects drug choices, especially before the approval of all-oral therapy. Historically, a liver biopsy was obligatory before treatment. Invasive with a significant risk for complications, this requirement effectively prevented treatment in those who were unwilling to undergo the procedure and deterred those at risk from even being tested.

Over the past 25 years, numerous methods to noninvasively assess for liver fibrosis have been used. Serum biomarkers can be either indirect (based on routine tests) or direct (reflecting components of the extracellular matrix). Although highly available, they are only moderately useful for identifying advanced fibrosis and thus cannot replace liver biopsy in the care cascade. The technique of elastography dates back to the 1980s, though the role of vibration-controlled transient liver elastography in the assessment of hepatic fibrosis in patients with HCV was not recognized until around 2005 and it was not commonly used for nearly another decade.

Yet, a paradigm shift in the care cascade occurred with the release of the AASLD/IDSA guidance document in 2014. For the first time in the United States, noninvasive tests were recommended as first-line testing for the assessment of advanced fibrosis. Prior guidelines specifically stated that although noninvasive tests might be useful, they “should not replace the liver biopsy in routine clinical practice.” Current guidelines recommend combining elastography with serum biomarkers and considering biopsy only in patients with discordant results if the biopsy would affect clinical decision-making.
 

The last frontier

Curative therapy has also allowed the unthinkable: willingly exposing patients to the virus through donor-positive/recipient-negative solid organ transplant. Traditionally, an HCV-infected donor would be considered only for an HCV-positive recipient; however, with effective DAA therapy, the number of HCV actively infected patients in need of transplant has dwindled.

Unfortunately as a consequence of the opioid epidemic, the HCV-exposed donor population has blossomed. Given that HCV therapy is near universally curative, using organs from HCV-viremic donors can greatly expand the organ transplantation pool. Small studies[1-5] have demonstrated the safety and efficacy of this approach, both in HCV-positive liver donors as well as in other solid organs.
 

A disease pegged for elimination

In the past 25 years, HCV has evolved from non-A, non-B hepatitis into a disease pegged for elimination. This is a direct reflection of improved therapeutics with highly effective DAAs. Yet, without improved diagnostics, we would be unable to navigate patients through the clinical care cascade. These incredible strides in diagnostics and therapeutics allow us to push the cutting edge through iatrogenic infection of organ recipients, while recognizing that the largest hurdle to elimination remains in finding those who are chronically infected. Ultimately, the crux of elimination remains unchanged over the past 25 years and resides in screening and diagnosis with effective linkage to care.

Donald M. Jensen, MD, is a professor of medicine at Rush University Medical Center, Chicago. He was previously the director of the Center for Liver Disease at the University of Chicago until 2015. His research interest has been in newer HCV therapies. He recently received the Distinguished Service Award from the AASLD for his many contributions to the field.

Nancy S. Reau, MD, is chief of the hepatology section at Rush University Medical Center and a regular contributor to Medscape. She serves as editor of Clinical Liver Disease, a multimedia review journal, and recently as a member of HCVGuidelines.org, a web-based resource from the AASLD and the IDSA, as well as educational chair for the AASLD hepatitis C special interest group. She continues to have an active role in the hepatology interest group of the World Gastroenterology Organisation and the American Liver Foundation at the regional and national levels.
 

References

Woolley AE et al. Heart and lung transplants from HCV-infected donors to uninfected recipients. N Engl J Med. 2019;380:1606-17.

Franco A et al. Renal transplantation from seropositive hepatitis C virus donors to seronegative recipients in Spain: A prospective study. Transpl Int. 2019;32:710-6.

Goldberg DS et al. Transplanting HCV-infected kidneys into uninfected recipients. N Engl J Med. 2017;377:1105.

Kwong AJ et al. Liver transplantation for hepatitis C virus (HCV) nonviremic recipients with HCV viremic donors. Am J Transplant. 2019;19:1380-7.

Bethea E et al. Immediate administration of antiviral therapy after transplantation of hepatitis C–infected livers into uninfected recipients: Implications for therapeutic planning. Am J Transplant. 2020;20:1619-28.

This article first appeared on Medscape.com.

The incidence rate of hepatocellular carcinoma in urban areas of the United States began to slow in 2009, but the rate in rural areas of the nation continued to rise at a steady pace, especially among non-Hispanic Whites and Blacks, investigators have found.

Although overall hepatocellular carcinoma (HCC) incidence rates were consistently lower among people living in nonmetro (rural) versus metro (urban) areas, the average annual percentage change in urban areas began to slow from 5.3% for the period of 1995 through 2009 to 2.7% thereafter. In contrast, the average annual percentage change in rural areas remained steady at 5.7%, a disparity that remained even after adjusting for differences among subgroups, reported Christina Gainey, MD, a third-year resident in internal medicine at the University of Southern California Medical Center, Los Angeles.

“We found that there are striking urban-rural disparities in HCC incidence trends that vary by race and ethnicity, and these disparities are growing over time,” she said during the virtual annual meeting of the American Association for the Study of Liver Diseases.

“Our study really highlights a critical public health issue that’s disproportionately affecting rural Americans. They already face considerable health inequities when it comes to access to care, health outcomes, and public health infrastructure and resources, and as of now we still don’t know why cases of HCC continue to rise in these areas,” she said.

Dr. Gainey noted that HCC is the fastest-growing cancer in the United States, according to the 2020 Annual Report to the Nation on the Status of Cancer, issued jointly by the Centers for Disease Control and Prevention, the North American Association of Central Cancer Registries, the American Cancer Society, and the National Cancer Institute.

Previous studies have identified disparities between urban and rural regions in care of patients with cervical cancer, colorectal cancer, and other malignancies, but there are very few data on urban-rural differences in HCC incidence, she said.
 

Incidence trends

To better understand whether such differences exists, the investigators compared trends in age-adjusted incidence rates of HCC in both rural and urban areas of the United States from 1995 to 2016, with stratification of trends by race/ethnicity and other demographic factors.

They drew from the NAACR database, which captures 93% of the U.S. population, in contrast to the CDC’s Surveillance, Epidemiology, and End Results (SEER) database which samples just 18% of the population.

Patients with HCC were defined by diagnostic codes, with diagnoses of intrahepatic bile duct cancers excluded.

They used 2013 U.S. Department of Agriculture Rural-Urban Continuum Codes to identify rural areas (regions of open countryside with town populations fewer than 2,500 people) and urban areas (populations ranging from 2,500 to 49,999, but not part of a larger labor market area).

The investigators identified a total of 310,635 HCC cases, 85% in urban areas and 15% in rural areas. Three-fourths of the patients (77%) were male. The median age ranged from 55-59 years.

There were notable demographic differences between the regions with non-Hispanic Whites comprising only 57% of the urban sample, but 82% of the rural sample. The urban sample included 16% non-Hispanic Blacks, 10% Asian/Pacific Islanders, and 17% Hispanics. The respective proportions in the rural areas were 8%, 2%, and 8%.

As noted before, age-adjusted incidence rates (adjusted to the year 2000 U.S. population) were lower in rural areas, at 4.9 per 100,000 population, compared with 6.9/100,000 in urban areas.

But when they looked at the average annual percentage changes using jointpoint regression, they saw that beginning in 2009 the AAPC in urban areas began to slow, from 5.3% for the period prior to 2009 to 2.7% thereafter, while the average annual percentage change in urban areas remained steady at 5.7%.

The largest increase in incidence over the course of the study was among rural non-Hispanic Whites, with an AAPC of 5.7%. Among urban non-Hispanic Blacks, the AAPC rose by 6.6% from 1995 to 2009, but slowed thereafter.

In contrast, among rural non-Hispanic Blacks the AAPC remained steady, at 5.4%.

The only group to see a decline in incidence was urban Asians/Pacific Islanders, who had an overall decline of 1%.

Among all groups, rural Hispanics had the highest age-adjusted incidence rates, at 14.9 per 100,000 in 2016.
 

Awareness gap?

 Lewis R. Roberts, MB, ChB, PhD, a hepatobiliary cancer researcher at the Mayo Clinic in Rochester, Minn., who was not involved in the study, said in an interview that the difference in incidence rates between cities and the country may be attributable to a number of factors, including the opioid crisis, which can lead to an increase in injectable drug use or sexual behaviors resulting in increases in chronic hepatitis C infections and cirrhosis, known risk factors for HCC, as well as a lack of awareness of infections as a risk factor.

“In order for people to find these diseases, they have to be looking, and many of these are hidden diseases in our community,” he said. “What the study made me wonder was whether it just happens to be that they are in some ways more hidden in a rural community than they are in an urban community.”

He noted that clinicians in urban communities are more accustomed to treating more diverse populations who may have higher susceptibility to viral hepatitis, for example, and that screening and treatment for hepatitis C may be more common in urban areas than rural areas, he said.

No funding source for the study was reported. Dr. Gainey and Dr. Roberts reported having no conflicts of interest to disclose.

SOURCE: Gainey C et al. Liver Meeting 2020, Abstract 136.

The incidence rate of hepatocellular carcinoma in urban areas of the United States began to slow in 2009, but the rate in rural areas of the nation continued to rise at a steady pace, especially among non-Hispanic Whites and Blacks, investigators have found.

Although overall hepatocellular carcinoma (HCC) incidence rates were consistently lower among people living in nonmetro (rural) versus metro (urban) areas, the average annual percentage change in urban areas began to slow from 5.3% for the period of 1995 through 2009 to 2.7% thereafter. In contrast, the average annual percentage change in rural areas remained steady at 5.7%, a disparity that remained even after adjusting for differences among subgroups, reported Christina Gainey, MD, a third-year resident in internal medicine at the University of Southern California Medical Center, Los Angeles.

“We found that there are striking urban-rural disparities in HCC incidence trends that vary by race and ethnicity, and these disparities are growing over time,” she said during the virtual annual meeting of the American Association for the Study of Liver Diseases.

“Our study really highlights a critical public health issue that’s disproportionately affecting rural Americans. They already face considerable health inequities when it comes to access to care, health outcomes, and public health infrastructure and resources, and as of now we still don’t know why cases of HCC continue to rise in these areas,” she said.

Dr. Gainey noted that HCC is the fastest-growing cancer in the United States, according to the 2020 Annual Report to the Nation on the Status of Cancer, issued jointly by the Centers for Disease Control and Prevention, the North American Association of Central Cancer Registries, the American Cancer Society, and the National Cancer Institute.

Previous studies have identified disparities between urban and rural regions in care of patients with cervical cancer, colorectal cancer, and other malignancies, but there are very few data on urban-rural differences in HCC incidence, she said.
 

Incidence trends

To better understand whether such differences exists, the investigators compared trends in age-adjusted incidence rates of HCC in both rural and urban areas of the United States from 1995 to 2016, with stratification of trends by race/ethnicity and other demographic factors.

They drew from the NAACR database, which captures 93% of the U.S. population, in contrast to the CDC’s Surveillance, Epidemiology, and End Results (SEER) database which samples just 18% of the population.

Patients with HCC were defined by diagnostic codes, with diagnoses of intrahepatic bile duct cancers excluded.

They used 2013 U.S. Department of Agriculture Rural-Urban Continuum Codes to identify rural areas (regions of open countryside with town populations fewer than 2,500 people) and urban areas (populations ranging from 2,500 to 49,999, but not part of a larger labor market area).

The investigators identified a total of 310,635 HCC cases, 85% in urban areas and 15% in rural areas. Three-fourths of the patients (77%) were male. The median age ranged from 55-59 years.

There were notable demographic differences between the regions with non-Hispanic Whites comprising only 57% of the urban sample, but 82% of the rural sample. The urban sample included 16% non-Hispanic Blacks, 10% Asian/Pacific Islanders, and 17% Hispanics. The respective proportions in the rural areas were 8%, 2%, and 8%.

As noted before, age-adjusted incidence rates (adjusted to the year 2000 U.S. population) were lower in rural areas, at 4.9 per 100,000 population, compared with 6.9/100,000 in urban areas.

But when they looked at the average annual percentage changes using jointpoint regression, they saw that beginning in 2009 the AAPC in urban areas began to slow, from 5.3% for the period prior to 2009 to 2.7% thereafter, while the average annual percentage change in urban areas remained steady at 5.7%.

The largest increase in incidence over the course of the study was among rural non-Hispanic Whites, with an AAPC of 5.7%. Among urban non-Hispanic Blacks, the AAPC rose by 6.6% from 1995 to 2009, but slowed thereafter.

In contrast, among rural non-Hispanic Blacks the AAPC remained steady, at 5.4%.

The only group to see a decline in incidence was urban Asians/Pacific Islanders, who had an overall decline of 1%.

Among all groups, rural Hispanics had the highest age-adjusted incidence rates, at 14.9 per 100,000 in 2016.
 

Awareness gap?

 Lewis R. Roberts, MB, ChB, PhD, a hepatobiliary cancer researcher at the Mayo Clinic in Rochester, Minn., who was not involved in the study, said in an interview that the difference in incidence rates between cities and the country may be attributable to a number of factors, including the opioid crisis, which can lead to an increase in injectable drug use or sexual behaviors resulting in increases in chronic hepatitis C infections and cirrhosis, known risk factors for HCC, as well as a lack of awareness of infections as a risk factor.

“In order for people to find these diseases, they have to be looking, and many of these are hidden diseases in our community,” he said. “What the study made me wonder was whether it just happens to be that they are in some ways more hidden in a rural community than they are in an urban community.”

He noted that clinicians in urban communities are more accustomed to treating more diverse populations who may have higher susceptibility to viral hepatitis, for example, and that screening and treatment for hepatitis C may be more common in urban areas than rural areas, he said.

No funding source for the study was reported. Dr. Gainey and Dr. Roberts reported having no conflicts of interest to disclose.

SOURCE: Gainey C et al. Liver Meeting 2020, Abstract 136.

The incidence rate of hepatocellular carcinoma in urban areas of the United States began to slow in 2009, but the rate in rural areas of the nation continued to rise at a steady pace, especially among non-Hispanic Whites and Blacks, investigators have found.

Although overall hepatocellular carcinoma (HCC) incidence rates were consistently lower among people living in nonmetro (rural) versus metro (urban) areas, the average annual percentage change in urban areas began to slow from 5.3% for the period of 1995 through 2009 to 2.7% thereafter. In contrast, the average annual percentage change in rural areas remained steady at 5.7%, a disparity that remained even after adjusting for differences among subgroups, reported Christina Gainey, MD, a third-year resident in internal medicine at the University of Southern California Medical Center, Los Angeles.

“We found that there are striking urban-rural disparities in HCC incidence trends that vary by race and ethnicity, and these disparities are growing over time,” she said during the virtual annual meeting of the American Association for the Study of Liver Diseases.

“Our study really highlights a critical public health issue that’s disproportionately affecting rural Americans. They already face considerable health inequities when it comes to access to care, health outcomes, and public health infrastructure and resources, and as of now we still don’t know why cases of HCC continue to rise in these areas,” she said.

Dr. Gainey noted that HCC is the fastest-growing cancer in the United States, according to the 2020 Annual Report to the Nation on the Status of Cancer, issued jointly by the Centers for Disease Control and Prevention, the North American Association of Central Cancer Registries, the American Cancer Society, and the National Cancer Institute.

Previous studies have identified disparities between urban and rural regions in care of patients with cervical cancer, colorectal cancer, and other malignancies, but there are very few data on urban-rural differences in HCC incidence, she said.
 

Incidence trends

To better understand whether such differences exists, the investigators compared trends in age-adjusted incidence rates of HCC in both rural and urban areas of the United States from 1995 to 2016, with stratification of trends by race/ethnicity and other demographic factors.

They drew from the NAACR database, which captures 93% of the U.S. population, in contrast to the CDC’s Surveillance, Epidemiology, and End Results (SEER) database which samples just 18% of the population.

Patients with HCC were defined by diagnostic codes, with diagnoses of intrahepatic bile duct cancers excluded.

They used 2013 U.S. Department of Agriculture Rural-Urban Continuum Codes to identify rural areas (regions of open countryside with town populations fewer than 2,500 people) and urban areas (populations ranging from 2,500 to 49,999, but not part of a larger labor market area).

The investigators identified a total of 310,635 HCC cases, 85% in urban areas and 15% in rural areas. Three-fourths of the patients (77%) were male. The median age ranged from 55-59 years.

There were notable demographic differences between the regions with non-Hispanic Whites comprising only 57% of the urban sample, but 82% of the rural sample. The urban sample included 16% non-Hispanic Blacks, 10% Asian/Pacific Islanders, and 17% Hispanics. The respective proportions in the rural areas were 8%, 2%, and 8%.

As noted before, age-adjusted incidence rates (adjusted to the year 2000 U.S. population) were lower in rural areas, at 4.9 per 100,000 population, compared with 6.9/100,000 in urban areas.

But when they looked at the average annual percentage changes using jointpoint regression, they saw that beginning in 2009 the AAPC in urban areas began to slow, from 5.3% for the period prior to 2009 to 2.7% thereafter, while the average annual percentage change in urban areas remained steady at 5.7%.

The largest increase in incidence over the course of the study was among rural non-Hispanic Whites, with an AAPC of 5.7%. Among urban non-Hispanic Blacks, the AAPC rose by 6.6% from 1995 to 2009, but slowed thereafter.

In contrast, among rural non-Hispanic Blacks the AAPC remained steady, at 5.4%.

The only group to see a decline in incidence was urban Asians/Pacific Islanders, who had an overall decline of 1%.

Among all groups, rural Hispanics had the highest age-adjusted incidence rates, at 14.9 per 100,000 in 2016.
 

Awareness gap?

 Lewis R. Roberts, MB, ChB, PhD, a hepatobiliary cancer researcher at the Mayo Clinic in Rochester, Minn., who was not involved in the study, said in an interview that the difference in incidence rates between cities and the country may be attributable to a number of factors, including the opioid crisis, which can lead to an increase in injectable drug use or sexual behaviors resulting in increases in chronic hepatitis C infections and cirrhosis, known risk factors for HCC, as well as a lack of awareness of infections as a risk factor.

“In order for people to find these diseases, they have to be looking, and many of these are hidden diseases in our community,” he said. “What the study made me wonder was whether it just happens to be that they are in some ways more hidden in a rural community than they are in an urban community.”

He noted that clinicians in urban communities are more accustomed to treating more diverse populations who may have higher susceptibility to viral hepatitis, for example, and that screening and treatment for hepatitis C may be more common in urban areas than rural areas, he said.

No funding source for the study was reported. Dr. Gainey and Dr. Roberts reported having no conflicts of interest to disclose.

SOURCE: Gainey C et al. Liver Meeting 2020, Abstract 136.

Individuals living with hepatitis C virus (HCV) infection face several challenges in accessing care, many of which are shared by patients in the HIV community.

Better linkage to care with providers who are familiar with both the HCV and HIV treatment cascade may not only improve access to HCV treatment, but it may also support patient retention, treatment adherence, and achievement of sustained virologic response (SVR) and viral suppression, said Stephanie LaMoy, CAN Community Health, North Point, Florida. She presented the results of a pilot study at the virtual Association of Nurses in AIDS Care 2020 Annual Meeting.

In an effort to identify strategies most important for improving care access among their patients with HCV, LaMoy and her colleagues assessed 12-month patient data collected from three of their clinics. These data were evaluated for HCV treatment access, engagement, and outcomes.

The pilot study included 126 patients who were reactive and another 24 HCV-positive patients who were referred from other sources. Active HCV infections requiring treatment were reported in 144 patients.

A total of 59 patients were linked to care but did not initiate treatment for their active infection. LaMoy said there were multiple causes, including homelessness, substance abuse, and inability to maintain contact.

In contrast, 85 patients with HCV infection started treatment, but 35 of these patients did not complete their regimen. Out of the 50 patients who reported completing treatment, 30 did not return to the clinic to confirm sustained viral suppression.

According to LaMoy, this raised a red flag, causing the investigators to consider a different approach to care.
 

HIV care continuum model and its role in HCV

To improve the rate at which patients with HCV infection complete treatment within their clinics, the researchers formed a panel to determine necessary interventions that could reduce barriers to care.

The HIV care continuum came into play. They chose this model based on knowledge that HCV and HIV share the same care continuum with similar goals in diagnosis, linkage to care, retention, and suppression.

Based on the consensus of the panel and consideration of the HIV care continuum model, they identified a number of interventions needed to mitigate HCV treatment barriers. These included the incorporation of peer navigators or linkage-to-care (LCC) coordinators, use of the mobile medical unit, greater implementation of onsite lab visits, and medication-assisted treatment.

The LCC coordinators proved to be particularly important, as these team members helped assist patients with social and financial support to address challenges with access to treatment. These coordinators can also help  patients gain access to specialized providers, ultimately improving the chance of successful HCV management.

Additionally, LCC coordinators may help identify and reduce barriers associated with housing, transportation, and nutrition. Frequent patient contact by the LCC coordinators can encourage adherence and promote risk reduction education, such as providing referrals to needle exchange services.

“Linking individuals to care with providers who are familiar with the treatment cascade could help improve retention and should be a top priority for those involved in HCV screening and treatment,” said LaMoy. “An environment with knowledge, lack of judgment, and a tenacious need to heal the community that welcomes those with barriers to care is exactly what is needed for the patients in our program.”
 

National, community challenges fuel barriers to HCV treatment access

Substance use, trauma histories, and mental health problems can negatively affect care engagement and must be addressed before the benefits of HCV therapy can be realized.

Addressing these issues isn’t always easy, said Kathleen Bernock, FNP-BC, AACRN, AAHIVS, of the Bedford-Stuyvesant Family Health Center in New York City, in an email to Medscape Medical News. She pointed out that several states have harsh restrictions on who is able to access HCV treatment, and some states will not approve certain medications for people who actively use drugs.

“Even for states without these restrictions, many health systems are difficult to navigate and may not be welcoming to persons actively using,” said Bernock. Trauma-informed care can also be difficult to translate into clinics, she added.

“Decentralizing care to the communities most affected would greatly help mitigate these barriers,” suggested Bernock. Decentralization, she explained, might include co-locating services such as syringe exchanges, utilizing community health workers and patient navigators, and expanding capacity-to-treat to community-based providers.

“[And] with the expansion of telehealth services in the US,” said Bernock, “we now have even more avenues to reach people that we never had before.”

LaMoy and Bernock have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Individuals living with hepatitis C virus (HCV) infection face several challenges in accessing care, many of which are shared by patients in the HIV community.

Better linkage to care with providers who are familiar with both the HCV and HIV treatment cascade may not only improve access to HCV treatment, but it may also support patient retention, treatment adherence, and achievement of sustained virologic response (SVR) and viral suppression, said Stephanie LaMoy, CAN Community Health, North Point, Florida. She presented the results of a pilot study at the virtual Association of Nurses in AIDS Care 2020 Annual Meeting.

In an effort to identify strategies most important for improving care access among their patients with HCV, LaMoy and her colleagues assessed 12-month patient data collected from three of their clinics. These data were evaluated for HCV treatment access, engagement, and outcomes.

The pilot study included 126 patients who were reactive and another 24 HCV-positive patients who were referred from other sources. Active HCV infections requiring treatment were reported in 144 patients.

A total of 59 patients were linked to care but did not initiate treatment for their active infection. LaMoy said there were multiple causes, including homelessness, substance abuse, and inability to maintain contact.

In contrast, 85 patients with HCV infection started treatment, but 35 of these patients did not complete their regimen. Out of the 50 patients who reported completing treatment, 30 did not return to the clinic to confirm sustained viral suppression.

According to LaMoy, this raised a red flag, causing the investigators to consider a different approach to care.
 

HIV care continuum model and its role in HCV

To improve the rate at which patients with HCV infection complete treatment within their clinics, the researchers formed a panel to determine necessary interventions that could reduce barriers to care.

The HIV care continuum came into play. They chose this model based on knowledge that HCV and HIV share the same care continuum with similar goals in diagnosis, linkage to care, retention, and suppression.

Based on the consensus of the panel and consideration of the HIV care continuum model, they identified a number of interventions needed to mitigate HCV treatment barriers. These included the incorporation of peer navigators or linkage-to-care (LCC) coordinators, use of the mobile medical unit, greater implementation of onsite lab visits, and medication-assisted treatment.

The LCC coordinators proved to be particularly important, as these team members helped assist patients with social and financial support to address challenges with access to treatment. These coordinators can also help  patients gain access to specialized providers, ultimately improving the chance of successful HCV management.

Additionally, LCC coordinators may help identify and reduce barriers associated with housing, transportation, and nutrition. Frequent patient contact by the LCC coordinators can encourage adherence and promote risk reduction education, such as providing referrals to needle exchange services.

“Linking individuals to care with providers who are familiar with the treatment cascade could help improve retention and should be a top priority for those involved in HCV screening and treatment,” said LaMoy. “An environment with knowledge, lack of judgment, and a tenacious need to heal the community that welcomes those with barriers to care is exactly what is needed for the patients in our program.”
 

National, community challenges fuel barriers to HCV treatment access

Substance use, trauma histories, and mental health problems can negatively affect care engagement and must be addressed before the benefits of HCV therapy can be realized.

Addressing these issues isn’t always easy, said Kathleen Bernock, FNP-BC, AACRN, AAHIVS, of the Bedford-Stuyvesant Family Health Center in New York City, in an email to Medscape Medical News. She pointed out that several states have harsh restrictions on who is able to access HCV treatment, and some states will not approve certain medications for people who actively use drugs.

“Even for states without these restrictions, many health systems are difficult to navigate and may not be welcoming to persons actively using,” said Bernock. Trauma-informed care can also be difficult to translate into clinics, she added.

“Decentralizing care to the communities most affected would greatly help mitigate these barriers,” suggested Bernock. Decentralization, she explained, might include co-locating services such as syringe exchanges, utilizing community health workers and patient navigators, and expanding capacity-to-treat to community-based providers.

“[And] with the expansion of telehealth services in the US,” said Bernock, “we now have even more avenues to reach people that we never had before.”

LaMoy and Bernock have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Individuals living with hepatitis C virus (HCV) infection face several challenges in accessing care, many of which are shared by patients in the HIV community.

Better linkage to care with providers who are familiar with both the HCV and HIV treatment cascade may not only improve access to HCV treatment, but it may also support patient retention, treatment adherence, and achievement of sustained virologic response (SVR) and viral suppression, said Stephanie LaMoy, CAN Community Health, North Point, Florida. She presented the results of a pilot study at the virtual Association of Nurses in AIDS Care 2020 Annual Meeting.

In an effort to identify strategies most important for improving care access among their patients with HCV, LaMoy and her colleagues assessed 12-month patient data collected from three of their clinics. These data were evaluated for HCV treatment access, engagement, and outcomes.

The pilot study included 126 patients who were reactive and another 24 HCV-positive patients who were referred from other sources. Active HCV infections requiring treatment were reported in 144 patients.

A total of 59 patients were linked to care but did not initiate treatment for their active infection. LaMoy said there were multiple causes, including homelessness, substance abuse, and inability to maintain contact.

In contrast, 85 patients with HCV infection started treatment, but 35 of these patients did not complete their regimen. Out of the 50 patients who reported completing treatment, 30 did not return to the clinic to confirm sustained viral suppression.

According to LaMoy, this raised a red flag, causing the investigators to consider a different approach to care.
 

HIV care continuum model and its role in HCV

To improve the rate at which patients with HCV infection complete treatment within their clinics, the researchers formed a panel to determine necessary interventions that could reduce barriers to care.

The HIV care continuum came into play. They chose this model based on knowledge that HCV and HIV share the same care continuum with similar goals in diagnosis, linkage to care, retention, and suppression.

Based on the consensus of the panel and consideration of the HIV care continuum model, they identified a number of interventions needed to mitigate HCV treatment barriers. These included the incorporation of peer navigators or linkage-to-care (LCC) coordinators, use of the mobile medical unit, greater implementation of onsite lab visits, and medication-assisted treatment.

The LCC coordinators proved to be particularly important, as these team members helped assist patients with social and financial support to address challenges with access to treatment. These coordinators can also help  patients gain access to specialized providers, ultimately improving the chance of successful HCV management.

Additionally, LCC coordinators may help identify and reduce barriers associated with housing, transportation, and nutrition. Frequent patient contact by the LCC coordinators can encourage adherence and promote risk reduction education, such as providing referrals to needle exchange services.

“Linking individuals to care with providers who are familiar with the treatment cascade could help improve retention and should be a top priority for those involved in HCV screening and treatment,” said LaMoy. “An environment with knowledge, lack of judgment, and a tenacious need to heal the community that welcomes those with barriers to care is exactly what is needed for the patients in our program.”
 

National, community challenges fuel barriers to HCV treatment access

Substance use, trauma histories, and mental health problems can negatively affect care engagement and must be addressed before the benefits of HCV therapy can be realized.

Addressing these issues isn’t always easy, said Kathleen Bernock, FNP-BC, AACRN, AAHIVS, of the Bedford-Stuyvesant Family Health Center in New York City, in an email to Medscape Medical News. She pointed out that several states have harsh restrictions on who is able to access HCV treatment, and some states will not approve certain medications for people who actively use drugs.

“Even for states without these restrictions, many health systems are difficult to navigate and may not be welcoming to persons actively using,” said Bernock. Trauma-informed care can also be difficult to translate into clinics, she added.

“Decentralizing care to the communities most affected would greatly help mitigate these barriers,” suggested Bernock. Decentralization, she explained, might include co-locating services such as syringe exchanges, utilizing community health workers and patient navigators, and expanding capacity-to-treat to community-based providers.

“[And] with the expansion of telehealth services in the US,” said Bernock, “we now have even more avenues to reach people that we never had before.”

LaMoy and Bernock have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

It took an average of 380 days for people who had received an abnormal anal Pap test result after having been diagnosed with HIV to undergo high-resolution anoscopy (HRA), which is recommended as follow-up.

That delay “revealed missed opportunities for a better experience on the patient, clinic, and provider level,” Jessica Wells, PhD, research assistant professor at the Nell Hodgson Woodruff School of Nursing at Emory University, Atlanta, said in an interview. After all, “a lot can happen in that 1 year,” including early development of human papillomavirus (HPV)–associated anal cancer.

Although it’s too soon to say how significant that delay is with respect to the natural history of anal cancer, Dr. Wells said the data are a potential signal of disparities.

“The findings from my study may foreshadow potential disparities if we don’t have the necessary resources in place to promote follow-up care after an abnormal Pap test, similar to the disparities that we see in cervical cancer,” she said during the virtual Association of Nurses in AIDS Care 2020 Annual Meeting.
 

Single-center study

In the United States, people living with HIV are 19 times more likely to develop anal cancer than the general population, according to a 2018 article in the Journal of Clinical Oncology. Another single-center study from Yale University found that, in minority communities, anal cancer rates were 75% higher than in White communities. Anal cancer rates were 72% higher in communities with greater poverty. As a result, many clinics are beginning to administer Pap tests to determine early signs of HPV infection and associated changes.

In Dr. Wells’ study, which was conducted from 2012 to 2015, 150 adults with HIV who were aged 21 and older were recruited from Grady Ponce De Leon Center in Atlanta. According to a 2018 study from that center, a large minority of participants had late-stage HIV and suppressed immune systems.

All participants had been referred for HRA after a recent abnormal anal Pap test. Participants filled out questionnaires on sociodemographics, internalized HIV-related stigma, depression, risk behaviors, social support, and knowledge about HPV and anal cancer.

Participants were disproportionately older (mean age, 50.9 years); cisgender (86.7%), Black (78%); and gay, lesbian, or bisexual (84.3%). Slightly more than 1 in 10 participants (11.3%) were transgender women.

Although for 6% of participants, Pap test results indicated high-grade squamous intraepithelial lesions (HSIL), an additional 8% had atypical Pap findings that couldn’t exclude HSIL – the kinds of results that are one step away from a cancer diagnosis. More than 80% of participants had low-grade or inconclusive results. Nearly half (44%) of participants’ Pap tests revealed low-grade squamous cell intraepithelial cell lesions (LSIL); 42% indicated atypical squamous cells of undetermined significance.

When Dr. Wells looked at how long participants had waited to undergo HRA, she found something that surprised her: although some participants underwent follow-up assessment in 17 days, for many, it took much longer. The longest wait was 2,350 days – more than 6 years.

“There were quite a few patients who had follow-up beyond 1,000-plus days,” Dr. Wells said in an interview. “I didn›t think the delays were that long — at most, I would say that patients will get scheduled and come back within a few weeks or months.”

What’s more, she discovered through the HPV knowledge questionnaire that many participants did not understand why they were having a follow-up appointment. Anecdotally, some confused HPV with HIV.

“There’s education to be done to inform this target population that those living with HIV are more prone or at increased risk of this virus causing cancer later,” she said. “There are a lot of campaigns around women living with HIV, that they need to do cervical cancer screening. I think we need to really expand this campaign to include that HPV can also cause anal cancer.”

Dr. Wells had planned to primarily investigate the impact of psychosocial factors on wait time to follow-up, but none of those factors were associated with longer wait times.
 

Systems-level factors

That led Ann Gakumo, PhD, chair of nursing at the College of Nursing and Health Sciences of the University of Massachusetts, Boston, to ask what other factors could account for the delay.

There were several, Dr. Wells said. Precarious housing, for example, could have influenced this lag in follow-up. About one in four participants were in transient housing, and one participant reported having been incarcerated. She gathered street addresses and plans to analyze that data to see whether the cases occurred in clusters in specific neighborhoods, as the Yale data indicated.

In addition, the anoscopy clinic was only available to receive patients one day a week and was staffed with only one clinician who was trained to perform HRA. Wait times could stretch for hours. Sometimes, participants had to leave the clinic to attend to other business, and their appointments needed to be rescheduled, Wells said.

In addition to the sometimes poor understanding of the importance of the follow-up test, Dr. Wells said, “we start to see a layering of these barriers. That’s where we start seeing breakdowns. So I’m hoping in a larger study I can address some of these barriers on a multilevel approach.”

This resonated with Dr. Gakumo.

“Oftentimes, we put so much of the responsibility for this on the part of the client and not enough on the part of the provider or on the systems level,” she said.
 

Guiding guidelines

Guidelines on follow-up for abnormal anal Pap test results are scarce, mostly because, unlike cervical cancer, the natural history of HPV-related anal cancers hasn’t been established. The HIV Medical Association does recommend anal Pap tests, but only in cases in which “access to appropriate referral for follow-up, including high-resolution anoscopy, is available.”

In an interview, Cecile Lahiri, MD, assistant professor of infectious disease at Emory University, said that, at Ponce De Leon Center, they recommend an anal Pap for women with HIV who have a history of cervical dysplasia.

There is a reliable association between high-grade abnormal Pap tests and cervical cancer, although low-grade changes can resolve on their own. In the case of anal cancer, especially in patients with HIV, low-grade cell changes are predictive; moreover, for such patients, anal cancer is more likely to recur and is harder to treat, Dr. Lahiri said.

“The cervical environment and the anal environment are very different,” said Dr. Lahiri, who works at the Grady Ponce De Leon Center but was not involved in Dr. Wells’ study. Dr. Lahiri is also a coinvestigator of the multisite, randomized, controlled Anal Cancer HSIL Outcomes Research (ANCHOR) study, which seeks to establish whether early treatment of high-grade anal Pap changes is better than a watch-and-wait approach.

Dr. Lahiri said that when the results of that trial become available, they are more likely to know how important early anoscopy and treatment are. The findings should inform guidelines and insurance coverage of anal Pap tests and anoscopy.

In the meantime, she said, she suspected that, with the ANCHOR trial in 2015, many sites’ capacity for anoscopy may have increased, and the wait times may have gone down.

“One of the most important pieces of the study is actually the time period in which it was conducted,” said Dr. Lahiri, who in 2015 became the clinic’s second physician trained in anoscopy. Currently, more than 200 people at the Ponce De Leon Center are enrolled in the ANCHOR trial. In addition, the general capacity for performing anoscopies has gone up nationwide as a result of the trial, which required that more providers learn how to properly perform an HRA. Many clinicians are not routinely trained in performing HRA, including gastroenterologists and surgeons, Dr. Lahiri said.

“It would be interesting to look at the differences, with the start of ANCHOR being the time point for before and after,” she said.

This article first appeared on Medscape.com.

It took an average of 380 days for people who had received an abnormal anal Pap test result after having been diagnosed with HIV to undergo high-resolution anoscopy (HRA), which is recommended as follow-up.

That delay “revealed missed opportunities for a better experience on the patient, clinic, and provider level,” Jessica Wells, PhD, research assistant professor at the Nell Hodgson Woodruff School of Nursing at Emory University, Atlanta, said in an interview. After all, “a lot can happen in that 1 year,” including early development of human papillomavirus (HPV)–associated anal cancer.

Although it’s too soon to say how significant that delay is with respect to the natural history of anal cancer, Dr. Wells said the data are a potential signal of disparities.

“The findings from my study may foreshadow potential disparities if we don’t have the necessary resources in place to promote follow-up care after an abnormal Pap test, similar to the disparities that we see in cervical cancer,” she said during the virtual Association of Nurses in AIDS Care 2020 Annual Meeting.
 

Single-center study

In the United States, people living with HIV are 19 times more likely to develop anal cancer than the general population, according to a 2018 article in the Journal of Clinical Oncology. Another single-center study from Yale University found that, in minority communities, anal cancer rates were 75% higher than in White communities. Anal cancer rates were 72% higher in communities with greater poverty. As a result, many clinics are beginning to administer Pap tests to determine early signs of HPV infection and associated changes.

In Dr. Wells’ study, which was conducted from 2012 to 2015, 150 adults with HIV who were aged 21 and older were recruited from Grady Ponce De Leon Center in Atlanta. According to a 2018 study from that center, a large minority of participants had late-stage HIV and suppressed immune systems.

All participants had been referred for HRA after a recent abnormal anal Pap test. Participants filled out questionnaires on sociodemographics, internalized HIV-related stigma, depression, risk behaviors, social support, and knowledge about HPV and anal cancer.

Participants were disproportionately older (mean age, 50.9 years); cisgender (86.7%), Black (78%); and gay, lesbian, or bisexual (84.3%). Slightly more than 1 in 10 participants (11.3%) were transgender women.

Although for 6% of participants, Pap test results indicated high-grade squamous intraepithelial lesions (HSIL), an additional 8% had atypical Pap findings that couldn’t exclude HSIL – the kinds of results that are one step away from a cancer diagnosis. More than 80% of participants had low-grade or inconclusive results. Nearly half (44%) of participants’ Pap tests revealed low-grade squamous cell intraepithelial cell lesions (LSIL); 42% indicated atypical squamous cells of undetermined significance.

When Dr. Wells looked at how long participants had waited to undergo HRA, she found something that surprised her: although some participants underwent follow-up assessment in 17 days, for many, it took much longer. The longest wait was 2,350 days – more than 6 years.

“There were quite a few patients who had follow-up beyond 1,000-plus days,” Dr. Wells said in an interview. “I didn›t think the delays were that long — at most, I would say that patients will get scheduled and come back within a few weeks or months.”

What’s more, she discovered through the HPV knowledge questionnaire that many participants did not understand why they were having a follow-up appointment. Anecdotally, some confused HPV with HIV.

“There’s education to be done to inform this target population that those living with HIV are more prone or at increased risk of this virus causing cancer later,” she said. “There are a lot of campaigns around women living with HIV, that they need to do cervical cancer screening. I think we need to really expand this campaign to include that HPV can also cause anal cancer.”

Dr. Wells had planned to primarily investigate the impact of psychosocial factors on wait time to follow-up, but none of those factors were associated with longer wait times.
 

Systems-level factors

That led Ann Gakumo, PhD, chair of nursing at the College of Nursing and Health Sciences of the University of Massachusetts, Boston, to ask what other factors could account for the delay.

There were several, Dr. Wells said. Precarious housing, for example, could have influenced this lag in follow-up. About one in four participants were in transient housing, and one participant reported having been incarcerated. She gathered street addresses and plans to analyze that data to see whether the cases occurred in clusters in specific neighborhoods, as the Yale data indicated.

In addition, the anoscopy clinic was only available to receive patients one day a week and was staffed with only one clinician who was trained to perform HRA. Wait times could stretch for hours. Sometimes, participants had to leave the clinic to attend to other business, and their appointments needed to be rescheduled, Wells said.

In addition to the sometimes poor understanding of the importance of the follow-up test, Dr. Wells said, “we start to see a layering of these barriers. That’s where we start seeing breakdowns. So I’m hoping in a larger study I can address some of these barriers on a multilevel approach.”

This resonated with Dr. Gakumo.

“Oftentimes, we put so much of the responsibility for this on the part of the client and not enough on the part of the provider or on the systems level,” she said.
 

Guiding guidelines

Guidelines on follow-up for abnormal anal Pap test results are scarce, mostly because, unlike cervical cancer, the natural history of HPV-related anal cancers hasn’t been established. The HIV Medical Association does recommend anal Pap tests, but only in cases in which “access to appropriate referral for follow-up, including high-resolution anoscopy, is available.”

In an interview, Cecile Lahiri, MD, assistant professor of infectious disease at Emory University, said that, at Ponce De Leon Center, they recommend an anal Pap for women with HIV who have a history of cervical dysplasia.

There is a reliable association between high-grade abnormal Pap tests and cervical cancer, although low-grade changes can resolve on their own. In the case of anal cancer, especially in patients with HIV, low-grade cell changes are predictive; moreover, for such patients, anal cancer is more likely to recur and is harder to treat, Dr. Lahiri said.

“The cervical environment and the anal environment are very different,” said Dr. Lahiri, who works at the Grady Ponce De Leon Center but was not involved in Dr. Wells’ study. Dr. Lahiri is also a coinvestigator of the multisite, randomized, controlled Anal Cancer HSIL Outcomes Research (ANCHOR) study, which seeks to establish whether early treatment of high-grade anal Pap changes is better than a watch-and-wait approach.

Dr. Lahiri said that when the results of that trial become available, they are more likely to know how important early anoscopy and treatment are. The findings should inform guidelines and insurance coverage of anal Pap tests and anoscopy.

In the meantime, she said, she suspected that, with the ANCHOR trial in 2015, many sites’ capacity for anoscopy may have increased, and the wait times may have gone down.

“One of the most important pieces of the study is actually the time period in which it was conducted,” said Dr. Lahiri, who in 2015 became the clinic’s second physician trained in anoscopy. Currently, more than 200 people at the Ponce De Leon Center are enrolled in the ANCHOR trial. In addition, the general capacity for performing anoscopies has gone up nationwide as a result of the trial, which required that more providers learn how to properly perform an HRA. Many clinicians are not routinely trained in performing HRA, including gastroenterologists and surgeons, Dr. Lahiri said.

“It would be interesting to look at the differences, with the start of ANCHOR being the time point for before and after,” she said.

This article first appeared on Medscape.com.

It took an average of 380 days for people who had received an abnormal anal Pap test result after having been diagnosed with HIV to undergo high-resolution anoscopy (HRA), which is recommended as follow-up.

That delay “revealed missed opportunities for a better experience on the patient, clinic, and provider level,” Jessica Wells, PhD, research assistant professor at the Nell Hodgson Woodruff School of Nursing at Emory University, Atlanta, said in an interview. After all, “a lot can happen in that 1 year,” including early development of human papillomavirus (HPV)–associated anal cancer.

Although it’s too soon to say how significant that delay is with respect to the natural history of anal cancer, Dr. Wells said the data are a potential signal of disparities.

“The findings from my study may foreshadow potential disparities if we don’t have the necessary resources in place to promote follow-up care after an abnormal Pap test, similar to the disparities that we see in cervical cancer,” she said during the virtual Association of Nurses in AIDS Care 2020 Annual Meeting.
 

Single-center study

In the United States, people living with HIV are 19 times more likely to develop anal cancer than the general population, according to a 2018 article in the Journal of Clinical Oncology. Another single-center study from Yale University found that, in minority communities, anal cancer rates were 75% higher than in White communities. Anal cancer rates were 72% higher in communities with greater poverty. As a result, many clinics are beginning to administer Pap tests to determine early signs of HPV infection and associated changes.

In Dr. Wells’ study, which was conducted from 2012 to 2015, 150 adults with HIV who were aged 21 and older were recruited from Grady Ponce De Leon Center in Atlanta. According to a 2018 study from that center, a large minority of participants had late-stage HIV and suppressed immune systems.

All participants had been referred for HRA after a recent abnormal anal Pap test. Participants filled out questionnaires on sociodemographics, internalized HIV-related stigma, depression, risk behaviors, social support, and knowledge about HPV and anal cancer.

Participants were disproportionately older (mean age, 50.9 years); cisgender (86.7%), Black (78%); and gay, lesbian, or bisexual (84.3%). Slightly more than 1 in 10 participants (11.3%) were transgender women.

Although for 6% of participants, Pap test results indicated high-grade squamous intraepithelial lesions (HSIL), an additional 8% had atypical Pap findings that couldn’t exclude HSIL – the kinds of results that are one step away from a cancer diagnosis. More than 80% of participants had low-grade or inconclusive results. Nearly half (44%) of participants’ Pap tests revealed low-grade squamous cell intraepithelial cell lesions (LSIL); 42% indicated atypical squamous cells of undetermined significance.

When Dr. Wells looked at how long participants had waited to undergo HRA, she found something that surprised her: although some participants underwent follow-up assessment in 17 days, for many, it took much longer. The longest wait was 2,350 days – more than 6 years.

“There were quite a few patients who had follow-up beyond 1,000-plus days,” Dr. Wells said in an interview. “I didn›t think the delays were that long — at most, I would say that patients will get scheduled and come back within a few weeks or months.”

What’s more, she discovered through the HPV knowledge questionnaire that many participants did not understand why they were having a follow-up appointment. Anecdotally, some confused HPV with HIV.

“There’s education to be done to inform this target population that those living with HIV are more prone or at increased risk of this virus causing cancer later,” she said. “There are a lot of campaigns around women living with HIV, that they need to do cervical cancer screening. I think we need to really expand this campaign to include that HPV can also cause anal cancer.”

Dr. Wells had planned to primarily investigate the impact of psychosocial factors on wait time to follow-up, but none of those factors were associated with longer wait times.
 

Systems-level factors

That led Ann Gakumo, PhD, chair of nursing at the College of Nursing and Health Sciences of the University of Massachusetts, Boston, to ask what other factors could account for the delay.

There were several, Dr. Wells said. Precarious housing, for example, could have influenced this lag in follow-up. About one in four participants were in transient housing, and one participant reported having been incarcerated. She gathered street addresses and plans to analyze that data to see whether the cases occurred in clusters in specific neighborhoods, as the Yale data indicated.

In addition, the anoscopy clinic was only available to receive patients one day a week and was staffed with only one clinician who was trained to perform HRA. Wait times could stretch for hours. Sometimes, participants had to leave the clinic to attend to other business, and their appointments needed to be rescheduled, Wells said.

In addition to the sometimes poor understanding of the importance of the follow-up test, Dr. Wells said, “we start to see a layering of these barriers. That’s where we start seeing breakdowns. So I’m hoping in a larger study I can address some of these barriers on a multilevel approach.”

This resonated with Dr. Gakumo.

“Oftentimes, we put so much of the responsibility for this on the part of the client and not enough on the part of the provider or on the systems level,” she said.
 

Guiding guidelines

Guidelines on follow-up for abnormal anal Pap test results are scarce, mostly because, unlike cervical cancer, the natural history of HPV-related anal cancers hasn’t been established. The HIV Medical Association does recommend anal Pap tests, but only in cases in which “access to appropriate referral for follow-up, including high-resolution anoscopy, is available.”

In an interview, Cecile Lahiri, MD, assistant professor of infectious disease at Emory University, said that, at Ponce De Leon Center, they recommend an anal Pap for women with HIV who have a history of cervical dysplasia.

There is a reliable association between high-grade abnormal Pap tests and cervical cancer, although low-grade changes can resolve on their own. In the case of anal cancer, especially in patients with HIV, low-grade cell changes are predictive; moreover, for such patients, anal cancer is more likely to recur and is harder to treat, Dr. Lahiri said.

“The cervical environment and the anal environment are very different,” said Dr. Lahiri, who works at the Grady Ponce De Leon Center but was not involved in Dr. Wells’ study. Dr. Lahiri is also a coinvestigator of the multisite, randomized, controlled Anal Cancer HSIL Outcomes Research (ANCHOR) study, which seeks to establish whether early treatment of high-grade anal Pap changes is better than a watch-and-wait approach.

Dr. Lahiri said that when the results of that trial become available, they are more likely to know how important early anoscopy and treatment are. The findings should inform guidelines and insurance coverage of anal Pap tests and anoscopy.

In the meantime, she said, she suspected that, with the ANCHOR trial in 2015, many sites’ capacity for anoscopy may have increased, and the wait times may have gone down.

“One of the most important pieces of the study is actually the time period in which it was conducted,” said Dr. Lahiri, who in 2015 became the clinic’s second physician trained in anoscopy. Currently, more than 200 people at the Ponce De Leon Center are enrolled in the ANCHOR trial. In addition, the general capacity for performing anoscopies has gone up nationwide as a result of the trial, which required that more providers learn how to properly perform an HRA. Many clinicians are not routinely trained in performing HRA, including gastroenterologists and surgeons, Dr. Lahiri said.

“It would be interesting to look at the differences, with the start of ANCHOR being the time point for before and after,” she said.

This article first appeared on Medscape.com.

Same-day HIV pre-exposure prophylaxis (PrEP) prescriptions and insurance navigation services led 70% of people at a Detroit sexually transmitted infection clinic to ask for a PrEP prescription. But only 40% of those same people came back for a follow-up appointment, and 5 acquired HIV during the review period.

To Amanda Allmacher, DNP, RN, nurse practitioner at the Detroit Public Health STD Clinic, that means that same-day PrEP prescribing works and is acceptable. But there’s more work to do on the clinic and pharmacy side to make HIV protection a reality for most of her patients. Allmacher presented her data at the Association of Nurses in AIDS Care 2020 virtual annual meeting.

Dawn K. Smith, MD, epidemiologist and medical officer in the Division of HIV/AIDS Prevention at the Centers for Disease Control and Prevention’s National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, said this adds to other data to show that we’re now entering the next phase of PrEP implementation.

“Our original focus was on uptake — informing folks what PrEP is, why they might benefit from its use, and then prescribing it if accepted,” Smith told Medscape Medical News via email. “Whether standard or same-day [PrEP prescribing], it is clear that uptake is only the first step.”
 

Nurses help navigate

Patients who attended the Detroit Public Health STD Clinic are more likely to be younger, have no insurance, and otherwise “have little to no contact with the healthcare system,” Allmacher said in her presentation. They also tend to come from communities that bear the greatest burden of HIV in the US — in other words, they are often the people most missed in PrEP rollouts thus far.

In response, the clinic implemented a same-day PrEP protocol, in which registered nurses trained in HIV risk assessment identify clients who might most benefit from PrEP. Criteria often include the presence of other STIs. Once the nurse explains what PrEP is and how it works, if the patient is interested, clients meet with a nurse practitioner right then to get the prescription for PrEP. The clinic also does labs to rule out current HIV infection, hepatitis B, metabolic issues, and other STI screening.

But it doesn’t stop there. The clinic used grant funding to offer PrEP navigation and financial counseling services, which help clients navigate the sometimes-thorny process of paying for PrEP. Payment comes either through Medicaid, which in Michigan charges $3 a month for a PrEP prescription, through patient assistance programs, or through private insurance. With clients under age 18 who are interested in PrEP, the clinic works to find a way to access PrEP without having to inform their parents. These same navigators schedule follow-up appointments, offer appointment reminders, and contact clients when they miss an appointment.

“Our navigators and financial counselors are a huge support for our same-day PrEP starts, helping with financial assistance, prior authorization, navigating different plans, and helping patients apply for Medicaid when appropriate,” she said.

The clinic also offers community outreach and incentives, which can include gift cards, bus passes, and pill containers, among other things.

This was a key lesson in setting up the program, Allmacher told Medscape Medical News.

“Starting PrEP at that initial visit allows for clinicians to meet patients where they are and administer care in a more equitable manner,” Allmacher said via email. “Use all available resources and funding sources. We have a versatile team working together to increase access for patients and promote HIV prevention and risk reduction.”
 

Script vs. follow-up

This approach is common, used in places like New York City and San Francisco. So once it was set up Allmacher sat back and waited to see how the program helped clients protect themselves from HIV.

Of the 451 clients eligible for PrEP in 2019, 336 were gay and bisexual men, 6 were transgender women, 61 were heterosexual, cisgender men, and 48 were cisgender women. One transgender man also screened as eligible. Allmacher did not break down data by race.

Uptake was high: 70% of all eligible clients did receive a prescription for PrEP, either generic tenofovir disoproxil fumarate/emtricitabine (Truvada) or tenofovir alafenamide/emtricitabine (Descovy). And uptake was high among people most at risk: 80% of gay and bisexual men who were eligible got a prescription, 60% of eligible cisgender women, 50% of the small number of transgender women, and 32.7% of heterosexual cisgender men did as well. The 1 transgender man also received a prescription.

This is a higher rate than found in a recent PrEP demonstration project, which found that despite gay and bisexual men, transgender adults, and Black people having the highest risk for HIV in the US, state health departments were more likely to refer heterosexual adults for PrEP.

That high uptake rate is encouraging, but follow-up? Not so much. After initial intake, clients are meant to return in a month to double-check their labs, ask about side effects, and start their 90-day supply of the medication. But just 40% showed up for their 30-day appointment, Allmacher said. And only one third of those showed up for the follow-up in 90 days.

By the end of 2019, just 73 of the original 451 clients screened were still taking PrEP.

“It was surprising to see just how significant the follow-up dropped off after that first visit, when the patient initially accepted the prescription,” Allmacher said.

And while it’s possible that some clients get their follow-up care from their primary care providers, “our clinic serves individuals regardless of insurance status and many do not identify having access to primary care for any type of service, PrEP or otherwise,” she said.
 

5 HIV acquisitions

In addition, the program review identified five clients who had been offered PrEP or had taken PrEP briefly who later acquired HIV. Those clients were offered same-day antiretroviral treatment, Allmacher said.

“So we’re finding people who are at high risk for HIV and we can prevent them, but we’re still not quite doing enough,” Allmacher said of those acquisitions. “Clearly we have a lot of work to do to focus on HIV prevention, and we are looking to create a more formal follow-up process” from the clinic’s side.

For instance, clinic staff call clients 1 week after their initial visit to share lab results. “This was identified as a missed opportunity for us to ask about their status, whether they filled their prescription, or if they need further assistance,” she said. “This is an area where our registered nurses are going to be taking on a greater role moving forward.”

Allmacher and team also discovered that, despite PrEP navigators arranging insurance coverage for clients on the day they receive their prescription, sometimes there were still barriers when the client showed up at the pharmacy to pick up their meds. The clinic does not have an in-house pharmacy and does not currently have the funding that would allow them to hand patients a bottle of the appropriate medication when they leave the clinic.

“Navigating the copays and the insurance coverage and using financial assistance through the drug manufacturer — even though we have the support in the clinic, it seems like there’s a disconnect between our clinic and getting to the pharmacy. Not every pharmacy is super familiar with navigating those,” she said. “So we have started to identify some area pharmacies near our clinic that are great at navigating these, and we really try to get our patients to go to places we know can give them assistance.”
 

A version of this story originally appeared on Medscape.com.

Same-day HIV pre-exposure prophylaxis (PrEP) prescriptions and insurance navigation services led 70% of people at a Detroit sexually transmitted infection clinic to ask for a PrEP prescription. But only 40% of those same people came back for a follow-up appointment, and 5 acquired HIV during the review period.

To Amanda Allmacher, DNP, RN, nurse practitioner at the Detroit Public Health STD Clinic, that means that same-day PrEP prescribing works and is acceptable. But there’s more work to do on the clinic and pharmacy side to make HIV protection a reality for most of her patients. Allmacher presented her data at the Association of Nurses in AIDS Care 2020 virtual annual meeting.

Dawn K. Smith, MD, epidemiologist and medical officer in the Division of HIV/AIDS Prevention at the Centers for Disease Control and Prevention’s National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, said this adds to other data to show that we’re now entering the next phase of PrEP implementation.

“Our original focus was on uptake — informing folks what PrEP is, why they might benefit from its use, and then prescribing it if accepted,” Smith told Medscape Medical News via email. “Whether standard or same-day [PrEP prescribing], it is clear that uptake is only the first step.”
 

Nurses help navigate

Patients who attended the Detroit Public Health STD Clinic are more likely to be younger, have no insurance, and otherwise “have little to no contact with the healthcare system,” Allmacher said in her presentation. They also tend to come from communities that bear the greatest burden of HIV in the US — in other words, they are often the people most missed in PrEP rollouts thus far.

In response, the clinic implemented a same-day PrEP protocol, in which registered nurses trained in HIV risk assessment identify clients who might most benefit from PrEP. Criteria often include the presence of other STIs. Once the nurse explains what PrEP is and how it works, if the patient is interested, clients meet with a nurse practitioner right then to get the prescription for PrEP. The clinic also does labs to rule out current HIV infection, hepatitis B, metabolic issues, and other STI screening.

But it doesn’t stop there. The clinic used grant funding to offer PrEP navigation and financial counseling services, which help clients navigate the sometimes-thorny process of paying for PrEP. Payment comes either through Medicaid, which in Michigan charges $3 a month for a PrEP prescription, through patient assistance programs, or through private insurance. With clients under age 18 who are interested in PrEP, the clinic works to find a way to access PrEP without having to inform their parents. These same navigators schedule follow-up appointments, offer appointment reminders, and contact clients when they miss an appointment.

“Our navigators and financial counselors are a huge support for our same-day PrEP starts, helping with financial assistance, prior authorization, navigating different plans, and helping patients apply for Medicaid when appropriate,” she said.

The clinic also offers community outreach and incentives, which can include gift cards, bus passes, and pill containers, among other things.

This was a key lesson in setting up the program, Allmacher told Medscape Medical News.

“Starting PrEP at that initial visit allows for clinicians to meet patients where they are and administer care in a more equitable manner,” Allmacher said via email. “Use all available resources and funding sources. We have a versatile team working together to increase access for patients and promote HIV prevention and risk reduction.”
 

Script vs. follow-up

This approach is common, used in places like New York City and San Francisco. So once it was set up Allmacher sat back and waited to see how the program helped clients protect themselves from HIV.

Of the 451 clients eligible for PrEP in 2019, 336 were gay and bisexual men, 6 were transgender women, 61 were heterosexual, cisgender men, and 48 were cisgender women. One transgender man also screened as eligible. Allmacher did not break down data by race.

Uptake was high: 70% of all eligible clients did receive a prescription for PrEP, either generic tenofovir disoproxil fumarate/emtricitabine (Truvada) or tenofovir alafenamide/emtricitabine (Descovy). And uptake was high among people most at risk: 80% of gay and bisexual men who were eligible got a prescription, 60% of eligible cisgender women, 50% of the small number of transgender women, and 32.7% of heterosexual cisgender men did as well. The 1 transgender man also received a prescription.

This is a higher rate than found in a recent PrEP demonstration project, which found that despite gay and bisexual men, transgender adults, and Black people having the highest risk for HIV in the US, state health departments were more likely to refer heterosexual adults for PrEP.

That high uptake rate is encouraging, but follow-up? Not so much. After initial intake, clients are meant to return in a month to double-check their labs, ask about side effects, and start their 90-day supply of the medication. But just 40% showed up for their 30-day appointment, Allmacher said. And only one third of those showed up for the follow-up in 90 days.

By the end of 2019, just 73 of the original 451 clients screened were still taking PrEP.

“It was surprising to see just how significant the follow-up dropped off after that first visit, when the patient initially accepted the prescription,” Allmacher said.

And while it’s possible that some clients get their follow-up care from their primary care providers, “our clinic serves individuals regardless of insurance status and many do not identify having access to primary care for any type of service, PrEP or otherwise,” she said.
 

5 HIV acquisitions

In addition, the program review identified five clients who had been offered PrEP or had taken PrEP briefly who later acquired HIV. Those clients were offered same-day antiretroviral treatment, Allmacher said.

“So we’re finding people who are at high risk for HIV and we can prevent them, but we’re still not quite doing enough,” Allmacher said of those acquisitions. “Clearly we have a lot of work to do to focus on HIV prevention, and we are looking to create a more formal follow-up process” from the clinic’s side.

For instance, clinic staff call clients 1 week after their initial visit to share lab results. “This was identified as a missed opportunity for us to ask about their status, whether they filled their prescription, or if they need further assistance,” she said. “This is an area where our registered nurses are going to be taking on a greater role moving forward.”

Allmacher and team also discovered that, despite PrEP navigators arranging insurance coverage for clients on the day they receive their prescription, sometimes there were still barriers when the client showed up at the pharmacy to pick up their meds. The clinic does not have an in-house pharmacy and does not currently have the funding that would allow them to hand patients a bottle of the appropriate medication when they leave the clinic.

“Navigating the copays and the insurance coverage and using financial assistance through the drug manufacturer — even though we have the support in the clinic, it seems like there’s a disconnect between our clinic and getting to the pharmacy. Not every pharmacy is super familiar with navigating those,” she said. “So we have started to identify some area pharmacies near our clinic that are great at navigating these, and we really try to get our patients to go to places we know can give them assistance.”
 

A version of this story originally appeared on Medscape.com.

Same-day HIV pre-exposure prophylaxis (PrEP) prescriptions and insurance navigation services led 70% of people at a Detroit sexually transmitted infection clinic to ask for a PrEP prescription. But only 40% of those same people came back for a follow-up appointment, and 5 acquired HIV during the review period.

To Amanda Allmacher, DNP, RN, nurse practitioner at the Detroit Public Health STD Clinic, that means that same-day PrEP prescribing works and is acceptable. But there’s more work to do on the clinic and pharmacy side to make HIV protection a reality for most of her patients. Allmacher presented her data at the Association of Nurses in AIDS Care 2020 virtual annual meeting.

Dawn K. Smith, MD, epidemiologist and medical officer in the Division of HIV/AIDS Prevention at the Centers for Disease Control and Prevention’s National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, said this adds to other data to show that we’re now entering the next phase of PrEP implementation.

“Our original focus was on uptake — informing folks what PrEP is, why they might benefit from its use, and then prescribing it if accepted,” Smith told Medscape Medical News via email. “Whether standard or same-day [PrEP prescribing], it is clear that uptake is only the first step.”
 

Nurses help navigate

Patients who attended the Detroit Public Health STD Clinic are more likely to be younger, have no insurance, and otherwise “have little to no contact with the healthcare system,” Allmacher said in her presentation. They also tend to come from communities that bear the greatest burden of HIV in the US — in other words, they are often the people most missed in PrEP rollouts thus far.

In response, the clinic implemented a same-day PrEP protocol, in which registered nurses trained in HIV risk assessment identify clients who might most benefit from PrEP. Criteria often include the presence of other STIs. Once the nurse explains what PrEP is and how it works, if the patient is interested, clients meet with a nurse practitioner right then to get the prescription for PrEP. The clinic also does labs to rule out current HIV infection, hepatitis B, metabolic issues, and other STI screening.

But it doesn’t stop there. The clinic used grant funding to offer PrEP navigation and financial counseling services, which help clients navigate the sometimes-thorny process of paying for PrEP. Payment comes either through Medicaid, which in Michigan charges $3 a month for a PrEP prescription, through patient assistance programs, or through private insurance. With clients under age 18 who are interested in PrEP, the clinic works to find a way to access PrEP without having to inform their parents. These same navigators schedule follow-up appointments, offer appointment reminders, and contact clients when they miss an appointment.

“Our navigators and financial counselors are a huge support for our same-day PrEP starts, helping with financial assistance, prior authorization, navigating different plans, and helping patients apply for Medicaid when appropriate,” she said.

The clinic also offers community outreach and incentives, which can include gift cards, bus passes, and pill containers, among other things.

This was a key lesson in setting up the program, Allmacher told Medscape Medical News.

“Starting PrEP at that initial visit allows for clinicians to meet patients where they are and administer care in a more equitable manner,” Allmacher said via email. “Use all available resources and funding sources. We have a versatile team working together to increase access for patients and promote HIV prevention and risk reduction.”
 

Script vs. follow-up

This approach is common, used in places like New York City and San Francisco. So once it was set up Allmacher sat back and waited to see how the program helped clients protect themselves from HIV.

Of the 451 clients eligible for PrEP in 2019, 336 were gay and bisexual men, 6 were transgender women, 61 were heterosexual, cisgender men, and 48 were cisgender women. One transgender man also screened as eligible. Allmacher did not break down data by race.

Uptake was high: 70% of all eligible clients did receive a prescription for PrEP, either generic tenofovir disoproxil fumarate/emtricitabine (Truvada) or tenofovir alafenamide/emtricitabine (Descovy). And uptake was high among people most at risk: 80% of gay and bisexual men who were eligible got a prescription, 60% of eligible cisgender women, 50% of the small number of transgender women, and 32.7% of heterosexual cisgender men did as well. The 1 transgender man also received a prescription.

This is a higher rate than found in a recent PrEP demonstration project, which found that despite gay and bisexual men, transgender adults, and Black people having the highest risk for HIV in the US, state health departments were more likely to refer heterosexual adults for PrEP.

That high uptake rate is encouraging, but follow-up? Not so much. After initial intake, clients are meant to return in a month to double-check their labs, ask about side effects, and start their 90-day supply of the medication. But just 40% showed up for their 30-day appointment, Allmacher said. And only one third of those showed up for the follow-up in 90 days.

By the end of 2019, just 73 of the original 451 clients screened were still taking PrEP.

“It was surprising to see just how significant the follow-up dropped off after that first visit, when the patient initially accepted the prescription,” Allmacher said.

And while it’s possible that some clients get their follow-up care from their primary care providers, “our clinic serves individuals regardless of insurance status and many do not identify having access to primary care for any type of service, PrEP or otherwise,” she said.
 

5 HIV acquisitions

In addition, the program review identified five clients who had been offered PrEP or had taken PrEP briefly who later acquired HIV. Those clients were offered same-day antiretroviral treatment, Allmacher said.

“So we’re finding people who are at high risk for HIV and we can prevent them, but we’re still not quite doing enough,” Allmacher said of those acquisitions. “Clearly we have a lot of work to do to focus on HIV prevention, and we are looking to create a more formal follow-up process” from the clinic’s side.

For instance, clinic staff call clients 1 week after their initial visit to share lab results. “This was identified as a missed opportunity for us to ask about their status, whether they filled their prescription, or if they need further assistance,” she said. “This is an area where our registered nurses are going to be taking on a greater role moving forward.”

Allmacher and team also discovered that, despite PrEP navigators arranging insurance coverage for clients on the day they receive their prescription, sometimes there were still barriers when the client showed up at the pharmacy to pick up their meds. The clinic does not have an in-house pharmacy and does not currently have the funding that would allow them to hand patients a bottle of the appropriate medication when they leave the clinic.

“Navigating the copays and the insurance coverage and using financial assistance through the drug manufacturer — even though we have the support in the clinic, it seems like there’s a disconnect between our clinic and getting to the pharmacy. Not every pharmacy is super familiar with navigating those,” she said. “So we have started to identify some area pharmacies near our clinic that are great at navigating these, and we really try to get our patients to go to places we know can give them assistance.”
 

A version of this story originally appeared on Medscape.com.

The FDA issued an emergency use authorization Tuesday for the first self-testing COVID-19 kit to use at home, which provides results in about 30 minutes.

The Lucira COVID-19 All-In-One Test-Kit is a single-use test that has a nasal swab to collect samples for people ages 14 and older. It’s available only by prescription, which can be given by a doctor who suspects a patient may have contracted the coronavirus.

“While COVID-19 diagnostic tests have been authorized for at-home collection, this is the first that can be fully self-administered and provide results at home,” FDA Commissioner Stephen Hahn, MD, said in the statement.

The test kit can also be used in doctor’s offices, hospitals, urgent care centers, and emergency rooms for all ages, but samples must be collected by a health care professional if the patient is under age 14.

After using the nasal swab, the test works by swirling the sample in a vial and then placing it in the provided test unit, according to the FDA. Within 30 minutes, the results appear on the unit’s light-up display. People who receive a positive result should self-isolate and seek care from their doctor. Those who test negative but have COVID-like symptoms should follow up with their doctor, since a negative result doesn’t necessarily mean they don’t have the coronavirus.

Testing is still a key part of controlling the spread of the coronavirus, Reuters reports. The United States surpassed 11 million infections Sunday, only 8 days after passing 10 million cases.

With the at-home testing kit, public health officials still need to track and monitor results. As part of the emergency use authorization, the FDA requires doctors who prescribe the tests to report all results to public health authorities based on local, state, and federal requirements. Lucira Health, the test maker, also created box labeling and instructions to help doctors to report results.

“Now, more Americans who may have COVID-19 will be able to take immediate action, based on their results, to protect themselves and those around them,” Jeff Shuren, MD, director of the FDA’s Center for Devices and Radiological Health, said in the statement.

This article first appeared on WebMD.com.

The FDA issued an emergency use authorization Tuesday for the first self-testing COVID-19 kit to use at home, which provides results in about 30 minutes.

The Lucira COVID-19 All-In-One Test-Kit is a single-use test that has a nasal swab to collect samples for people ages 14 and older. It’s available only by prescription, which can be given by a doctor who suspects a patient may have contracted the coronavirus.

“While COVID-19 diagnostic tests have been authorized for at-home collection, this is the first that can be fully self-administered and provide results at home,” FDA Commissioner Stephen Hahn, MD, said in the statement.

The test kit can also be used in doctor’s offices, hospitals, urgent care centers, and emergency rooms for all ages, but samples must be collected by a health care professional if the patient is under age 14.

After using the nasal swab, the test works by swirling the sample in a vial and then placing it in the provided test unit, according to the FDA. Within 30 minutes, the results appear on the unit’s light-up display. People who receive a positive result should self-isolate and seek care from their doctor. Those who test negative but have COVID-like symptoms should follow up with their doctor, since a negative result doesn’t necessarily mean they don’t have the coronavirus.

Testing is still a key part of controlling the spread of the coronavirus, Reuters reports. The United States surpassed 11 million infections Sunday, only 8 days after passing 10 million cases.

With the at-home testing kit, public health officials still need to track and monitor results. As part of the emergency use authorization, the FDA requires doctors who prescribe the tests to report all results to public health authorities based on local, state, and federal requirements. Lucira Health, the test maker, also created box labeling and instructions to help doctors to report results.

“Now, more Americans who may have COVID-19 will be able to take immediate action, based on their results, to protect themselves and those around them,” Jeff Shuren, MD, director of the FDA’s Center for Devices and Radiological Health, said in the statement.

This article first appeared on WebMD.com.

The FDA issued an emergency use authorization Tuesday for the first self-testing COVID-19 kit to use at home, which provides results in about 30 minutes.

The Lucira COVID-19 All-In-One Test-Kit is a single-use test that has a nasal swab to collect samples for people ages 14 and older. It’s available only by prescription, which can be given by a doctor who suspects a patient may have contracted the coronavirus.

“While COVID-19 diagnostic tests have been authorized for at-home collection, this is the first that can be fully self-administered and provide results at home,” FDA Commissioner Stephen Hahn, MD, said in the statement.

The test kit can also be used in doctor’s offices, hospitals, urgent care centers, and emergency rooms for all ages, but samples must be collected by a health care professional if the patient is under age 14.

After using the nasal swab, the test works by swirling the sample in a vial and then placing it in the provided test unit, according to the FDA. Within 30 minutes, the results appear on the unit’s light-up display. People who receive a positive result should self-isolate and seek care from their doctor. Those who test negative but have COVID-like symptoms should follow up with their doctor, since a negative result doesn’t necessarily mean they don’t have the coronavirus.

Testing is still a key part of controlling the spread of the coronavirus, Reuters reports. The United States surpassed 11 million infections Sunday, only 8 days after passing 10 million cases.

With the at-home testing kit, public health officials still need to track and monitor results. As part of the emergency use authorization, the FDA requires doctors who prescribe the tests to report all results to public health authorities based on local, state, and federal requirements. Lucira Health, the test maker, also created box labeling and instructions to help doctors to report results.

“Now, more Americans who may have COVID-19 will be able to take immediate action, based on their results, to protect themselves and those around them,” Jeff Shuren, MD, director of the FDA’s Center for Devices and Radiological Health, said in the statement.

This article first appeared on WebMD.com.

Researchers are testing whether a probiotic called Lactobacillus rhamnosus GG can prevent COVID-19 in household contacts of COVID patients.

On the Nov. 12 episode of the Blood & Cancer podcast, Anthony D. Sung, MD, of Duke University, Durham, N.C., joined host David H. Henry, MD, of Penn Medicine in Philadelphia, to discuss the trial of LGG as well as other research. The following transcript of that discussion has been edited for length and clarity.
 

David Henry, MD: Here we are in COVID. We’re recording this the first week in November. Sadly, cases are spiking in the country. And I understand you’ve got some information that you might share about how manipulating ... the microbiome that we all exist with inside our gut might somehow play into doing better or worse with COVID.

Anthony Sung, MD: Absolutely. So, as associate director of the Duke Microbiome Center, I was approached by one of my colleagues, Paul Wischmeyer, who is a professor of anesthesiology and critical care medicine at Duke. Paul had previously done some very nice murine studies with the probiotic Lactobacillus rhamnosus GG, or LGG.

He showed, in a murine model of pseudomonas pneumonia, that giving LGG to mice would help modulate their microbiome and, in turn, their immune system, leading to decreased inflammation, decreased TNF-alpha, IL [interleukin]-2, and IL-6, [and] increased Treg cells [Clin Nutr. 2017;36[6]:1549-57]. This also helped prevent lung injury, and it actually significantly improved survival in mice receiving LGG [Shock. 2013;40[6]:496-503].

In addition, there has been a randomized clinical trial of LGG showing that its administration would help prevent ventilator-associated pneumonia, or VAP [Am J Respir Crit Care Med. 2010 Oct 15;182[8]:1058-64].

And a few years ago, there was another RCT [randomized, controlled trial], published in Nature, showing that another Lactobacillus product significantly decreased the combined endpoint of sepsis and mortality, primarily by reducing lower respiratory tract infection [Nature. 2017 Aug 24;548[7668]:407-12].
 

Dr. Henry: And how is that working? What is the bacillus doing to help us?

Dr. Sung: We think it’s through modulating the immune system. As mentioned in Paul’s studies, we saw significantly decreased amounts of TNF-alpha, IL-2, and IL-6, which are the same cytokines that have been implicated in COVID-19 and associated with increased lung injury in patients during this pandemic.

And we believe that by giving individuals this probiotic, LGG, we may help modulate the immune system, decrease lung injury and symptoms, and maybe even prevent COVID-19.

So with support from the Duke Microbiome Center, as well as private donations and philanthropy, we are conducting a randomized clinical trial of LGG to prevent COVID-19 in household contacts who’ve been exposed to the disease. In other words, if someone in the house gets COVID-19, we want to try to prophylax everybody else living in that house and prevent them from coming down with the same infection.
 

Dr. Henry: And this is an oral administration?

Dr. Sung: Correct. This is an oral pill, two pills once a day.

Dr. Henry: And it’s an ongoing study, of course, in COVID right now?

Dr. Sung: Correct. So we have an IND [investigational new drug application] from the FDA [Food and Drug Administration], and we are actively recruiting subjects both at Duke University, but also due to the unique study design, we can enroll patients anywhere across the country. Because of the importance of social distancing, everything is done remotely.

So a household contact can hear about us, either through your podcast or one of our Facebook ads or through other media. They can reach out to our study website, which is https://sites.duke.edu/protectehc, or reach out to us at our study email, protect-ehc@duke.edu.

And we can go ahead and screen them for eligibility in our trial. And if they are eligible and they consent to participate, we will mail them a package basically overnight, FedEx, containing either LGG or placebo, as well as kits so that they can self-collect their stool and nasal swabs so we can test it for SARS-CoV-2 by PCR [polymerase chain reaction] and look at the microbiome.

Dr. Sung and Dr. Henry have no relevant disclosures. Funding for the trial is provided by the Duke Microbiome Center and philanthropic giving. The LGG and placebo used in the trial are provided by DSM.

Researchers are testing whether a probiotic called Lactobacillus rhamnosus GG can prevent COVID-19 in household contacts of COVID patients.

On the Nov. 12 episode of the Blood & Cancer podcast, Anthony D. Sung, MD, of Duke University, Durham, N.C., joined host David H. Henry, MD, of Penn Medicine in Philadelphia, to discuss the trial of LGG as well as other research. The following transcript of that discussion has been edited for length and clarity.
 

David Henry, MD: Here we are in COVID. We’re recording this the first week in November. Sadly, cases are spiking in the country. And I understand you’ve got some information that you might share about how manipulating ... the microbiome that we all exist with inside our gut might somehow play into doing better or worse with COVID.

Anthony Sung, MD: Absolutely. So, as associate director of the Duke Microbiome Center, I was approached by one of my colleagues, Paul Wischmeyer, who is a professor of anesthesiology and critical care medicine at Duke. Paul had previously done some very nice murine studies with the probiotic Lactobacillus rhamnosus GG, or LGG.

He showed, in a murine model of pseudomonas pneumonia, that giving LGG to mice would help modulate their microbiome and, in turn, their immune system, leading to decreased inflammation, decreased TNF-alpha, IL [interleukin]-2, and IL-6, [and] increased Treg cells [Clin Nutr. 2017;36[6]:1549-57]. This also helped prevent lung injury, and it actually significantly improved survival in mice receiving LGG [Shock. 2013;40[6]:496-503].

In addition, there has been a randomized clinical trial of LGG showing that its administration would help prevent ventilator-associated pneumonia, or VAP [Am J Respir Crit Care Med. 2010 Oct 15;182[8]:1058-64].

And a few years ago, there was another RCT [randomized, controlled trial], published in Nature, showing that another Lactobacillus product significantly decreased the combined endpoint of sepsis and mortality, primarily by reducing lower respiratory tract infection [Nature. 2017 Aug 24;548[7668]:407-12].
 

Dr. Henry: And how is that working? What is the bacillus doing to help us?

Dr. Sung: We think it’s through modulating the immune system. As mentioned in Paul’s studies, we saw significantly decreased amounts of TNF-alpha, IL-2, and IL-6, which are the same cytokines that have been implicated in COVID-19 and associated with increased lung injury in patients during this pandemic.

And we believe that by giving individuals this probiotic, LGG, we may help modulate the immune system, decrease lung injury and symptoms, and maybe even prevent COVID-19.

So with support from the Duke Microbiome Center, as well as private donations and philanthropy, we are conducting a randomized clinical trial of LGG to prevent COVID-19 in household contacts who’ve been exposed to the disease. In other words, if someone in the house gets COVID-19, we want to try to prophylax everybody else living in that house and prevent them from coming down with the same infection.
 

Dr. Henry: And this is an oral administration?

Dr. Sung: Correct. This is an oral pill, two pills once a day.

Dr. Henry: And it’s an ongoing study, of course, in COVID right now?

Dr. Sung: Correct. So we have an IND [investigational new drug application] from the FDA [Food and Drug Administration], and we are actively recruiting subjects both at Duke University, but also due to the unique study design, we can enroll patients anywhere across the country. Because of the importance of social distancing, everything is done remotely.

So a household contact can hear about us, either through your podcast or one of our Facebook ads or through other media. They can reach out to our study website, which is https://sites.duke.edu/protectehc, or reach out to us at our study email, protect-ehc@duke.edu.

And we can go ahead and screen them for eligibility in our trial. And if they are eligible and they consent to participate, we will mail them a package basically overnight, FedEx, containing either LGG or placebo, as well as kits so that they can self-collect their stool and nasal swabs so we can test it for SARS-CoV-2 by PCR [polymerase chain reaction] and look at the microbiome.

Dr. Sung and Dr. Henry have no relevant disclosures. Funding for the trial is provided by the Duke Microbiome Center and philanthropic giving. The LGG and placebo used in the trial are provided by DSM.

Researchers are testing whether a probiotic called Lactobacillus rhamnosus GG can prevent COVID-19 in household contacts of COVID patients.

On the Nov. 12 episode of the Blood & Cancer podcast, Anthony D. Sung, MD, of Duke University, Durham, N.C., joined host David H. Henry, MD, of Penn Medicine in Philadelphia, to discuss the trial of LGG as well as other research. The following transcript of that discussion has been edited for length and clarity.
 

David Henry, MD: Here we are in COVID. We’re recording this the first week in November. Sadly, cases are spiking in the country. And I understand you’ve got some information that you might share about how manipulating ... the microbiome that we all exist with inside our gut might somehow play into doing better or worse with COVID.

Anthony Sung, MD: Absolutely. So, as associate director of the Duke Microbiome Center, I was approached by one of my colleagues, Paul Wischmeyer, who is a professor of anesthesiology and critical care medicine at Duke. Paul had previously done some very nice murine studies with the probiotic Lactobacillus rhamnosus GG, or LGG.

He showed, in a murine model of pseudomonas pneumonia, that giving LGG to mice would help modulate their microbiome and, in turn, their immune system, leading to decreased inflammation, decreased TNF-alpha, IL [interleukin]-2, and IL-6, [and] increased Treg cells [Clin Nutr. 2017;36[6]:1549-57]. This also helped prevent lung injury, and it actually significantly improved survival in mice receiving LGG [Shock. 2013;40[6]:496-503].

In addition, there has been a randomized clinical trial of LGG showing that its administration would help prevent ventilator-associated pneumonia, or VAP [Am J Respir Crit Care Med. 2010 Oct 15;182[8]:1058-64].

And a few years ago, there was another RCT [randomized, controlled trial], published in Nature, showing that another Lactobacillus product significantly decreased the combined endpoint of sepsis and mortality, primarily by reducing lower respiratory tract infection [Nature. 2017 Aug 24;548[7668]:407-12].
 

Dr. Henry: And how is that working? What is the bacillus doing to help us?

Dr. Sung: We think it’s through modulating the immune system. As mentioned in Paul’s studies, we saw significantly decreased amounts of TNF-alpha, IL-2, and IL-6, which are the same cytokines that have been implicated in COVID-19 and associated with increased lung injury in patients during this pandemic.

And we believe that by giving individuals this probiotic, LGG, we may help modulate the immune system, decrease lung injury and symptoms, and maybe even prevent COVID-19.

So with support from the Duke Microbiome Center, as well as private donations and philanthropy, we are conducting a randomized clinical trial of LGG to prevent COVID-19 in household contacts who’ve been exposed to the disease. In other words, if someone in the house gets COVID-19, we want to try to prophylax everybody else living in that house and prevent them from coming down with the same infection.
 

Dr. Henry: And this is an oral administration?

Dr. Sung: Correct. This is an oral pill, two pills once a day.

Dr. Henry: And it’s an ongoing study, of course, in COVID right now?

Dr. Sung: Correct. So we have an IND [investigational new drug application] from the FDA [Food and Drug Administration], and we are actively recruiting subjects both at Duke University, but also due to the unique study design, we can enroll patients anywhere across the country. Because of the importance of social distancing, everything is done remotely.

So a household contact can hear about us, either through your podcast or one of our Facebook ads or through other media. They can reach out to our study website, which is https://sites.duke.edu/protectehc, or reach out to us at our study email, protect-ehc@duke.edu.

And we can go ahead and screen them for eligibility in our trial. And if they are eligible and they consent to participate, we will mail them a package basically overnight, FedEx, containing either LGG or placebo, as well as kits so that they can self-collect their stool and nasal swabs so we can test it for SARS-CoV-2 by PCR [polymerase chain reaction] and look at the microbiome.

Dr. Sung and Dr. Henry have no relevant disclosures. Funding for the trial is provided by the Duke Microbiome Center and philanthropic giving. The LGG and placebo used in the trial are provided by DSM.

After initial promising interim results on Nov. 9, Pfizer and BioNTech today announced that their mRNA vaccine, in development to prevent COVID-19, is 95% effective.

Final analysis of the randomized, phase 3 study of more than 43,000 people yielded 170 confirmed cases of COVID-19 – with 162 positive cases in the placebo group versus 8 in the BNT162b2 vaccine group.

Researchers reported 10 severe cases of COVID-19 in the trial, 9 of which occurred in the placebo group.

The study was ethnically diverse, and results were consistent across gender and age groups, with a 94% efficacy reported among participants aged older than 65 years.

Pfizer plans to file for an emergency-use authorization with the Food and Drug Administration “within days,” having now met all the FDA data endpoints, according to a news release from the two companies.

The vaccine was well tolerated with no serious safety concerns, the company stated. Two grade 3 adverse events were reported – fatigue in 3.8% of participants and headache in 2%.

The 95% efficacy places the Pfizer vaccine in the same neighborhood as the interim results of the Moderna vaccine, reported at 94.5%. Both products are two-dose mRNA vaccines.

As of Nov. 13, of 43,661 total participants in the Pfizer vaccine phase 3 trial, 41,135 received a second dose. The final results are based on two outcomes measured 7 days after the second dose: vaccine efficacy in people without prior SARS-CoV-2 infection as well as a secondary outcome in people both with and without prior SARS-CoV-2 infection.

The 95% vaccine efficacy was statistically significant, compared with placebo (P < .0001).
 

‘Historic 8-month journey’

The BNT162b2 vaccine candidate is a joint effort between Pfizer and BioNTech. “The study results mark an important step in this historic 8-month journey to bring forward a vaccine capable of helping to end this devastating pandemic,” Albert Bourla, DVM, PhD, Pfizer chairman and CEO, said in a statement. “With hundreds of thousands of people around the globe infected every day, we urgently need to get a safe and effective vaccine to the world.”

Ugur Sahin, MD, PhD, cofounder and CEO of BioNTech, added, “we are grateful that the first global trial to reach the final efficacy analysis mark indicates that a high rate of protection against COVID-19 can be achieved very fast after the first 30-mcg dose, underscoring the power of BNT162 in providing early protection.”

The two companies expect to produce up to 50 million vaccine doses in 2020 for global distribution. Projections for 2021 include up to 1.3 billion doses.

The companies also designed temperature-controlled thermal shipping containers with dry ice to maintain the required, approximate –70° C (–94° F) conditions. Clinicians can use the containers as temporary storage units for up to 15 days by replacing the dry ice.

This article first appeared on Medscape.com.

After initial promising interim results on Nov. 9, Pfizer and BioNTech today announced that their mRNA vaccine, in development to prevent COVID-19, is 95% effective.

Final analysis of the randomized, phase 3 study of more than 43,000 people yielded 170 confirmed cases of COVID-19 – with 162 positive cases in the placebo group versus 8 in the BNT162b2 vaccine group.

Researchers reported 10 severe cases of COVID-19 in the trial, 9 of which occurred in the placebo group.

The study was ethnically diverse, and results were consistent across gender and age groups, with a 94% efficacy reported among participants aged older than 65 years.

Pfizer plans to file for an emergency-use authorization with the Food and Drug Administration “within days,” having now met all the FDA data endpoints, according to a news release from the two companies.

The vaccine was well tolerated with no serious safety concerns, the company stated. Two grade 3 adverse events were reported – fatigue in 3.8% of participants and headache in 2%.

The 95% efficacy places the Pfizer vaccine in the same neighborhood as the interim results of the Moderna vaccine, reported at 94.5%. Both products are two-dose mRNA vaccines.

As of Nov. 13, of 43,661 total participants in the Pfizer vaccine phase 3 trial, 41,135 received a second dose. The final results are based on two outcomes measured 7 days after the second dose: vaccine efficacy in people without prior SARS-CoV-2 infection as well as a secondary outcome in people both with and without prior SARS-CoV-2 infection.

The 95% vaccine efficacy was statistically significant, compared with placebo (P < .0001).
 

‘Historic 8-month journey’

The BNT162b2 vaccine candidate is a joint effort between Pfizer and BioNTech. “The study results mark an important step in this historic 8-month journey to bring forward a vaccine capable of helping to end this devastating pandemic,” Albert Bourla, DVM, PhD, Pfizer chairman and CEO, said in a statement. “With hundreds of thousands of people around the globe infected every day, we urgently need to get a safe and effective vaccine to the world.”

Ugur Sahin, MD, PhD, cofounder and CEO of BioNTech, added, “we are grateful that the first global trial to reach the final efficacy analysis mark indicates that a high rate of protection against COVID-19 can be achieved very fast after the first 30-mcg dose, underscoring the power of BNT162 in providing early protection.”

The two companies expect to produce up to 50 million vaccine doses in 2020 for global distribution. Projections for 2021 include up to 1.3 billion doses.

The companies also designed temperature-controlled thermal shipping containers with dry ice to maintain the required, approximate –70° C (–94° F) conditions. Clinicians can use the containers as temporary storage units for up to 15 days by replacing the dry ice.

This article first appeared on Medscape.com.

After initial promising interim results on Nov. 9, Pfizer and BioNTech today announced that their mRNA vaccine, in development to prevent COVID-19, is 95% effective.

Final analysis of the randomized, phase 3 study of more than 43,000 people yielded 170 confirmed cases of COVID-19 – with 162 positive cases in the placebo group versus 8 in the BNT162b2 vaccine group.

Researchers reported 10 severe cases of COVID-19 in the trial, 9 of which occurred in the placebo group.

The study was ethnically diverse, and results were consistent across gender and age groups, with a 94% efficacy reported among participants aged older than 65 years.

Pfizer plans to file for an emergency-use authorization with the Food and Drug Administration “within days,” having now met all the FDA data endpoints, according to a news release from the two companies.

The vaccine was well tolerated with no serious safety concerns, the company stated. Two grade 3 adverse events were reported – fatigue in 3.8% of participants and headache in 2%.

The 95% efficacy places the Pfizer vaccine in the same neighborhood as the interim results of the Moderna vaccine, reported at 94.5%. Both products are two-dose mRNA vaccines.

As of Nov. 13, of 43,661 total participants in the Pfizer vaccine phase 3 trial, 41,135 received a second dose. The final results are based on two outcomes measured 7 days after the second dose: vaccine efficacy in people without prior SARS-CoV-2 infection as well as a secondary outcome in people both with and without prior SARS-CoV-2 infection.

The 95% vaccine efficacy was statistically significant, compared with placebo (P < .0001).
 

‘Historic 8-month journey’

The BNT162b2 vaccine candidate is a joint effort between Pfizer and BioNTech. “The study results mark an important step in this historic 8-month journey to bring forward a vaccine capable of helping to end this devastating pandemic,” Albert Bourla, DVM, PhD, Pfizer chairman and CEO, said in a statement. “With hundreds of thousands of people around the globe infected every day, we urgently need to get a safe and effective vaccine to the world.”

Ugur Sahin, MD, PhD, cofounder and CEO of BioNTech, added, “we are grateful that the first global trial to reach the final efficacy analysis mark indicates that a high rate of protection against COVID-19 can be achieved very fast after the first 30-mcg dose, underscoring the power of BNT162 in providing early protection.”

The two companies expect to produce up to 50 million vaccine doses in 2020 for global distribution. Projections for 2021 include up to 1.3 billion doses.

The companies also designed temperature-controlled thermal shipping containers with dry ice to maintain the required, approximate –70° C (–94° F) conditions. Clinicians can use the containers as temporary storage units for up to 15 days by replacing the dry ice.

This article first appeared on Medscape.com.