CROI 2018

 

BOSTON – A lot of people do well with HIV thanks to potent antiretrovirals, but there’s still at least one group that needs extra attention: HIV patients with chronic kidney disease (CKD), according to Lene Ryom, MD, PhD, an HIV researcher at the University of Copenhagen.

She was the lead investigator on a review of 2,467 HIV patients with CKD – which is becoming more common in HIV as patients live longer – and 33,427 HIV patients without CKD.

decade3d/Thinkstock

At a median of 2.7 years after CKD diagnosis, 595 (24.1%) developed a serious clinical event, defined in the study as end-stage renal disease, end-stage liver disease, cardiovascular disease, malignancy, other AIDS events, or death. Almost 8% of patients developed a serious clinical event within a year of CKD diagnosis. Smoking, diabetes, dyslipidemia, body mass index below 18 kg/m², and poor HIV control were identified as modifiable risk factors.

The incidence of serious clinical events following CKD diagnosis was 68.9 events per 1,000 patient-years. Among the HIV patients without CKD, the incidence was 23 events per 1,000 patient-years.

“In an era when many HIV patients require much less management due to effective antiretroviral treatment, those living with CKD have a much higher burden of serious clinical events and require much closer monitoring. Modifiable risk factors ... play a central role in CKD morbidity and mortality, highlighting the need for increased awareness, effective treatment, and preventative measures. In particular, smoking seems to be quite important for all” serious adverse outcomes, “so that’s a good place to start,” Dr. Ryom said at the Conference on Retroviruses & Opportunistic Infections.

Most of the 2,467 HIV patients with CKD were white men who have sex with men. At baseline, the median age was 60 years, and median CD4 cell count was above 500. One in three were smokers, 22.4% were HCV positive, and most had viral loads below 400 copies/mL. More than half of the patients were estimated to have died within 5 years of CKD diagnosis.

CKD was defined as two estimated glomerular filtration rates at or below 60 mL/min per 1.73 m² taken at least 3 months apart, or a 25% decrease in eGFR when patients entered the study at that level.

 

The subjects were all participants in the D:A:D project [Data Collection on Adverse Events of Anti-HIV Drugs], an ongoing international cohort study based at the University of Copenhagen, and funded by pharmaceutical companies, among others.

Dr. Ryom had no disclosures.

[email protected]

SOURCE: Ryom L et al. CROI, Abstract 75.

 

BOSTON – A lot of people do well with HIV thanks to potent antiretrovirals, but there’s still at least one group that needs extra attention: HIV patients with chronic kidney disease (CKD), according to Lene Ryom, MD, PhD, an HIV researcher at the University of Copenhagen.

She was the lead investigator on a review of 2,467 HIV patients with CKD – which is becoming more common in HIV as patients live longer – and 33,427 HIV patients without CKD.

decade3d/Thinkstock

At a median of 2.7 years after CKD diagnosis, 595 (24.1%) developed a serious clinical event, defined in the study as end-stage renal disease, end-stage liver disease, cardiovascular disease, malignancy, other AIDS events, or death. Almost 8% of patients developed a serious clinical event within a year of CKD diagnosis. Smoking, diabetes, dyslipidemia, body mass index below 18 kg/m², and poor HIV control were identified as modifiable risk factors.

The incidence of serious clinical events following CKD diagnosis was 68.9 events per 1,000 patient-years. Among the HIV patients without CKD, the incidence was 23 events per 1,000 patient-years.

“In an era when many HIV patients require much less management due to effective antiretroviral treatment, those living with CKD have a much higher burden of serious clinical events and require much closer monitoring. Modifiable risk factors ... play a central role in CKD morbidity and mortality, highlighting the need for increased awareness, effective treatment, and preventative measures. In particular, smoking seems to be quite important for all” serious adverse outcomes, “so that’s a good place to start,” Dr. Ryom said at the Conference on Retroviruses & Opportunistic Infections.

Most of the 2,467 HIV patients with CKD were white men who have sex with men. At baseline, the median age was 60 years, and median CD4 cell count was above 500. One in three were smokers, 22.4% were HCV positive, and most had viral loads below 400 copies/mL. More than half of the patients were estimated to have died within 5 years of CKD diagnosis.

CKD was defined as two estimated glomerular filtration rates at or below 60 mL/min per 1.73 m² taken at least 3 months apart, or a 25% decrease in eGFR when patients entered the study at that level.

 

The subjects were all participants in the D:A:D project [Data Collection on Adverse Events of Anti-HIV Drugs], an ongoing international cohort study based at the University of Copenhagen, and funded by pharmaceutical companies, among others.

Dr. Ryom had no disclosures.

[email protected]

SOURCE: Ryom L et al. CROI, Abstract 75.

 

BOSTON – A lot of people do well with HIV thanks to potent antiretrovirals, but there’s still at least one group that needs extra attention: HIV patients with chronic kidney disease (CKD), according to Lene Ryom, MD, PhD, an HIV researcher at the University of Copenhagen.

She was the lead investigator on a review of 2,467 HIV patients with CKD – which is becoming more common in HIV as patients live longer – and 33,427 HIV patients without CKD.

decade3d/Thinkstock

At a median of 2.7 years after CKD diagnosis, 595 (24.1%) developed a serious clinical event, defined in the study as end-stage renal disease, end-stage liver disease, cardiovascular disease, malignancy, other AIDS events, or death. Almost 8% of patients developed a serious clinical event within a year of CKD diagnosis. Smoking, diabetes, dyslipidemia, body mass index below 18 kg/m², and poor HIV control were identified as modifiable risk factors.

The incidence of serious clinical events following CKD diagnosis was 68.9 events per 1,000 patient-years. Among the HIV patients without CKD, the incidence was 23 events per 1,000 patient-years.

“In an era when many HIV patients require much less management due to effective antiretroviral treatment, those living with CKD have a much higher burden of serious clinical events and require much closer monitoring. Modifiable risk factors ... play a central role in CKD morbidity and mortality, highlighting the need for increased awareness, effective treatment, and preventative measures. In particular, smoking seems to be quite important for all” serious adverse outcomes, “so that’s a good place to start,” Dr. Ryom said at the Conference on Retroviruses & Opportunistic Infections.

Most of the 2,467 HIV patients with CKD were white men who have sex with men. At baseline, the median age was 60 years, and median CD4 cell count was above 500. One in three were smokers, 22.4% were HCV positive, and most had viral loads below 400 copies/mL. More than half of the patients were estimated to have died within 5 years of CKD diagnosis.

CKD was defined as two estimated glomerular filtration rates at or below 60 mL/min per 1.73 m² taken at least 3 months apart, or a 25% decrease in eGFR when patients entered the study at that level.

 

The subjects were all participants in the D:A:D project [Data Collection on Adverse Events of Anti-HIV Drugs], an ongoing international cohort study based at the University of Copenhagen, and funded by pharmaceutical companies, among others.

Dr. Ryom had no disclosures.

[email protected]

SOURCE: Ryom L et al. CROI, Abstract 75.

BOSTON – Fewer than 12% of HIV infected men will clear new hepatitis C infections on their own.

If they haven’t had a 2-log drop in their hepatitis C virus (HCV) RNA loads after a month, they aren’t going to clear the infection, and need direct-acting antiretrovirals (DAAs), according to an observational European study of 465 HIV patients with newly acquired HCV infections, almost all of them men who have sex with men (MSM).

The findings spoke to a hot topic at the Conference on Retroviruses & Opportunistic Infections (CROI): DAAs for acute HCV infection in patients with HIV. It’s a pressing problem; the incidence of sexually transmitted HCV among MSM with HIV is rising worldwide.

However, on both sides of the Atlantic, DAAs are indicated only for chronic HCV, which usually means infection for 6 months or more, because a third or so of patients will clear the infection on their own. The drugs are expensive, and reimbursements don’t generally kick in until after the waiting period.

That’s a problem with HIV coinfection, and not just because far fewer patients will rid themselves of the virus. HCV is most likely to be spread by sexual contact in the acute phase; allowing patients destined to become chronic carriers to linger without treatment means that the infection will probably spread to new partners, according to researchers at CROI,

Proactive measures could help. Swiss investigators reported a 50% drop in new HCV infections when HIV-positive MSM were screened for the infection then treated immediately with DAAs. Some at the meeting argued that HCV screening – and treatment – should be automatic for patients taking pre-exposure HIV prophylaxis, as well as for newly diagnosed HIV.

Several said that, on a population level, treatment in the acute phase would save money by preventing new infections. It’s also cheaper to treat in the acute phase because coinfected patients only need 8 weeks of DAA treatment rather than the usual 12-16 for chronic infection, according to another European study at the meeting.

“The idea of targeting acute HCV makes a lot of sense on all levels. If treatment” among patients with HIV “is two-thirds as long and more than two-thirds have persistent infection, there is no reason to hold” off just because of cost, said David Thomas, MD, director of the division of infectious diseases at Johns Hopkins University, Baltimore, who moderated the study presentations.

 

Eight weeks is enough

The efficacy of an 8-week treatment course was established in a study of 63 MSM in the Netherlands and Belgium. They were 47 years old, on average, and all but three were HIV positive; two-thirds had HCV genotype 1, and the rest had genotype 4, some with extremely high viral loads.

Subjects received grazoprevir/elbasvir (Zepatier) once daily for 8 weeks, beginning at a mean of 4.5 months after their estimated infection date, and all within 6 months. Twelve weeks after the end of therapy, 59 (94%) were negative for HCV RNA on blood tests. Three of the patients who were still positive for HCV had new infections; the remaining patient had relapsed, and was the only true treatment failure.

“We can say that 8 weeks of grazoprevir/elbasvir for acute HCV was safe, highly effective, and noninferior compared to studies with longer treatment. On an individual level, you can wait for spontaneous clearance, but on the population level, by treating all patients in the acute phase, you prevent spread of hepatitis C,” said lead investigator Anne Boerekamps, PhD, of Erasmus University Medical Center, Rotterdam, Netherlands.

 

The 2-log cutoff

“We are withholding effective treatment from people just because we’re concerned about the money,” said Christoph Boesecke, MD, of Bonn (Germany) University Hospital, who was the lead investigator in the study that found low spontaneous clearance rates with HIV coinfection.

Almost all the 465 subjects were on combination antiretroviral HIV therapy. Most had HCV genotype 1, but there were also type 3 and 4 cases. The investigators followed their subjects for at least a year after HCV infection. Just 55 (11.8%) cleared the infection on their own.

“Almost 90% of acutely infected patients face a chronic course. ... DAA drug labels, as well as clinical guidelines, need to be amended to allow usage of DAA during the acute phase of HCV infection in a high-risk population,” Dr. Boesecke and his team concluded.

Clearance was harbingered by a 2-log decline in HCV RNA by week 4. The 2-log drop cutoff is “the best predictor [we have] ... to identify patients” for early treatment. “There may be some patients you overtreat, but we have to keep in mind that we are not causing any harms with DAAs; maybe harms in terms of money, but not in terms of toxicity,” he said.

The message is beginning to get out. New European AIDS Clinical Society guidelines recommend DAA treatment for patients with HIV who don’t have a 2-log drop after a month.

 

‘Treatment as prevention’ works

The Swiss study added evidence to the frequent assertion at CROI that early treatment stops the spread of HCV.

The investigators screened 3,722 MSM from the Swiss HIV Cohort Study and found 178 (4.8%) men with replicating genotype 1 or 4 HCV infections. Of these cases, 31 were deemed incident and 147 chronic. Almost all the men agreed to treatment with standard-of-care DAAs, usually grazoprevir/elbasvir plus or minus ribavirin. Just about everyone had a sustained virologic response 12 weeks later.

The team rescreened the men after about a year, and found 28 infections; 16 were newly acquired, almost a 50% drop from baseline. The remaining 12 infections were chronic cases not treated earlier.

“Systemic screening followed by prompt DAA treatment can serve as a model to eliminate HCV in coinfected MSM,” said lead investigator Dominique Braun, MD, of the University of Zurich.

Dr. Boesecke is a consultant and/or speaker for AbbVie, Gilead Sciences, Janssen, Merck, and ViiV Healthcare. Dr. Thomas is a Merck consultant. Dr. Boerekamps and Dr. Braun’s studies were both funded by Merck, maker of elbasvir/grazoprevir.

[email protected]

SOURCE: Anne Boerekamps. 2018 CROI, Abstract 128. Christoph Boesecke. 2018 CROI, Abstract 129. Dominique Braun. 2018 CROI, Abstract 81LB.






 

BOSTON – Fewer than 12% of HIV infected men will clear new hepatitis C infections on their own.

If they haven’t had a 2-log drop in their hepatitis C virus (HCV) RNA loads after a month, they aren’t going to clear the infection, and need direct-acting antiretrovirals (DAAs), according to an observational European study of 465 HIV patients with newly acquired HCV infections, almost all of them men who have sex with men (MSM).

The findings spoke to a hot topic at the Conference on Retroviruses & Opportunistic Infections (CROI): DAAs for acute HCV infection in patients with HIV. It’s a pressing problem; the incidence of sexually transmitted HCV among MSM with HIV is rising worldwide.

However, on both sides of the Atlantic, DAAs are indicated only for chronic HCV, which usually means infection for 6 months or more, because a third or so of patients will clear the infection on their own. The drugs are expensive, and reimbursements don’t generally kick in until after the waiting period.

That’s a problem with HIV coinfection, and not just because far fewer patients will rid themselves of the virus. HCV is most likely to be spread by sexual contact in the acute phase; allowing patients destined to become chronic carriers to linger without treatment means that the infection will probably spread to new partners, according to researchers at CROI,

Proactive measures could help. Swiss investigators reported a 50% drop in new HCV infections when HIV-positive MSM were screened for the infection then treated immediately with DAAs. Some at the meeting argued that HCV screening – and treatment – should be automatic for patients taking pre-exposure HIV prophylaxis, as well as for newly diagnosed HIV.

Several said that, on a population level, treatment in the acute phase would save money by preventing new infections. It’s also cheaper to treat in the acute phase because coinfected patients only need 8 weeks of DAA treatment rather than the usual 12-16 for chronic infection, according to another European study at the meeting.

“The idea of targeting acute HCV makes a lot of sense on all levels. If treatment” among patients with HIV “is two-thirds as long and more than two-thirds have persistent infection, there is no reason to hold” off just because of cost, said David Thomas, MD, director of the division of infectious diseases at Johns Hopkins University, Baltimore, who moderated the study presentations.

 

Eight weeks is enough

The efficacy of an 8-week treatment course was established in a study of 63 MSM in the Netherlands and Belgium. They were 47 years old, on average, and all but three were HIV positive; two-thirds had HCV genotype 1, and the rest had genotype 4, some with extremely high viral loads.

Subjects received grazoprevir/elbasvir (Zepatier) once daily for 8 weeks, beginning at a mean of 4.5 months after their estimated infection date, and all within 6 months. Twelve weeks after the end of therapy, 59 (94%) were negative for HCV RNA on blood tests. Three of the patients who were still positive for HCV had new infections; the remaining patient had relapsed, and was the only true treatment failure.

“We can say that 8 weeks of grazoprevir/elbasvir for acute HCV was safe, highly effective, and noninferior compared to studies with longer treatment. On an individual level, you can wait for spontaneous clearance, but on the population level, by treating all patients in the acute phase, you prevent spread of hepatitis C,” said lead investigator Anne Boerekamps, PhD, of Erasmus University Medical Center, Rotterdam, Netherlands.

 

The 2-log cutoff

“We are withholding effective treatment from people just because we’re concerned about the money,” said Christoph Boesecke, MD, of Bonn (Germany) University Hospital, who was the lead investigator in the study that found low spontaneous clearance rates with HIV coinfection.

Almost all the 465 subjects were on combination antiretroviral HIV therapy. Most had HCV genotype 1, but there were also type 3 and 4 cases. The investigators followed their subjects for at least a year after HCV infection. Just 55 (11.8%) cleared the infection on their own.

“Almost 90% of acutely infected patients face a chronic course. ... DAA drug labels, as well as clinical guidelines, need to be amended to allow usage of DAA during the acute phase of HCV infection in a high-risk population,” Dr. Boesecke and his team concluded.

Clearance was harbingered by a 2-log decline in HCV RNA by week 4. The 2-log drop cutoff is “the best predictor [we have] ... to identify patients” for early treatment. “There may be some patients you overtreat, but we have to keep in mind that we are not causing any harms with DAAs; maybe harms in terms of money, but not in terms of toxicity,” he said.

The message is beginning to get out. New European AIDS Clinical Society guidelines recommend DAA treatment for patients with HIV who don’t have a 2-log drop after a month.

 

‘Treatment as prevention’ works

The Swiss study added evidence to the frequent assertion at CROI that early treatment stops the spread of HCV.

The investigators screened 3,722 MSM from the Swiss HIV Cohort Study and found 178 (4.8%) men with replicating genotype 1 or 4 HCV infections. Of these cases, 31 were deemed incident and 147 chronic. Almost all the men agreed to treatment with standard-of-care DAAs, usually grazoprevir/elbasvir plus or minus ribavirin. Just about everyone had a sustained virologic response 12 weeks later.

The team rescreened the men after about a year, and found 28 infections; 16 were newly acquired, almost a 50% drop from baseline. The remaining 12 infections were chronic cases not treated earlier.

“Systemic screening followed by prompt DAA treatment can serve as a model to eliminate HCV in coinfected MSM,” said lead investigator Dominique Braun, MD, of the University of Zurich.

Dr. Boesecke is a consultant and/or speaker for AbbVie, Gilead Sciences, Janssen, Merck, and ViiV Healthcare. Dr. Thomas is a Merck consultant. Dr. Boerekamps and Dr. Braun’s studies were both funded by Merck, maker of elbasvir/grazoprevir.

[email protected]

SOURCE: Anne Boerekamps. 2018 CROI, Abstract 128. Christoph Boesecke. 2018 CROI, Abstract 129. Dominique Braun. 2018 CROI, Abstract 81LB.






 

BOSTON – Fewer than 12% of HIV infected men will clear new hepatitis C infections on their own.

If they haven’t had a 2-log drop in their hepatitis C virus (HCV) RNA loads after a month, they aren’t going to clear the infection, and need direct-acting antiretrovirals (DAAs), according to an observational European study of 465 HIV patients with newly acquired HCV infections, almost all of them men who have sex with men (MSM).

The findings spoke to a hot topic at the Conference on Retroviruses & Opportunistic Infections (CROI): DAAs for acute HCV infection in patients with HIV. It’s a pressing problem; the incidence of sexually transmitted HCV among MSM with HIV is rising worldwide.

However, on both sides of the Atlantic, DAAs are indicated only for chronic HCV, which usually means infection for 6 months or more, because a third or so of patients will clear the infection on their own. The drugs are expensive, and reimbursements don’t generally kick in until after the waiting period.

That’s a problem with HIV coinfection, and not just because far fewer patients will rid themselves of the virus. HCV is most likely to be spread by sexual contact in the acute phase; allowing patients destined to become chronic carriers to linger without treatment means that the infection will probably spread to new partners, according to researchers at CROI,

Proactive measures could help. Swiss investigators reported a 50% drop in new HCV infections when HIV-positive MSM were screened for the infection then treated immediately with DAAs. Some at the meeting argued that HCV screening – and treatment – should be automatic for patients taking pre-exposure HIV prophylaxis, as well as for newly diagnosed HIV.

Several said that, on a population level, treatment in the acute phase would save money by preventing new infections. It’s also cheaper to treat in the acute phase because coinfected patients only need 8 weeks of DAA treatment rather than the usual 12-16 for chronic infection, according to another European study at the meeting.

“The idea of targeting acute HCV makes a lot of sense on all levels. If treatment” among patients with HIV “is two-thirds as long and more than two-thirds have persistent infection, there is no reason to hold” off just because of cost, said David Thomas, MD, director of the division of infectious diseases at Johns Hopkins University, Baltimore, who moderated the study presentations.

 

Eight weeks is enough

The efficacy of an 8-week treatment course was established in a study of 63 MSM in the Netherlands and Belgium. They were 47 years old, on average, and all but three were HIV positive; two-thirds had HCV genotype 1, and the rest had genotype 4, some with extremely high viral loads.

Subjects received grazoprevir/elbasvir (Zepatier) once daily for 8 weeks, beginning at a mean of 4.5 months after their estimated infection date, and all within 6 months. Twelve weeks after the end of therapy, 59 (94%) were negative for HCV RNA on blood tests. Three of the patients who were still positive for HCV had new infections; the remaining patient had relapsed, and was the only true treatment failure.

“We can say that 8 weeks of grazoprevir/elbasvir for acute HCV was safe, highly effective, and noninferior compared to studies with longer treatment. On an individual level, you can wait for spontaneous clearance, but on the population level, by treating all patients in the acute phase, you prevent spread of hepatitis C,” said lead investigator Anne Boerekamps, PhD, of Erasmus University Medical Center, Rotterdam, Netherlands.

 

The 2-log cutoff

“We are withholding effective treatment from people just because we’re concerned about the money,” said Christoph Boesecke, MD, of Bonn (Germany) University Hospital, who was the lead investigator in the study that found low spontaneous clearance rates with HIV coinfection.

Almost all the 465 subjects were on combination antiretroviral HIV therapy. Most had HCV genotype 1, but there were also type 3 and 4 cases. The investigators followed their subjects for at least a year after HCV infection. Just 55 (11.8%) cleared the infection on their own.

“Almost 90% of acutely infected patients face a chronic course. ... DAA drug labels, as well as clinical guidelines, need to be amended to allow usage of DAA during the acute phase of HCV infection in a high-risk population,” Dr. Boesecke and his team concluded.

Clearance was harbingered by a 2-log decline in HCV RNA by week 4. The 2-log drop cutoff is “the best predictor [we have] ... to identify patients” for early treatment. “There may be some patients you overtreat, but we have to keep in mind that we are not causing any harms with DAAs; maybe harms in terms of money, but not in terms of toxicity,” he said.

The message is beginning to get out. New European AIDS Clinical Society guidelines recommend DAA treatment for patients with HIV who don’t have a 2-log drop after a month.

 

‘Treatment as prevention’ works

The Swiss study added evidence to the frequent assertion at CROI that early treatment stops the spread of HCV.

The investigators screened 3,722 MSM from the Swiss HIV Cohort Study and found 178 (4.8%) men with replicating genotype 1 or 4 HCV infections. Of these cases, 31 were deemed incident and 147 chronic. Almost all the men agreed to treatment with standard-of-care DAAs, usually grazoprevir/elbasvir plus or minus ribavirin. Just about everyone had a sustained virologic response 12 weeks later.

The team rescreened the men after about a year, and found 28 infections; 16 were newly acquired, almost a 50% drop from baseline. The remaining 12 infections were chronic cases not treated earlier.

“Systemic screening followed by prompt DAA treatment can serve as a model to eliminate HCV in coinfected MSM,” said lead investigator Dominique Braun, MD, of the University of Zurich.

Dr. Boesecke is a consultant and/or speaker for AbbVie, Gilead Sciences, Janssen, Merck, and ViiV Healthcare. Dr. Thomas is a Merck consultant. Dr. Boerekamps and Dr. Braun’s studies were both funded by Merck, maker of elbasvir/grazoprevir.

[email protected]

SOURCE: Anne Boerekamps. 2018 CROI, Abstract 128. Christoph Boesecke. 2018 CROI, Abstract 129. Dominique Braun. 2018 CROI, Abstract 81LB.






 

 

BOSTON – There was no sign of HCV infection more than a year after 10 patients at Johns Hopkins University, Baltimore, received kidneys from HCV-infected donors.

The patients were treated with prophylactic direct-acting antivirals (DAAs) before and after the procedure. Low levels of hepatitis C RNA were detected shortly after transplant in five patients, but it became undetectable within a week. None of the patients developed any clinical signs of chronic hepatitis C infection, and the transplanted kidneys functioned well.

Alex Otto/MDedge News

Until now, organs from HCV-infected donors were usually discarded if they were retrieved at all. Around 500 hepatitis C–positive kidneys are thrown out in the United States every year.

The number of organs from HCV–infected people is on the rise because of the opioid epidemic. Organ donations from drug overdoses used to be rare, but about 10% of transplanted organs are now from an overdose death, and about 30% of people who overdose have HCV. “These are young people who could donate hearts, lungs, and kidneys, and their parents and families want them to be able to make that gift of life,” said lead investigator Christine Durand, MD, of Johns Hopkins University, Baltimore.

DAAs make that possible because they cure HCV. “If the success of these transplants continues, it could pave the way for other hepatitis C–positive organs, including hearts and livers, to be transplanted as well,” Dr. Durand and her colleagues said in a press release from Johns Hopkins.

The 10 patients were over age 50 years, with a mean age of 71 years, and had been on the kidney transplant list for an average of 4 months. The HCV-positive donors were 13-50 years old with no evidence of kidney disease (Ann Intern Med. 2018 Mar 6. doi: 10.7326/M17-2871)..

Each recipient received a dose of grazoprevir/elbasvir (Zepatier) before transplant and stayed on the medication daily for 12 weeks postop. Three patients also took a daily dose of sofosbuvir (Sovaldi) because of the strain of HCV in the donor kidney. Maybe 8 weeks of treatment, or even 4, is enough, Dr. Durand said at the Conference on Retroviruses and Opportunistic Infections.

 

“I am thrilled to report that at 1 year post transplant 10 out of 10 of these recipients are HCV free, and they are doing very well. Prophylactic treatment may mean that more individuals can receive transplants from hepatitis C–infected donors without transmission of infection. The use of organs from infected donors can help everyone on the transplant list by shortening wait times and shortening the wait list,” she said.

“I’m not surprised by the results of the study because these DAAs are highly effective, but I was surprised by how willing patients were to sign up for the study. They said it was a no-brainer. In our region, if you need a kidney, you are going to wait for up to 5 years, and you may die while you are waiting. If you can accept a hepatitis C–positive donor organ, you will get transplanted in a matter of weeks,” she said.

“I hope providers tell their patients with HCV that they can register as organ donors,” she said.

The work is being supported primarily by Merck Sharp & Dohme. Dr. Durand is an advisor to Bristol-Meyers Squibb, Gilead Sciences, and Merck Pharmaceuticals and has research funding from the companies.

[email protected]

SOURCE: Durand CM et al. Ann Intern Med. 2018 Mar 6. doi: 10.7326/M17-2871.

 

BOSTON – There was no sign of HCV infection more than a year after 10 patients at Johns Hopkins University, Baltimore, received kidneys from HCV-infected donors.

The patients were treated with prophylactic direct-acting antivirals (DAAs) before and after the procedure. Low levels of hepatitis C RNA were detected shortly after transplant in five patients, but it became undetectable within a week. None of the patients developed any clinical signs of chronic hepatitis C infection, and the transplanted kidneys functioned well.

Alex Otto/MDedge News

Until now, organs from HCV-infected donors were usually discarded if they were retrieved at all. Around 500 hepatitis C–positive kidneys are thrown out in the United States every year.

The number of organs from HCV–infected people is on the rise because of the opioid epidemic. Organ donations from drug overdoses used to be rare, but about 10% of transplanted organs are now from an overdose death, and about 30% of people who overdose have HCV. “These are young people who could donate hearts, lungs, and kidneys, and their parents and families want them to be able to make that gift of life,” said lead investigator Christine Durand, MD, of Johns Hopkins University, Baltimore.

DAAs make that possible because they cure HCV. “If the success of these transplants continues, it could pave the way for other hepatitis C–positive organs, including hearts and livers, to be transplanted as well,” Dr. Durand and her colleagues said in a press release from Johns Hopkins.

The 10 patients were over age 50 years, with a mean age of 71 years, and had been on the kidney transplant list for an average of 4 months. The HCV-positive donors were 13-50 years old with no evidence of kidney disease (Ann Intern Med. 2018 Mar 6. doi: 10.7326/M17-2871)..

Each recipient received a dose of grazoprevir/elbasvir (Zepatier) before transplant and stayed on the medication daily for 12 weeks postop. Three patients also took a daily dose of sofosbuvir (Sovaldi) because of the strain of HCV in the donor kidney. Maybe 8 weeks of treatment, or even 4, is enough, Dr. Durand said at the Conference on Retroviruses and Opportunistic Infections.

 

“I am thrilled to report that at 1 year post transplant 10 out of 10 of these recipients are HCV free, and they are doing very well. Prophylactic treatment may mean that more individuals can receive transplants from hepatitis C–infected donors without transmission of infection. The use of organs from infected donors can help everyone on the transplant list by shortening wait times and shortening the wait list,” she said.

“I’m not surprised by the results of the study because these DAAs are highly effective, but I was surprised by how willing patients were to sign up for the study. They said it was a no-brainer. In our region, if you need a kidney, you are going to wait for up to 5 years, and you may die while you are waiting. If you can accept a hepatitis C–positive donor organ, you will get transplanted in a matter of weeks,” she said.

“I hope providers tell their patients with HCV that they can register as organ donors,” she said.

The work is being supported primarily by Merck Sharp & Dohme. Dr. Durand is an advisor to Bristol-Meyers Squibb, Gilead Sciences, and Merck Pharmaceuticals and has research funding from the companies.

[email protected]

SOURCE: Durand CM et al. Ann Intern Med. 2018 Mar 6. doi: 10.7326/M17-2871.

 

BOSTON – There was no sign of HCV infection more than a year after 10 patients at Johns Hopkins University, Baltimore, received kidneys from HCV-infected donors.

The patients were treated with prophylactic direct-acting antivirals (DAAs) before and after the procedure. Low levels of hepatitis C RNA were detected shortly after transplant in five patients, but it became undetectable within a week. None of the patients developed any clinical signs of chronic hepatitis C infection, and the transplanted kidneys functioned well.

Alex Otto/MDedge News

Until now, organs from HCV-infected donors were usually discarded if they were retrieved at all. Around 500 hepatitis C–positive kidneys are thrown out in the United States every year.

The number of organs from HCV–infected people is on the rise because of the opioid epidemic. Organ donations from drug overdoses used to be rare, but about 10% of transplanted organs are now from an overdose death, and about 30% of people who overdose have HCV. “These are young people who could donate hearts, lungs, and kidneys, and their parents and families want them to be able to make that gift of life,” said lead investigator Christine Durand, MD, of Johns Hopkins University, Baltimore.

DAAs make that possible because they cure HCV. “If the success of these transplants continues, it could pave the way for other hepatitis C–positive organs, including hearts and livers, to be transplanted as well,” Dr. Durand and her colleagues said in a press release from Johns Hopkins.

The 10 patients were over age 50 years, with a mean age of 71 years, and had been on the kidney transplant list for an average of 4 months. The HCV-positive donors were 13-50 years old with no evidence of kidney disease (Ann Intern Med. 2018 Mar 6. doi: 10.7326/M17-2871)..

Each recipient received a dose of grazoprevir/elbasvir (Zepatier) before transplant and stayed on the medication daily for 12 weeks postop. Three patients also took a daily dose of sofosbuvir (Sovaldi) because of the strain of HCV in the donor kidney. Maybe 8 weeks of treatment, or even 4, is enough, Dr. Durand said at the Conference on Retroviruses and Opportunistic Infections.

 

“I am thrilled to report that at 1 year post transplant 10 out of 10 of these recipients are HCV free, and they are doing very well. Prophylactic treatment may mean that more individuals can receive transplants from hepatitis C–infected donors without transmission of infection. The use of organs from infected donors can help everyone on the transplant list by shortening wait times and shortening the wait list,” she said.

“I’m not surprised by the results of the study because these DAAs are highly effective, but I was surprised by how willing patients were to sign up for the study. They said it was a no-brainer. In our region, if you need a kidney, you are going to wait for up to 5 years, and you may die while you are waiting. If you can accept a hepatitis C–positive donor organ, you will get transplanted in a matter of weeks,” she said.

“I hope providers tell their patients with HCV that they can register as organ donors,” she said.

The work is being supported primarily by Merck Sharp & Dohme. Dr. Durand is an advisor to Bristol-Meyers Squibb, Gilead Sciences, and Merck Pharmaceuticals and has research funding from the companies.

[email protected]

SOURCE: Durand CM et al. Ann Intern Med. 2018 Mar 6. doi: 10.7326/M17-2871.

 

BOSTON – Current daily doses of rifampin for treating pulmonary tuberculosis may be too low and could be safely increased, results of a randomized phase 2 study suggest.

“Back in the 1970s, rifampin was an expensive drug, and attempts to shorten TB therapy using higher but intermittent doses of rifampin were unsuccessful at that time because of increased toxicity. That line of inquiry was essentially dormant for 40 years,” said Gustavo Velásquez, MD, from Brigham & Women’s Hospital in Boston.

Neil Osterweil/MDedge News

More recent controlled trials have evaluated higher daily doses of rifampin, but none thus far have looked at concentration-dependent drug activity in Latin American patients or at efficacy as a function of the parameter that is thought to best predict rifampin activity, which is the ratio of the area under the curve to the maximum inhibitory concentration (AUC/MIC) of rifampin, he said at the Conference on Retroviruses and Opportunistic Infections.

To get a better idea of optimal rifampin dosing for the treatment of pulmonary TB, Dr. Velásquez and his colleagues conducted the HIRIF (High-Dose Rifampin in Patients With TB) trial. The phase 2 study was designed to evaluate the pharmacokinetics, efficacy, and safety of higher daily rifampin doses for pulmonary TB.

They looked at the three parameters across three treatments arms: 10 mg/kg rifampin (the current standard of care), 15 mg/kg, or 20 mg/kg.

Patients in Peru were screened, enrolled, and randomized in cohorts of 60 patients each to one of the three specified dose levels, which they received either as additional rifampin tablets or placebo for the first 8 weeks of treatment, after which all patients were continued on rifampin 10 mg/kg to complete a 6-month regimen. All patients were followed for an additional 6 months to for assessment of TB recurrence.

Rifampin total doses ranged from as low as 300 mg for patients in the 30 kg-37 kg weight range, to as high as 1,500 mg for those weighing more than 70 kg.

 

The efficacy analysis was by modified intention to treat, excluding 6 patients who had insufficient log­₁₀ colony-forming units (CFUs) of TB, and a per-protocol analysis excluding an additional 42 patients whose doses of rifampin were affected by three study halts for adverse events. After each halt and review by the data-safety monitoring board, the trial was allowed to resume, but because enrollment and experimental dosing also were suspended, patients in the 15- and 20-mg/kg arms received 10 mg/kg during the 2-5 week halts. The number of patients in the 10-, 15-, and 20-mg/kg doses included in the per-protocol analysis were 56, 38, and 38, respectively,

Pharmacokinetic evidence from this study, previously published, showed that the median maximum drug concentration (C_max) in serum in the experimental arms reached the lower end of the targeted range of 8 mcg/mL or greater, whereas the median in the standard-of-care arm was 6.2 mcg/mL. Only 33% of patients in the 10-mg/kg arm reached the minimum 8-mcg/mL level, Dr. Velásquez noted, vs. 72% and 81% of patients in the 15- and 20-mg/kg doses, respectively.

In the modified intention-to-treat population, for every 5-mg/kg increase in rifampin dose, there was a nonsignificant trend toward faster decline in TB CFUs in sputum. Similarly, for every 1-log increase in rifampin AUC/MIC, there was a trend, albeit nonsignificant, toward faster decline.

However, in patients in the per-protocol analysis, every 5-mg/kg dose increase and 1-log increase in rifampin AUC was associated with significantly faster declines in CFUs (P = .022 and .011, respectively).

 

An analysis of treatment outcomes at 12 months, a secondary endpoint, showed that there were five cases of treatment failure, including three in the control arm and one each in 15- and 20-mg/kg arms, and six cases of recurrence after cure, which occurred in three, one, and two patients, respectively,

The safety analysis by intention-to-treat showed that the incidence of grade 2 or greater rifampin-related adverse events (AEs) were 43.3%, 51.7%, and 38.3% in the 10-, 15-, and 20-mg/kg doses, differences that were not statistically significant.

In addition, there were no significant differences among the treatment arms in either time to first grade 2 or greater rifampin-related AEs, the occurrence of one or more grade 2 or greater hepatic rifampin-AEs, or time to first hepatic rifampin-related AEs of grade 2 or above.

Dr. Velásquez noted that the study was limited by the possibility that the study halts could have biased efficacy effect estimates toward null and by differences in weight distribution among the three treatment arms.

 

“This actually is the first trial that shows not only a dose response of rifampin but also an exposure response of rifampin in combination therapy,” he said. “Our study supports that even higher doses of rifampin beyond what we studied of 20 mg/kg should be studied for potential treatment shortening.” The evidence also suggests that the current 10-mg/kg dose is low and could be safely increased to a 15- or 20-mg/kg dose, he concluded.

In a media briefing following the presentation, moderator Constance Benson, MD, from the University of California San Diego, who was not involved in the study, commented that with “high-dose rifampin, I think we have a really very robust body of literature to which this study can be added, demonstrating the safety of high-dose rifampin in the context of TB treatment.”

“There are some circumstances where I think using a much higher dose than we’ve been using would be an appropriate thing to do,” she added.

Examples of patients who might benefit include patients with disseminated TB or people with more serious TB than the average case, she said.

 

The study was supported by the National Institute of Allergy and Infectious Diseases. Dr. Velásquez and Dr. Benson reported no relevant conflicts of interest.

SOURCE: Velásquez GE et al. CROI 2018, Abstract 39LB.

 

BOSTON – Current daily doses of rifampin for treating pulmonary tuberculosis may be too low and could be safely increased, results of a randomized phase 2 study suggest.

“Back in the 1970s, rifampin was an expensive drug, and attempts to shorten TB therapy using higher but intermittent doses of rifampin were unsuccessful at that time because of increased toxicity. That line of inquiry was essentially dormant for 40 years,” said Gustavo Velásquez, MD, from Brigham & Women’s Hospital in Boston.

Neil Osterweil/MDedge News

More recent controlled trials have evaluated higher daily doses of rifampin, but none thus far have looked at concentration-dependent drug activity in Latin American patients or at efficacy as a function of the parameter that is thought to best predict rifampin activity, which is the ratio of the area under the curve to the maximum inhibitory concentration (AUC/MIC) of rifampin, he said at the Conference on Retroviruses and Opportunistic Infections.

To get a better idea of optimal rifampin dosing for the treatment of pulmonary TB, Dr. Velásquez and his colleagues conducted the HIRIF (High-Dose Rifampin in Patients With TB) trial. The phase 2 study was designed to evaluate the pharmacokinetics, efficacy, and safety of higher daily rifampin doses for pulmonary TB.

They looked at the three parameters across three treatments arms: 10 mg/kg rifampin (the current standard of care), 15 mg/kg, or 20 mg/kg.

Patients in Peru were screened, enrolled, and randomized in cohorts of 60 patients each to one of the three specified dose levels, which they received either as additional rifampin tablets or placebo for the first 8 weeks of treatment, after which all patients were continued on rifampin 10 mg/kg to complete a 6-month regimen. All patients were followed for an additional 6 months to for assessment of TB recurrence.

Rifampin total doses ranged from as low as 300 mg for patients in the 30 kg-37 kg weight range, to as high as 1,500 mg for those weighing more than 70 kg.

 

The efficacy analysis was by modified intention to treat, excluding 6 patients who had insufficient log­₁₀ colony-forming units (CFUs) of TB, and a per-protocol analysis excluding an additional 42 patients whose doses of rifampin were affected by three study halts for adverse events. After each halt and review by the data-safety monitoring board, the trial was allowed to resume, but because enrollment and experimental dosing also were suspended, patients in the 15- and 20-mg/kg arms received 10 mg/kg during the 2-5 week halts. The number of patients in the 10-, 15-, and 20-mg/kg doses included in the per-protocol analysis were 56, 38, and 38, respectively,

Pharmacokinetic evidence from this study, previously published, showed that the median maximum drug concentration (C_max) in serum in the experimental arms reached the lower end of the targeted range of 8 mcg/mL or greater, whereas the median in the standard-of-care arm was 6.2 mcg/mL. Only 33% of patients in the 10-mg/kg arm reached the minimum 8-mcg/mL level, Dr. Velásquez noted, vs. 72% and 81% of patients in the 15- and 20-mg/kg doses, respectively.

In the modified intention-to-treat population, for every 5-mg/kg increase in rifampin dose, there was a nonsignificant trend toward faster decline in TB CFUs in sputum. Similarly, for every 1-log increase in rifampin AUC/MIC, there was a trend, albeit nonsignificant, toward faster decline.

However, in patients in the per-protocol analysis, every 5-mg/kg dose increase and 1-log increase in rifampin AUC was associated with significantly faster declines in CFUs (P = .022 and .011, respectively).

 

An analysis of treatment outcomes at 12 months, a secondary endpoint, showed that there were five cases of treatment failure, including three in the control arm and one each in 15- and 20-mg/kg arms, and six cases of recurrence after cure, which occurred in three, one, and two patients, respectively,

The safety analysis by intention-to-treat showed that the incidence of grade 2 or greater rifampin-related adverse events (AEs) were 43.3%, 51.7%, and 38.3% in the 10-, 15-, and 20-mg/kg doses, differences that were not statistically significant.

In addition, there were no significant differences among the treatment arms in either time to first grade 2 or greater rifampin-related AEs, the occurrence of one or more grade 2 or greater hepatic rifampin-AEs, or time to first hepatic rifampin-related AEs of grade 2 or above.

Dr. Velásquez noted that the study was limited by the possibility that the study halts could have biased efficacy effect estimates toward null and by differences in weight distribution among the three treatment arms.

 

“This actually is the first trial that shows not only a dose response of rifampin but also an exposure response of rifampin in combination therapy,” he said. “Our study supports that even higher doses of rifampin beyond what we studied of 20 mg/kg should be studied for potential treatment shortening.” The evidence also suggests that the current 10-mg/kg dose is low and could be safely increased to a 15- or 20-mg/kg dose, he concluded.

In a media briefing following the presentation, moderator Constance Benson, MD, from the University of California San Diego, who was not involved in the study, commented that with “high-dose rifampin, I think we have a really very robust body of literature to which this study can be added, demonstrating the safety of high-dose rifampin in the context of TB treatment.”

“There are some circumstances where I think using a much higher dose than we’ve been using would be an appropriate thing to do,” she added.

Examples of patients who might benefit include patients with disseminated TB or people with more serious TB than the average case, she said.

 

The study was supported by the National Institute of Allergy and Infectious Diseases. Dr. Velásquez and Dr. Benson reported no relevant conflicts of interest.

SOURCE: Velásquez GE et al. CROI 2018, Abstract 39LB.

 

BOSTON – Current daily doses of rifampin for treating pulmonary tuberculosis may be too low and could be safely increased, results of a randomized phase 2 study suggest.

“Back in the 1970s, rifampin was an expensive drug, and attempts to shorten TB therapy using higher but intermittent doses of rifampin were unsuccessful at that time because of increased toxicity. That line of inquiry was essentially dormant for 40 years,” said Gustavo Velásquez, MD, from Brigham & Women’s Hospital in Boston.

Neil Osterweil/MDedge News

More recent controlled trials have evaluated higher daily doses of rifampin, but none thus far have looked at concentration-dependent drug activity in Latin American patients or at efficacy as a function of the parameter that is thought to best predict rifampin activity, which is the ratio of the area under the curve to the maximum inhibitory concentration (AUC/MIC) of rifampin, he said at the Conference on Retroviruses and Opportunistic Infections.

To get a better idea of optimal rifampin dosing for the treatment of pulmonary TB, Dr. Velásquez and his colleagues conducted the HIRIF (High-Dose Rifampin in Patients With TB) trial. The phase 2 study was designed to evaluate the pharmacokinetics, efficacy, and safety of higher daily rifampin doses for pulmonary TB.

They looked at the three parameters across three treatments arms: 10 mg/kg rifampin (the current standard of care), 15 mg/kg, or 20 mg/kg.

Patients in Peru were screened, enrolled, and randomized in cohorts of 60 patients each to one of the three specified dose levels, which they received either as additional rifampin tablets or placebo for the first 8 weeks of treatment, after which all patients were continued on rifampin 10 mg/kg to complete a 6-month regimen. All patients were followed for an additional 6 months to for assessment of TB recurrence.

Rifampin total doses ranged from as low as 300 mg for patients in the 30 kg-37 kg weight range, to as high as 1,500 mg for those weighing more than 70 kg.

 

The efficacy analysis was by modified intention to treat, excluding 6 patients who had insufficient log­₁₀ colony-forming units (CFUs) of TB, and a per-protocol analysis excluding an additional 42 patients whose doses of rifampin were affected by three study halts for adverse events. After each halt and review by the data-safety monitoring board, the trial was allowed to resume, but because enrollment and experimental dosing also were suspended, patients in the 15- and 20-mg/kg arms received 10 mg/kg during the 2-5 week halts. The number of patients in the 10-, 15-, and 20-mg/kg doses included in the per-protocol analysis were 56, 38, and 38, respectively,

Pharmacokinetic evidence from this study, previously published, showed that the median maximum drug concentration (C_max) in serum in the experimental arms reached the lower end of the targeted range of 8 mcg/mL or greater, whereas the median in the standard-of-care arm was 6.2 mcg/mL. Only 33% of patients in the 10-mg/kg arm reached the minimum 8-mcg/mL level, Dr. Velásquez noted, vs. 72% and 81% of patients in the 15- and 20-mg/kg doses, respectively.

In the modified intention-to-treat population, for every 5-mg/kg increase in rifampin dose, there was a nonsignificant trend toward faster decline in TB CFUs in sputum. Similarly, for every 1-log increase in rifampin AUC/MIC, there was a trend, albeit nonsignificant, toward faster decline.

However, in patients in the per-protocol analysis, every 5-mg/kg dose increase and 1-log increase in rifampin AUC was associated with significantly faster declines in CFUs (P = .022 and .011, respectively).

 

An analysis of treatment outcomes at 12 months, a secondary endpoint, showed that there were five cases of treatment failure, including three in the control arm and one each in 15- and 20-mg/kg arms, and six cases of recurrence after cure, which occurred in three, one, and two patients, respectively,

The safety analysis by intention-to-treat showed that the incidence of grade 2 or greater rifampin-related adverse events (AEs) were 43.3%, 51.7%, and 38.3% in the 10-, 15-, and 20-mg/kg doses, differences that were not statistically significant.

In addition, there were no significant differences among the treatment arms in either time to first grade 2 or greater rifampin-related AEs, the occurrence of one or more grade 2 or greater hepatic rifampin-AEs, or time to first hepatic rifampin-related AEs of grade 2 or above.

Dr. Velásquez noted that the study was limited by the possibility that the study halts could have biased efficacy effect estimates toward null and by differences in weight distribution among the three treatment arms.

 

“This actually is the first trial that shows not only a dose response of rifampin but also an exposure response of rifampin in combination therapy,” he said. “Our study supports that even higher doses of rifampin beyond what we studied of 20 mg/kg should be studied for potential treatment shortening.” The evidence also suggests that the current 10-mg/kg dose is low and could be safely increased to a 15- or 20-mg/kg dose, he concluded.

In a media briefing following the presentation, moderator Constance Benson, MD, from the University of California San Diego, who was not involved in the study, commented that with “high-dose rifampin, I think we have a really very robust body of literature to which this study can be added, demonstrating the safety of high-dose rifampin in the context of TB treatment.”

“There are some circumstances where I think using a much higher dose than we’ve been using would be an appropriate thing to do,” she added.

Examples of patients who might benefit include patients with disseminated TB or people with more serious TB than the average case, she said.

 

The study was supported by the National Institute of Allergy and Infectious Diseases. Dr. Velásquez and Dr. Benson reported no relevant conflicts of interest.

SOURCE: Velásquez GE et al. CROI 2018, Abstract 39LB.

 

BOSTON – For infants with HIV infection, baseline immune function and birth health appear to influence viral control after the discontinuation of antiretroviral therapy (ART), an analysis of data from the landmark CHER trial shows.

Among 183 children diagnosed with HIV between 6 and 12 weeks of age who were started on early, time-limited ART, longer time to viral rebound after treatment discontinuation was associated with higher baseline CD4 percentages, higher birth weight, and with achievement of viral suppression within 40 weeks of starting on ART, reported Man Chan, PhD, of the Medical Research Council clinical trials unit at University College London.

patrisyu/Thinkstock

“On the other hand, we did not find an association between age at ART start and length of therapy with a longer time to rebound. However, we should interpret these results with some caution, obviously because the range of ages at ART start was quite small, from 6-12 weeks, so we didn’t really have enough spread in the data to enable us to draw solid conclusions,” she said at the annual Conference on Retroviruses & Opportunistic Infections.

The CHER trial compared South African infants with HIV on either 40 or 96 weeks of immediate ART with those on deferred ART. The results showed that early time-limited ART was associated with better clinical and immunologic outcomes than was deferred ART and influenced a change in treatment guidelines (Lancet 2013 Nov 9;382[9904]:1555-63).

In the current analysis, investigators examined viral control after treatment interruption in early-treated children and looked for factors that could influence time to viral rebound after ART cessation.

They measured viral load from stored samples at 1.8 weeks after ART interruption and then every 12 weeks thereafter. They defined viral rebound as two consecutive samples with 400 or more copies/mL.

Of the 183 children in the sample, 177 had a rebound; the remaining six children were censored from the analysis, five because they had restarted ART, and one child who remained in viral suppression with an undetectable viral load and was asymptomatic for 8.5 years off ART.

 

The estimated cumulative probability of rebound was 70% at 2 months following ART interruption, 80% at 4 months, 94% at 6 months, and 99% at 8 months.

In multivariable analysis, factors significantly associated with longer time to viral rebound included higher baseline CD4 counts (P = .03), higher birth weight (P = .032), and viral suppression within 40 weeks of starting on ART (P = .028)

In contrast, there were no significant associations with other factors in the multivariate model, including sex, baseline viral load, baseline CD8 percentage, HIV stage, status of therapy to prevent mother-to-child transmission, age at ART initiation, length of therapy, or treatment center.

Sensitivity analyses of a few cases in which there was a 4-7 month gap between rebound and the last viral load below 400 copies/mL before rebound showed similar results, Dr. Chan noted.

 

The study was the U.S. National Institutes of Health. Dr. Chan reported having nothing to disclose.

SOURCE: Violari A et al. CROI 2018, Abstract 137

 

BOSTON – For infants with HIV infection, baseline immune function and birth health appear to influence viral control after the discontinuation of antiretroviral therapy (ART), an analysis of data from the landmark CHER trial shows.

Among 183 children diagnosed with HIV between 6 and 12 weeks of age who were started on early, time-limited ART, longer time to viral rebound after treatment discontinuation was associated with higher baseline CD4 percentages, higher birth weight, and with achievement of viral suppression within 40 weeks of starting on ART, reported Man Chan, PhD, of the Medical Research Council clinical trials unit at University College London.

patrisyu/Thinkstock

“On the other hand, we did not find an association between age at ART start and length of therapy with a longer time to rebound. However, we should interpret these results with some caution, obviously because the range of ages at ART start was quite small, from 6-12 weeks, so we didn’t really have enough spread in the data to enable us to draw solid conclusions,” she said at the annual Conference on Retroviruses & Opportunistic Infections.

The CHER trial compared South African infants with HIV on either 40 or 96 weeks of immediate ART with those on deferred ART. The results showed that early time-limited ART was associated with better clinical and immunologic outcomes than was deferred ART and influenced a change in treatment guidelines (Lancet 2013 Nov 9;382[9904]:1555-63).

In the current analysis, investigators examined viral control after treatment interruption in early-treated children and looked for factors that could influence time to viral rebound after ART cessation.

They measured viral load from stored samples at 1.8 weeks after ART interruption and then every 12 weeks thereafter. They defined viral rebound as two consecutive samples with 400 or more copies/mL.

Of the 183 children in the sample, 177 had a rebound; the remaining six children were censored from the analysis, five because they had restarted ART, and one child who remained in viral suppression with an undetectable viral load and was asymptomatic for 8.5 years off ART.

 

The estimated cumulative probability of rebound was 70% at 2 months following ART interruption, 80% at 4 months, 94% at 6 months, and 99% at 8 months.

In multivariable analysis, factors significantly associated with longer time to viral rebound included higher baseline CD4 counts (P = .03), higher birth weight (P = .032), and viral suppression within 40 weeks of starting on ART (P = .028)

In contrast, there were no significant associations with other factors in the multivariate model, including sex, baseline viral load, baseline CD8 percentage, HIV stage, status of therapy to prevent mother-to-child transmission, age at ART initiation, length of therapy, or treatment center.

Sensitivity analyses of a few cases in which there was a 4-7 month gap between rebound and the last viral load below 400 copies/mL before rebound showed similar results, Dr. Chan noted.

 

The study was the U.S. National Institutes of Health. Dr. Chan reported having nothing to disclose.

SOURCE: Violari A et al. CROI 2018, Abstract 137

 

BOSTON – For infants with HIV infection, baseline immune function and birth health appear to influence viral control after the discontinuation of antiretroviral therapy (ART), an analysis of data from the landmark CHER trial shows.

Among 183 children diagnosed with HIV between 6 and 12 weeks of age who were started on early, time-limited ART, longer time to viral rebound after treatment discontinuation was associated with higher baseline CD4 percentages, higher birth weight, and with achievement of viral suppression within 40 weeks of starting on ART, reported Man Chan, PhD, of the Medical Research Council clinical trials unit at University College London.

patrisyu/Thinkstock

“On the other hand, we did not find an association between age at ART start and length of therapy with a longer time to rebound. However, we should interpret these results with some caution, obviously because the range of ages at ART start was quite small, from 6-12 weeks, so we didn’t really have enough spread in the data to enable us to draw solid conclusions,” she said at the annual Conference on Retroviruses & Opportunistic Infections.

The CHER trial compared South African infants with HIV on either 40 or 96 weeks of immediate ART with those on deferred ART. The results showed that early time-limited ART was associated with better clinical and immunologic outcomes than was deferred ART and influenced a change in treatment guidelines (Lancet 2013 Nov 9;382[9904]:1555-63).

In the current analysis, investigators examined viral control after treatment interruption in early-treated children and looked for factors that could influence time to viral rebound after ART cessation.

They measured viral load from stored samples at 1.8 weeks after ART interruption and then every 12 weeks thereafter. They defined viral rebound as two consecutive samples with 400 or more copies/mL.

Of the 183 children in the sample, 177 had a rebound; the remaining six children were censored from the analysis, five because they had restarted ART, and one child who remained in viral suppression with an undetectable viral load and was asymptomatic for 8.5 years off ART.

 

The estimated cumulative probability of rebound was 70% at 2 months following ART interruption, 80% at 4 months, 94% at 6 months, and 99% at 8 months.

In multivariable analysis, factors significantly associated with longer time to viral rebound included higher baseline CD4 counts (P = .03), higher birth weight (P = .032), and viral suppression within 40 weeks of starting on ART (P = .028)

In contrast, there were no significant associations with other factors in the multivariate model, including sex, baseline viral load, baseline CD8 percentage, HIV stage, status of therapy to prevent mother-to-child transmission, age at ART initiation, length of therapy, or treatment center.

Sensitivity analyses of a few cases in which there was a 4-7 month gap between rebound and the last viral load below 400 copies/mL before rebound showed similar results, Dr. Chan noted.

 

The study was the U.S. National Institutes of Health. Dr. Chan reported having nothing to disclose.

SOURCE: Violari A et al. CROI 2018, Abstract 137

 

BOSTON – In persons infected with HIV-1, with or without hepatitis C coinfections, specific circulating microRNAs may signal the presence of liver injury and progression, investigators stated.

An analysis of small RNA expression in plasma samples from 144 HIV-infected patients showed that two microRNAs (miRNAs) in the same family of RNA fragments were significantly upregulated in patients with HIV-1 and HCV coinfections that progressed to liver cirrhosis, despite the patients having no evidence of liver fibrosis at the time of plasma sampling, reported Miguel Angel Martinez, PhD, of IrsiCaixa AIDS Research Institute in Badalona, Spain.

“Our results reveal that HIV-1 infection impacts liver miRNA metabolism and upregulated plasma levels of miRNAs that were previously associated with liver damage, even in the absence of an HCV coinfection,” he said at the Conference on Retroviruses & Opportunistic Infections. He reported the results in a themed discussion and scientific poster session.

Dr. Martinez and his colleagues performed large-scale deep sequencing analyses of miRNAs in plasma from 144 patients with HIV-1 who had elevated alanine aminotransferase (ALT), focal nodular hyperplasia, or HCV coinfections, and compared results with those from healthy blood donors and HCV mono-infected persons.

They identified 1,425 different mature miRNAs in the study samples. Compared with healthy donors, patients with HIV infections showed significantly dysregulated expression of 25 miRNAs, and 19 of these miRNAs were also found in patients with HCV monoinfection. All but 1 of 14 upregulated miRNAs in patients with HCV monoinfections were also upregulated in patients with HIV monoinfections.

Of these 13 upregulated miRNAs, 11 significantly and positively correlated with ALT and aspartate aminotransferase (AST) levels in most of the study samples, including those from healthy donors, Dr. Martinez noted.

“These results indicate that HIV mono-infection is able to dysregulate microRNAs related with liver injury and damage,” he said.

 

Of the 13 miRNAs, two, labeled miR-99a-5p and miR-100-5p, which belong to the same family of miRNAs, were found to be significantly upregulated in patients with HIV and HCV coinfections that later progressed to liver cirrhosis “even those these patients exhibited no liver fibrosis at the time of sampling,” he said

The two culprit miRNAs were significantly correlated with ALT and AST levels, as well as the degree of liver fibrosis.

A comparison of samples from patients with HIV monoinfection who had elevated ALT or focal nodular hyperplasia with those of patients with HIV infection but normal ALT levels showed that two other miRNAs, miR-122-3p and miR-193b-5p, were highly and significantly upregulated, and correlated with both aminotransferase and liver fibrosis levels.

“This study demonstrates the potential of microRNAs as biomarkers of liver injury progression in HIV-1 infected patients,” Dr. Martinez concluded.

The Spanish Instituto de Salud Carlos III and the Spanish AIDS network funded the study. Dr. Martinez reported having no conflicts of interest.

 

SOURCE: Martinez MA et al. CROI 2018, abstract 639.

 

BOSTON – In persons infected with HIV-1, with or without hepatitis C coinfections, specific circulating microRNAs may signal the presence of liver injury and progression, investigators stated.

An analysis of small RNA expression in plasma samples from 144 HIV-infected patients showed that two microRNAs (miRNAs) in the same family of RNA fragments were significantly upregulated in patients with HIV-1 and HCV coinfections that progressed to liver cirrhosis, despite the patients having no evidence of liver fibrosis at the time of plasma sampling, reported Miguel Angel Martinez, PhD, of IrsiCaixa AIDS Research Institute in Badalona, Spain.

“Our results reveal that HIV-1 infection impacts liver miRNA metabolism and upregulated plasma levels of miRNAs that were previously associated with liver damage, even in the absence of an HCV coinfection,” he said at the Conference on Retroviruses & Opportunistic Infections. He reported the results in a themed discussion and scientific poster session.

Dr. Martinez and his colleagues performed large-scale deep sequencing analyses of miRNAs in plasma from 144 patients with HIV-1 who had elevated alanine aminotransferase (ALT), focal nodular hyperplasia, or HCV coinfections, and compared results with those from healthy blood donors and HCV mono-infected persons.

They identified 1,425 different mature miRNAs in the study samples. Compared with healthy donors, patients with HIV infections showed significantly dysregulated expression of 25 miRNAs, and 19 of these miRNAs were also found in patients with HCV monoinfection. All but 1 of 14 upregulated miRNAs in patients with HCV monoinfections were also upregulated in patients with HIV monoinfections.

Of these 13 upregulated miRNAs, 11 significantly and positively correlated with ALT and aspartate aminotransferase (AST) levels in most of the study samples, including those from healthy donors, Dr. Martinez noted.

“These results indicate that HIV mono-infection is able to dysregulate microRNAs related with liver injury and damage,” he said.

 

Of the 13 miRNAs, two, labeled miR-99a-5p and miR-100-5p, which belong to the same family of miRNAs, were found to be significantly upregulated in patients with HIV and HCV coinfections that later progressed to liver cirrhosis “even those these patients exhibited no liver fibrosis at the time of sampling,” he said

The two culprit miRNAs were significantly correlated with ALT and AST levels, as well as the degree of liver fibrosis.

A comparison of samples from patients with HIV monoinfection who had elevated ALT or focal nodular hyperplasia with those of patients with HIV infection but normal ALT levels showed that two other miRNAs, miR-122-3p and miR-193b-5p, were highly and significantly upregulated, and correlated with both aminotransferase and liver fibrosis levels.

“This study demonstrates the potential of microRNAs as biomarkers of liver injury progression in HIV-1 infected patients,” Dr. Martinez concluded.

The Spanish Instituto de Salud Carlos III and the Spanish AIDS network funded the study. Dr. Martinez reported having no conflicts of interest.

 

SOURCE: Martinez MA et al. CROI 2018, abstract 639.

 

BOSTON – In persons infected with HIV-1, with or without hepatitis C coinfections, specific circulating microRNAs may signal the presence of liver injury and progression, investigators stated.

An analysis of small RNA expression in plasma samples from 144 HIV-infected patients showed that two microRNAs (miRNAs) in the same family of RNA fragments were significantly upregulated in patients with HIV-1 and HCV coinfections that progressed to liver cirrhosis, despite the patients having no evidence of liver fibrosis at the time of plasma sampling, reported Miguel Angel Martinez, PhD, of IrsiCaixa AIDS Research Institute in Badalona, Spain.

“Our results reveal that HIV-1 infection impacts liver miRNA metabolism and upregulated plasma levels of miRNAs that were previously associated with liver damage, even in the absence of an HCV coinfection,” he said at the Conference on Retroviruses & Opportunistic Infections. He reported the results in a themed discussion and scientific poster session.

Dr. Martinez and his colleagues performed large-scale deep sequencing analyses of miRNAs in plasma from 144 patients with HIV-1 who had elevated alanine aminotransferase (ALT), focal nodular hyperplasia, or HCV coinfections, and compared results with those from healthy blood donors and HCV mono-infected persons.

They identified 1,425 different mature miRNAs in the study samples. Compared with healthy donors, patients with HIV infections showed significantly dysregulated expression of 25 miRNAs, and 19 of these miRNAs were also found in patients with HCV monoinfection. All but 1 of 14 upregulated miRNAs in patients with HCV monoinfections were also upregulated in patients with HIV monoinfections.

Of these 13 upregulated miRNAs, 11 significantly and positively correlated with ALT and aspartate aminotransferase (AST) levels in most of the study samples, including those from healthy donors, Dr. Martinez noted.

“These results indicate that HIV mono-infection is able to dysregulate microRNAs related with liver injury and damage,” he said.

 

Of the 13 miRNAs, two, labeled miR-99a-5p and miR-100-5p, which belong to the same family of miRNAs, were found to be significantly upregulated in patients with HIV and HCV coinfections that later progressed to liver cirrhosis “even those these patients exhibited no liver fibrosis at the time of sampling,” he said

The two culprit miRNAs were significantly correlated with ALT and AST levels, as well as the degree of liver fibrosis.

A comparison of samples from patients with HIV monoinfection who had elevated ALT or focal nodular hyperplasia with those of patients with HIV infection but normal ALT levels showed that two other miRNAs, miR-122-3p and miR-193b-5p, were highly and significantly upregulated, and correlated with both aminotransferase and liver fibrosis levels.

“This study demonstrates the potential of microRNAs as biomarkers of liver injury progression in HIV-1 infected patients,” Dr. Martinez concluded.

The Spanish Instituto de Salud Carlos III and the Spanish AIDS network funded the study. Dr. Martinez reported having no conflicts of interest.

 

SOURCE: Martinez MA et al. CROI 2018, abstract 639.

 

BOSTON – World Health Organization guidelines on the use of isoniazid to prevent tuberculosis in HIV-infected women during pregnancy may need to be reconsidered in light of new evidence that isoniazid preventive therapy (IPT) is associated with a high risk for adverse pregnancy events, investigators say.

Among 156 HIV-infected pregnant women, the rate of adverse pregnancy outcomes was 23% for those randomly assigned to immediate IPT during pregnancy versus 17% for women randomized to IPT that was delayed until 12 weeks postpartum, a significant difference (P = .009), reported Amita Gupta, MD, from Johns Hopkins University in Baltimore.

KatarzynaBialasiewicz/thinkstockphotos

“These pregnancy outcomes included in utero demise – stillbirth – and low birth weight – less than 2500 grams,” she said at the annual Conference on Retroviruses and Opportunistic Infections.

There were six maternal deaths: two in the immediate therapy arm and four in the delayed arm. Two of the deaths were related to isoniazid-induced liver failure, and two other instances of liver failure were from other causes. The two remaining deaths were deemed unrelated to isoniazid: One woman died from bacterial sepsis, and the other from pneumonia.

The incidence of TB infections was low in both study arms, Dr. Gupta noted.

“So should we really be prioritizing IPT in pregnancy or give women the choice to know what the facts are and to select if they feel that they want to take on IPT during pregnancy or defer it until after they deliver?” she said at a briefing following her presentation of the data in an oral abstract session.

WHO guidelines for management of latent tuberculosis infections state that “[a]s isoniazid and rifampicin, the drugs commonly used in preventive treatment, are safe for use in pregnant women, pregnancy should not disqualify women living with HIV from receiving preventive treatment. Nevertheless, sound clinical judgment is required to determine the best time to provide it.”

 

However, the quality of evidence to support that statement is weak, primarily because pregnant women were typically excluded from IPT or other tuberculosis-prevention trials. In addition, isoniazid has been associated in retrospective studies with increased hepatotoxicity in women both during pregnancy and in the postpartum period, Dr. Gupta pointed out.

She and her colleagues conducted the phase 4 IMPAACT P1078 trial to test the hypothesis that IPT can be initiated safely during pregnancy. The study was conducted at centers in Botswana, Haiti, India, South Africa, Tanzania, Thailand, Uganda, and Zimbabwe.

HIV-infected pregnant women from 14 through 34 weeks of gestation who live in a high TB burden area (prevalence of 60 cases or more per 100,000 population) but had no evidence of TB infection were randomly assigned on a 1:1 basis to receive either immediate therapy with isoniazid 300 mg daily for 28 weeks, followed by placebo, or to the same dose of isoniazid started 12 weeks postpartum for 28 weeks. All patients also received vitamin B6 and a prenatal multivitamin until 40 weeks postpartum.

The participants were stratified by gestational age (14 to less than 24 weeks and 24 through 34 weeks). Women were excluded if they were suspected of having active TB, reported recent exposure, or had received TB treatment for more than 30 days in the past year. Women with recent acute hepatitis or peripheral neuropathy were excluded.

 

All women and their infants received the local standard of care for HIV. The investigators performed intensified TB case finding by using the WHO symptoms screening and exam, monitoring of signs and symptoms, conducting liver function tests, and screening for peripheral neuropathy.

“We had higher than expected adverse events in the study, but there was no statistical difference between arms,” she said.

In an intention-to-treat analysis, the rate of first maternal treatment-related grade 3 or greater adverse event or permanent drug discontinuation caused by toxicity (the primary endpoint) was 15.5% in the immediate IPT arm and 15.2% in the delayed IPT arm, a nonsignificant difference. The immediate therapy arm approached but did not quite reach the prespecified boundary of noninferiority, Dr. Gupta noted.

The per-protocol analysis of the primary endpoint was similar, at 17.6% vs. 17.8%, respectively.

 

In the intention-to-treat analysis, any-cause grade 3 or greater maternal adverse events were seen in 30.5% of women in the immediate arm versus 28.4% in the delayed arm, with an incidence-rate difference of 4.2 per 100 person-years, which did not reach the noninferiority boundary.

The respective rates in the per-protocol analysis were 33% vs. 30.4%, for an incidence-rate difference of 4.3 per 100 person-years.

In both groups, elevated liver enzymes and weight loss were the most common maternal adverse events.

All cause hepatotoxicity occurred in 6% of participants in the immediate arm and 7% in the deferred. Rates of permanent discontinuation because of toxicity were 4% and 6%, respectively, along with the two women in the immediate IPT arm and four in the delayed arm who died during the study. There were no significant differences in these outcomes between the groups.

 

Dr. Gupta noted that higher liver function test results were seen after delivery, regardless of whether the women were on IPT or what type of antiretroviral therapy they were receiving.

There were no significant differences seen in infant safety by treatment arm, a secondary endpoint.

“What did we learn? We learned that we had higher than expected adverse events that were at least possibly attributed to IPT in both arms. We did not reach our noninferiority margin partly because of the high rates, but we also did not find any major significant differences between the immediate and the deferred arm in terms of maternal safety when it was looked [at] by itself,” she said.

Although there were no significant differences in any maternal hepatotoxicity, grade 3 or greater infant adverse events, or maternal or infant death by treatment arm, “we did find an important distinction in terms of difference by adverse pregnancy outcomes, where immediate IPT was associated with more adverse pregnancy outcomes,” she said,

 

“I think we now need to reweigh the evidence for pros and cons for IPT in pregnancy,” Dr. Gupta concluded.

The study was sponsored the National Institutes of Health. Dr. Gupta reported having nothing to disclose.

SOURCE: Gupta A et al. CROI 2018, Abstract Number 142LB.

 

BOSTON – World Health Organization guidelines on the use of isoniazid to prevent tuberculosis in HIV-infected women during pregnancy may need to be reconsidered in light of new evidence that isoniazid preventive therapy (IPT) is associated with a high risk for adverse pregnancy events, investigators say.

Among 156 HIV-infected pregnant women, the rate of adverse pregnancy outcomes was 23% for those randomly assigned to immediate IPT during pregnancy versus 17% for women randomized to IPT that was delayed until 12 weeks postpartum, a significant difference (P = .009), reported Amita Gupta, MD, from Johns Hopkins University in Baltimore.

KatarzynaBialasiewicz/thinkstockphotos

“These pregnancy outcomes included in utero demise – stillbirth – and low birth weight – less than 2500 grams,” she said at the annual Conference on Retroviruses and Opportunistic Infections.

There were six maternal deaths: two in the immediate therapy arm and four in the delayed arm. Two of the deaths were related to isoniazid-induced liver failure, and two other instances of liver failure were from other causes. The two remaining deaths were deemed unrelated to isoniazid: One woman died from bacterial sepsis, and the other from pneumonia.

The incidence of TB infections was low in both study arms, Dr. Gupta noted.

“So should we really be prioritizing IPT in pregnancy or give women the choice to know what the facts are and to select if they feel that they want to take on IPT during pregnancy or defer it until after they deliver?” she said at a briefing following her presentation of the data in an oral abstract session.

WHO guidelines for management of latent tuberculosis infections state that “[a]s isoniazid and rifampicin, the drugs commonly used in preventive treatment, are safe for use in pregnant women, pregnancy should not disqualify women living with HIV from receiving preventive treatment. Nevertheless, sound clinical judgment is required to determine the best time to provide it.”

 

However, the quality of evidence to support that statement is weak, primarily because pregnant women were typically excluded from IPT or other tuberculosis-prevention trials. In addition, isoniazid has been associated in retrospective studies with increased hepatotoxicity in women both during pregnancy and in the postpartum period, Dr. Gupta pointed out.

She and her colleagues conducted the phase 4 IMPAACT P1078 trial to test the hypothesis that IPT can be initiated safely during pregnancy. The study was conducted at centers in Botswana, Haiti, India, South Africa, Tanzania, Thailand, Uganda, and Zimbabwe.

HIV-infected pregnant women from 14 through 34 weeks of gestation who live in a high TB burden area (prevalence of 60 cases or more per 100,000 population) but had no evidence of TB infection were randomly assigned on a 1:1 basis to receive either immediate therapy with isoniazid 300 mg daily for 28 weeks, followed by placebo, or to the same dose of isoniazid started 12 weeks postpartum for 28 weeks. All patients also received vitamin B6 and a prenatal multivitamin until 40 weeks postpartum.

The participants were stratified by gestational age (14 to less than 24 weeks and 24 through 34 weeks). Women were excluded if they were suspected of having active TB, reported recent exposure, or had received TB treatment for more than 30 days in the past year. Women with recent acute hepatitis or peripheral neuropathy were excluded.

 

All women and their infants received the local standard of care for HIV. The investigators performed intensified TB case finding by using the WHO symptoms screening and exam, monitoring of signs and symptoms, conducting liver function tests, and screening for peripheral neuropathy.

“We had higher than expected adverse events in the study, but there was no statistical difference between arms,” she said.

In an intention-to-treat analysis, the rate of first maternal treatment-related grade 3 or greater adverse event or permanent drug discontinuation caused by toxicity (the primary endpoint) was 15.5% in the immediate IPT arm and 15.2% in the delayed IPT arm, a nonsignificant difference. The immediate therapy arm approached but did not quite reach the prespecified boundary of noninferiority, Dr. Gupta noted.

The per-protocol analysis of the primary endpoint was similar, at 17.6% vs. 17.8%, respectively.

 

In the intention-to-treat analysis, any-cause grade 3 or greater maternal adverse events were seen in 30.5% of women in the immediate arm versus 28.4% in the delayed arm, with an incidence-rate difference of 4.2 per 100 person-years, which did not reach the noninferiority boundary.

The respective rates in the per-protocol analysis were 33% vs. 30.4%, for an incidence-rate difference of 4.3 per 100 person-years.

In both groups, elevated liver enzymes and weight loss were the most common maternal adverse events.

All cause hepatotoxicity occurred in 6% of participants in the immediate arm and 7% in the deferred. Rates of permanent discontinuation because of toxicity were 4% and 6%, respectively, along with the two women in the immediate IPT arm and four in the delayed arm who died during the study. There were no significant differences in these outcomes between the groups.

 

Dr. Gupta noted that higher liver function test results were seen after delivery, regardless of whether the women were on IPT or what type of antiretroviral therapy they were receiving.

There were no significant differences seen in infant safety by treatment arm, a secondary endpoint.

“What did we learn? We learned that we had higher than expected adverse events that were at least possibly attributed to IPT in both arms. We did not reach our noninferiority margin partly because of the high rates, but we also did not find any major significant differences between the immediate and the deferred arm in terms of maternal safety when it was looked [at] by itself,” she said.

Although there were no significant differences in any maternal hepatotoxicity, grade 3 or greater infant adverse events, or maternal or infant death by treatment arm, “we did find an important distinction in terms of difference by adverse pregnancy outcomes, where immediate IPT was associated with more adverse pregnancy outcomes,” she said,

 

“I think we now need to reweigh the evidence for pros and cons for IPT in pregnancy,” Dr. Gupta concluded.

The study was sponsored the National Institutes of Health. Dr. Gupta reported having nothing to disclose.

SOURCE: Gupta A et al. CROI 2018, Abstract Number 142LB.

 

BOSTON – World Health Organization guidelines on the use of isoniazid to prevent tuberculosis in HIV-infected women during pregnancy may need to be reconsidered in light of new evidence that isoniazid preventive therapy (IPT) is associated with a high risk for adverse pregnancy events, investigators say.

Among 156 HIV-infected pregnant women, the rate of adverse pregnancy outcomes was 23% for those randomly assigned to immediate IPT during pregnancy versus 17% for women randomized to IPT that was delayed until 12 weeks postpartum, a significant difference (P = .009), reported Amita Gupta, MD, from Johns Hopkins University in Baltimore.

KatarzynaBialasiewicz/thinkstockphotos

“These pregnancy outcomes included in utero demise – stillbirth – and low birth weight – less than 2500 grams,” she said at the annual Conference on Retroviruses and Opportunistic Infections.

There were six maternal deaths: two in the immediate therapy arm and four in the delayed arm. Two of the deaths were related to isoniazid-induced liver failure, and two other instances of liver failure were from other causes. The two remaining deaths were deemed unrelated to isoniazid: One woman died from bacterial sepsis, and the other from pneumonia.

The incidence of TB infections was low in both study arms, Dr. Gupta noted.

“So should we really be prioritizing IPT in pregnancy or give women the choice to know what the facts are and to select if they feel that they want to take on IPT during pregnancy or defer it until after they deliver?” she said at a briefing following her presentation of the data in an oral abstract session.

WHO guidelines for management of latent tuberculosis infections state that “[a]s isoniazid and rifampicin, the drugs commonly used in preventive treatment, are safe for use in pregnant women, pregnancy should not disqualify women living with HIV from receiving preventive treatment. Nevertheless, sound clinical judgment is required to determine the best time to provide it.”

 

However, the quality of evidence to support that statement is weak, primarily because pregnant women were typically excluded from IPT or other tuberculosis-prevention trials. In addition, isoniazid has been associated in retrospective studies with increased hepatotoxicity in women both during pregnancy and in the postpartum period, Dr. Gupta pointed out.

She and her colleagues conducted the phase 4 IMPAACT P1078 trial to test the hypothesis that IPT can be initiated safely during pregnancy. The study was conducted at centers in Botswana, Haiti, India, South Africa, Tanzania, Thailand, Uganda, and Zimbabwe.

HIV-infected pregnant women from 14 through 34 weeks of gestation who live in a high TB burden area (prevalence of 60 cases or more per 100,000 population) but had no evidence of TB infection were randomly assigned on a 1:1 basis to receive either immediate therapy with isoniazid 300 mg daily for 28 weeks, followed by placebo, or to the same dose of isoniazid started 12 weeks postpartum for 28 weeks. All patients also received vitamin B6 and a prenatal multivitamin until 40 weeks postpartum.

The participants were stratified by gestational age (14 to less than 24 weeks and 24 through 34 weeks). Women were excluded if they were suspected of having active TB, reported recent exposure, or had received TB treatment for more than 30 days in the past year. Women with recent acute hepatitis or peripheral neuropathy were excluded.

 

All women and their infants received the local standard of care for HIV. The investigators performed intensified TB case finding by using the WHO symptoms screening and exam, monitoring of signs and symptoms, conducting liver function tests, and screening for peripheral neuropathy.

“We had higher than expected adverse events in the study, but there was no statistical difference between arms,” she said.

In an intention-to-treat analysis, the rate of first maternal treatment-related grade 3 or greater adverse event or permanent drug discontinuation caused by toxicity (the primary endpoint) was 15.5% in the immediate IPT arm and 15.2% in the delayed IPT arm, a nonsignificant difference. The immediate therapy arm approached but did not quite reach the prespecified boundary of noninferiority, Dr. Gupta noted.

The per-protocol analysis of the primary endpoint was similar, at 17.6% vs. 17.8%, respectively.

 

In the intention-to-treat analysis, any-cause grade 3 or greater maternal adverse events were seen in 30.5% of women in the immediate arm versus 28.4% in the delayed arm, with an incidence-rate difference of 4.2 per 100 person-years, which did not reach the noninferiority boundary.

The respective rates in the per-protocol analysis were 33% vs. 30.4%, for an incidence-rate difference of 4.3 per 100 person-years.

In both groups, elevated liver enzymes and weight loss were the most common maternal adverse events.

All cause hepatotoxicity occurred in 6% of participants in the immediate arm and 7% in the deferred. Rates of permanent discontinuation because of toxicity were 4% and 6%, respectively, along with the two women in the immediate IPT arm and four in the delayed arm who died during the study. There were no significant differences in these outcomes between the groups.

 

Dr. Gupta noted that higher liver function test results were seen after delivery, regardless of whether the women were on IPT or what type of antiretroviral therapy they were receiving.

There were no significant differences seen in infant safety by treatment arm, a secondary endpoint.

“What did we learn? We learned that we had higher than expected adverse events that were at least possibly attributed to IPT in both arms. We did not reach our noninferiority margin partly because of the high rates, but we also did not find any major significant differences between the immediate and the deferred arm in terms of maternal safety when it was looked [at] by itself,” she said.

Although there were no significant differences in any maternal hepatotoxicity, grade 3 or greater infant adverse events, or maternal or infant death by treatment arm, “we did find an important distinction in terms of difference by adverse pregnancy outcomes, where immediate IPT was associated with more adverse pregnancy outcomes,” she said,

 

“I think we now need to reweigh the evidence for pros and cons for IPT in pregnancy,” Dr. Gupta concluded.

The study was sponsored the National Institutes of Health. Dr. Gupta reported having nothing to disclose.

SOURCE: Gupta A et al. CROI 2018, Abstract Number 142LB.

 

BOSTON – Efavirenz-based antiretroviral therapy may significantly impair the effectiveness of vaginal ring contraceptives, investigators reported.

Over a 21-day period, levels of estrogen among women who used a vaginal ring (NuvaRing) while on efavirenz-based antiretroviral therapy (ART) were up to 79% lower, and levels of progestin were up to 57% lower, than in women with HIV infection who used the vaginal ring before starting ART, reported Kimberly K. Scarsi, PharmD, of the University of Nebraska, Omaha.

In contrast, women on an atazanavir-based ART regimen had lower estrogen levels than untreated controls who used a vaginal ring, but higher levels of progestin – the primary antiovulatory component of the ring – suggesting that it would retain contraceptive effectiveness, she said at the annual Conference on Retroviruses and Opportunistic Infections.

“In a broader context, these data can be applied to other drugs that behave similarly. So for example, erythromycins are also known to interfere with hormones in this way, as well as some anticonvulsant agents that may also impair the effectiveness of vaginal ring contraceptives,” she said at a brief, following her presentation of the data in an oral abstract session.

 

She noted that the findings have important implications for developers of vaginal rings designed to prevent HIV transmission as well as provide hormone-based contraception.

Dr. Scarsi and colleagues conducted a phase 2, international, nonrandomized, parallel pharmacokinetic study comparing levels of estrogen in the form of ethinyl estradiol (EE) and progestin in the form of etonogestrel among women with HIV infection who had not yet begun ART, as well as women on efavirenz- or atazanavir-based regimens.

Participants 16 years and older from centers in Africa, Asia, and North and South America were enrolled. The patients had to be willing to use a second, nonhormonal form of effective contraceptive, and if they were not on ART had to have CD4 cell counts of 350 cells/m³ or higher at screening. Participants on ART had to be on stable therapy for at least 30 days, and have HIV-1 RNA of 400 copies/mL or less.

A total of 25 control subjects, 25 women on efavirenz, and 24 on atazanavir were available for the primary pharmacokinetic analysis.

 

Over 21 days, EE levels among the efavirenz groups were 53%-57% lower than those of controls. Levels among the atazanavir groups were 29%-59% lower.

On days 7, 14, and 21, the EE geometric means ratios in efavirenz-treated patients versus controls were 0.47, 0.45, and 0.43, respectively (P less than .05 for each comparison).

In the atazanavir group, the EE geometric mean ratios versus controls at the same time points were 0.68 (P nonsignificant), 0.71 (P less than .05), and 0.65 (P less than .05).

For those in the efavirenz group, etonogestrel levels over 21 days were 76%-79% lower than in controls. In contrast, levels in the atazanavir group were 71%-79% higher than in controls.

The geometric mean ratios for the efavirenz group at 7, 14, and 21 days versus controls were 0.21, 0.22, and 0.24 (P less than .05 for all comparisons). In the atazanavir group, the respective geometric mean ratios were 1.71, 1.79, and 1.74 (P less than .05 for all comparisons).

 

Safety and tolerability of the ring, a secondary endpoint, was similar among the groups, with slightly more than one-fourth of participants in each arm having a mild adverse event, most commonly associated with abnormal vaginal discharge or menstrual irregularities such as spotting.

The investigators also looked at endogenous progesterone levels as a surrogate for ovulation. Although the ring’s package insert recommends to start using it within the first 5 days after the start of menses, the median enrollment time was 9 days after menses in all groups. Nonetheless, all participants in the control and atazanavir groups had undetectable progesterone values (less than 5 ng/mL) by day 14.

In contrast, among women in the efavirenz group, all women had undetectable progesterone values only at day 21.

The findings suggest that, when considering contraception and ART in HIV-infected women, developers of intravaginally administered drugs should consider systemic drug-drug interactions, because hormones released from a vaginal ring are extensively absorbed and act systemically. It is also important to consider local drug-drug interactions with the microbiome, because although it is known that dapivirine released from a vaginal ring can concentrate in the vaginal tract, possible interactions with the local microbiome, local drug transporters, and local drug-metabolizing enzymes are not known, Dr. Scarsi cautioned.

The study was supported by the National Institutes of Health. Merck provided the vaginal ring used in the study. Dr. Scarsi reported having no conflicts of interest to disclose.

 

SOURCE: Scarsi KK et al. CROI 2018, Abstract 141.

 

BOSTON – Efavirenz-based antiretroviral therapy may significantly impair the effectiveness of vaginal ring contraceptives, investigators reported.

Over a 21-day period, levels of estrogen among women who used a vaginal ring (NuvaRing) while on efavirenz-based antiretroviral therapy (ART) were up to 79% lower, and levels of progestin were up to 57% lower, than in women with HIV infection who used the vaginal ring before starting ART, reported Kimberly K. Scarsi, PharmD, of the University of Nebraska, Omaha.

In contrast, women on an atazanavir-based ART regimen had lower estrogen levels than untreated controls who used a vaginal ring, but higher levels of progestin – the primary antiovulatory component of the ring – suggesting that it would retain contraceptive effectiveness, she said at the annual Conference on Retroviruses and Opportunistic Infections.

“In a broader context, these data can be applied to other drugs that behave similarly. So for example, erythromycins are also known to interfere with hormones in this way, as well as some anticonvulsant agents that may also impair the effectiveness of vaginal ring contraceptives,” she said at a brief, following her presentation of the data in an oral abstract session.

 

She noted that the findings have important implications for developers of vaginal rings designed to prevent HIV transmission as well as provide hormone-based contraception.

Dr. Scarsi and colleagues conducted a phase 2, international, nonrandomized, parallel pharmacokinetic study comparing levels of estrogen in the form of ethinyl estradiol (EE) and progestin in the form of etonogestrel among women with HIV infection who had not yet begun ART, as well as women on efavirenz- or atazanavir-based regimens.

Participants 16 years and older from centers in Africa, Asia, and North and South America were enrolled. The patients had to be willing to use a second, nonhormonal form of effective contraceptive, and if they were not on ART had to have CD4 cell counts of 350 cells/m³ or higher at screening. Participants on ART had to be on stable therapy for at least 30 days, and have HIV-1 RNA of 400 copies/mL or less.

A total of 25 control subjects, 25 women on efavirenz, and 24 on atazanavir were available for the primary pharmacokinetic analysis.

 

Over 21 days, EE levels among the efavirenz groups were 53%-57% lower than those of controls. Levels among the atazanavir groups were 29%-59% lower.

On days 7, 14, and 21, the EE geometric means ratios in efavirenz-treated patients versus controls were 0.47, 0.45, and 0.43, respectively (P less than .05 for each comparison).

In the atazanavir group, the EE geometric mean ratios versus controls at the same time points were 0.68 (P nonsignificant), 0.71 (P less than .05), and 0.65 (P less than .05).

For those in the efavirenz group, etonogestrel levels over 21 days were 76%-79% lower than in controls. In contrast, levels in the atazanavir group were 71%-79% higher than in controls.

The geometric mean ratios for the efavirenz group at 7, 14, and 21 days versus controls were 0.21, 0.22, and 0.24 (P less than .05 for all comparisons). In the atazanavir group, the respective geometric mean ratios were 1.71, 1.79, and 1.74 (P less than .05 for all comparisons).

 

Safety and tolerability of the ring, a secondary endpoint, was similar among the groups, with slightly more than one-fourth of participants in each arm having a mild adverse event, most commonly associated with abnormal vaginal discharge or menstrual irregularities such as spotting.

The investigators also looked at endogenous progesterone levels as a surrogate for ovulation. Although the ring’s package insert recommends to start using it within the first 5 days after the start of menses, the median enrollment time was 9 days after menses in all groups. Nonetheless, all participants in the control and atazanavir groups had undetectable progesterone values (less than 5 ng/mL) by day 14.

In contrast, among women in the efavirenz group, all women had undetectable progesterone values only at day 21.

The findings suggest that, when considering contraception and ART in HIV-infected women, developers of intravaginally administered drugs should consider systemic drug-drug interactions, because hormones released from a vaginal ring are extensively absorbed and act systemically. It is also important to consider local drug-drug interactions with the microbiome, because although it is known that dapivirine released from a vaginal ring can concentrate in the vaginal tract, possible interactions with the local microbiome, local drug transporters, and local drug-metabolizing enzymes are not known, Dr. Scarsi cautioned.

The study was supported by the National Institutes of Health. Merck provided the vaginal ring used in the study. Dr. Scarsi reported having no conflicts of interest to disclose.

 

SOURCE: Scarsi KK et al. CROI 2018, Abstract 141.

 

BOSTON – Efavirenz-based antiretroviral therapy may significantly impair the effectiveness of vaginal ring contraceptives, investigators reported.

Over a 21-day period, levels of estrogen among women who used a vaginal ring (NuvaRing) while on efavirenz-based antiretroviral therapy (ART) were up to 79% lower, and levels of progestin were up to 57% lower, than in women with HIV infection who used the vaginal ring before starting ART, reported Kimberly K. Scarsi, PharmD, of the University of Nebraska, Omaha.

In contrast, women on an atazanavir-based ART regimen had lower estrogen levels than untreated controls who used a vaginal ring, but higher levels of progestin – the primary antiovulatory component of the ring – suggesting that it would retain contraceptive effectiveness, she said at the annual Conference on Retroviruses and Opportunistic Infections.

“In a broader context, these data can be applied to other drugs that behave similarly. So for example, erythromycins are also known to interfere with hormones in this way, as well as some anticonvulsant agents that may also impair the effectiveness of vaginal ring contraceptives,” she said at a brief, following her presentation of the data in an oral abstract session.

 

She noted that the findings have important implications for developers of vaginal rings designed to prevent HIV transmission as well as provide hormone-based contraception.

Dr. Scarsi and colleagues conducted a phase 2, international, nonrandomized, parallel pharmacokinetic study comparing levels of estrogen in the form of ethinyl estradiol (EE) and progestin in the form of etonogestrel among women with HIV infection who had not yet begun ART, as well as women on efavirenz- or atazanavir-based regimens.

Participants 16 years and older from centers in Africa, Asia, and North and South America were enrolled. The patients had to be willing to use a second, nonhormonal form of effective contraceptive, and if they were not on ART had to have CD4 cell counts of 350 cells/m³ or higher at screening. Participants on ART had to be on stable therapy for at least 30 days, and have HIV-1 RNA of 400 copies/mL or less.

A total of 25 control subjects, 25 women on efavirenz, and 24 on atazanavir were available for the primary pharmacokinetic analysis.

 

Over 21 days, EE levels among the efavirenz groups were 53%-57% lower than those of controls. Levels among the atazanavir groups were 29%-59% lower.

On days 7, 14, and 21, the EE geometric means ratios in efavirenz-treated patients versus controls were 0.47, 0.45, and 0.43, respectively (P less than .05 for each comparison).

In the atazanavir group, the EE geometric mean ratios versus controls at the same time points were 0.68 (P nonsignificant), 0.71 (P less than .05), and 0.65 (P less than .05).

For those in the efavirenz group, etonogestrel levels over 21 days were 76%-79% lower than in controls. In contrast, levels in the atazanavir group were 71%-79% higher than in controls.

The geometric mean ratios for the efavirenz group at 7, 14, and 21 days versus controls were 0.21, 0.22, and 0.24 (P less than .05 for all comparisons). In the atazanavir group, the respective geometric mean ratios were 1.71, 1.79, and 1.74 (P less than .05 for all comparisons).

 

Safety and tolerability of the ring, a secondary endpoint, was similar among the groups, with slightly more than one-fourth of participants in each arm having a mild adverse event, most commonly associated with abnormal vaginal discharge or menstrual irregularities such as spotting.

The investigators also looked at endogenous progesterone levels as a surrogate for ovulation. Although the ring’s package insert recommends to start using it within the first 5 days after the start of menses, the median enrollment time was 9 days after menses in all groups. Nonetheless, all participants in the control and atazanavir groups had undetectable progesterone values (less than 5 ng/mL) by day 14.

In contrast, among women in the efavirenz group, all women had undetectable progesterone values only at day 21.

The findings suggest that, when considering contraception and ART in HIV-infected women, developers of intravaginally administered drugs should consider systemic drug-drug interactions, because hormones released from a vaginal ring are extensively absorbed and act systemically. It is also important to consider local drug-drug interactions with the microbiome, because although it is known that dapivirine released from a vaginal ring can concentrate in the vaginal tract, possible interactions with the local microbiome, local drug transporters, and local drug-metabolizing enzymes are not known, Dr. Scarsi cautioned.

The study was supported by the National Institutes of Health. Merck provided the vaginal ring used in the study. Dr. Scarsi reported having no conflicts of interest to disclose.

 

SOURCE: Scarsi KK et al. CROI 2018, Abstract 141.

 

BOSTON – Bacterial pneumonia, herpes zoster, and thrombocytopenia in adults of any age could be signs of a possible undiagnosed HIV infection and should trigger HIV testing, investigators in a study of aging veterans contend.

Among adults younger than age 60 years, findings of anemia and/or lymphocytopenia also should trigger HIV testing, said Amy C. Justice, MD, PhD, from the Yale School of Public Health, New Haven, Conn.

Neil Osterweil/MDedge News

“Older people are more likely to present with advanced HIV and specific non-AIDS conditions. Convergence of HIV and aging-associated non-AIDS conditions contributes to delays in diagnosis,” she said at the annual Conference on Retroviruses and Opportunistic Infections.

There are sparse data on how older persons first present with HIV infections, but evidence from a cross-sectional study of 44,491 HIV-infected individuals in the North American AIDS Cohort Collaboration on Research and Design showed that adults aged 50 years and older have lower CD4 cell counts and more advanced HIV disease at the time of presentation.

 

To get a better sense of HIV infections among older patients, Dr. Justice and her colleagues in VACS (the Veterans Aging Cohort Study) asked if delays in diagnosis persisted, whether non-AIDS conditions differed from conditions seen in HIV uninfected persons of the same age, and whether selected age-associated non-AIDS conditions should be triggers for HIV testing.

They reviewed data on persons diagnosed with HIV from 2010 through 2015 within the Veterans healthcare system. They defined incidence HIV as detectable HIV-1 RNA prior to antiretroviral therapy, and matched infected to uninfected individuals by age, race, sex, site, and year.

They used diagnostic codes within 1 year before or 6 months after HIV diagnosis for data on AIDS-defining illnesses, bacterial pneumonia, and herpes zoster, and laboratory data within 6 months of diagnosis for CD4 counts, HIV-1 RNA, hemoglobin, platelet, and lymphocyte count.

In addition, the investigators drew on the Centers for Disease Control and Prevention HIV Surveillance Report for data on HIV prevalence among different age groups, and chart reviews from the Nathan Smith Clinic at Yale New Haven Hospital for clinical information.

 

The analysis compared incident HIV by age among the VACS, the Nathan Smith Clinic, and CDC data, and HIV severity by age in the VACS vs. Nathan Smith.

In the VACS, Nathan Smith, and CDC data sets, respectively, the percentages of individuals aged 50 years and older with newly diagnosed HIV were 48%, 24%, and 18%.

An analysis of severity of HIV at diagnosis showed that among individuals aged 60 years and older in the VACS cohort, 20% had an AIDS-defining illness, 43% had CD4 counts below 200/mL, and 49% were diagnosed with AIDS. In the Nathan Smith cohort, 33% had an AIDS-defining illness, 58% had CD counts below 200/mL, and 67% received an AIDS diagnosis.

Looking at non-AIDS–associated conditions, they found that the absolute risk for bacterial pneumonia for HIV-positive patients increased from 6.6% among those aged 40 years and younger to 13.7% for those aged 60 years and older. In contrast, the risk for pneumonia was just 1.2% among HIV-negative controls aged 40 years and younger, and grew only slightly to 2.1% for those aged 60 years and older. The relative risk for pneumonia among HIV-positive vs. negative individuals ranged from 5.3 among those younger than 40 years, to 6.4 among those aged 60 years and and older.

 

“In all cases, the probability of HIV, given a diagnosis of bacterial pneumonia, exceeds 1%, suggesting that anyone presenting with bacterial pneumonia should reasonably tested for HIV,” Dr. Justice said.

Similarly, the relative risks for herpes zoster for HIV-infected persons ranged from 22.3 in the youngest cohort members to 7.3 among the oldest, and the respective relative risks for thrombocytopenia ranged from 25 to 3.2, suggesting that these findings should trigger HIV testing, Dr. Justice said.

Differences between HIV-infected and uninfected persons with both anemia and lymphocytopenia are more pronounced for younger than for older patients, suggesting that these conditions should trigger HIV testing when they occur in those under age 60, Dr. Justice said.

The study was supported by grants from the National Institutes of Health and Veterans Health Administration. Dr. Justice reported having no disclosures.

SOURCE: Justice AC et al. 2018 CROI, Abstract 92

 

BOSTON – Bacterial pneumonia, herpes zoster, and thrombocytopenia in adults of any age could be signs of a possible undiagnosed HIV infection and should trigger HIV testing, investigators in a study of aging veterans contend.

Among adults younger than age 60 years, findings of anemia and/or lymphocytopenia also should trigger HIV testing, said Amy C. Justice, MD, PhD, from the Yale School of Public Health, New Haven, Conn.

Neil Osterweil/MDedge News

“Older people are more likely to present with advanced HIV and specific non-AIDS conditions. Convergence of HIV and aging-associated non-AIDS conditions contributes to delays in diagnosis,” she said at the annual Conference on Retroviruses and Opportunistic Infections.

There are sparse data on how older persons first present with HIV infections, but evidence from a cross-sectional study of 44,491 HIV-infected individuals in the North American AIDS Cohort Collaboration on Research and Design showed that adults aged 50 years and older have lower CD4 cell counts and more advanced HIV disease at the time of presentation.

 

To get a better sense of HIV infections among older patients, Dr. Justice and her colleagues in VACS (the Veterans Aging Cohort Study) asked if delays in diagnosis persisted, whether non-AIDS conditions differed from conditions seen in HIV uninfected persons of the same age, and whether selected age-associated non-AIDS conditions should be triggers for HIV testing.

They reviewed data on persons diagnosed with HIV from 2010 through 2015 within the Veterans healthcare system. They defined incidence HIV as detectable HIV-1 RNA prior to antiretroviral therapy, and matched infected to uninfected individuals by age, race, sex, site, and year.

They used diagnostic codes within 1 year before or 6 months after HIV diagnosis for data on AIDS-defining illnesses, bacterial pneumonia, and herpes zoster, and laboratory data within 6 months of diagnosis for CD4 counts, HIV-1 RNA, hemoglobin, platelet, and lymphocyte count.

In addition, the investigators drew on the Centers for Disease Control and Prevention HIV Surveillance Report for data on HIV prevalence among different age groups, and chart reviews from the Nathan Smith Clinic at Yale New Haven Hospital for clinical information.

 

The analysis compared incident HIV by age among the VACS, the Nathan Smith Clinic, and CDC data, and HIV severity by age in the VACS vs. Nathan Smith.

In the VACS, Nathan Smith, and CDC data sets, respectively, the percentages of individuals aged 50 years and older with newly diagnosed HIV were 48%, 24%, and 18%.

An analysis of severity of HIV at diagnosis showed that among individuals aged 60 years and older in the VACS cohort, 20% had an AIDS-defining illness, 43% had CD4 counts below 200/mL, and 49% were diagnosed with AIDS. In the Nathan Smith cohort, 33% had an AIDS-defining illness, 58% had CD counts below 200/mL, and 67% received an AIDS diagnosis.

Looking at non-AIDS–associated conditions, they found that the absolute risk for bacterial pneumonia for HIV-positive patients increased from 6.6% among those aged 40 years and younger to 13.7% for those aged 60 years and older. In contrast, the risk for pneumonia was just 1.2% among HIV-negative controls aged 40 years and younger, and grew only slightly to 2.1% for those aged 60 years and older. The relative risk for pneumonia among HIV-positive vs. negative individuals ranged from 5.3 among those younger than 40 years, to 6.4 among those aged 60 years and and older.

 

“In all cases, the probability of HIV, given a diagnosis of bacterial pneumonia, exceeds 1%, suggesting that anyone presenting with bacterial pneumonia should reasonably tested for HIV,” Dr. Justice said.

Similarly, the relative risks for herpes zoster for HIV-infected persons ranged from 22.3 in the youngest cohort members to 7.3 among the oldest, and the respective relative risks for thrombocytopenia ranged from 25 to 3.2, suggesting that these findings should trigger HIV testing, Dr. Justice said.

Differences between HIV-infected and uninfected persons with both anemia and lymphocytopenia are more pronounced for younger than for older patients, suggesting that these conditions should trigger HIV testing when they occur in those under age 60, Dr. Justice said.

The study was supported by grants from the National Institutes of Health and Veterans Health Administration. Dr. Justice reported having no disclosures.

SOURCE: Justice AC et al. 2018 CROI, Abstract 92

 

BOSTON – Bacterial pneumonia, herpes zoster, and thrombocytopenia in adults of any age could be signs of a possible undiagnosed HIV infection and should trigger HIV testing, investigators in a study of aging veterans contend.

Among adults younger than age 60 years, findings of anemia and/or lymphocytopenia also should trigger HIV testing, said Amy C. Justice, MD, PhD, from the Yale School of Public Health, New Haven, Conn.

Neil Osterweil/MDedge News

“Older people are more likely to present with advanced HIV and specific non-AIDS conditions. Convergence of HIV and aging-associated non-AIDS conditions contributes to delays in diagnosis,” she said at the annual Conference on Retroviruses and Opportunistic Infections.

There are sparse data on how older persons first present with HIV infections, but evidence from a cross-sectional study of 44,491 HIV-infected individuals in the North American AIDS Cohort Collaboration on Research and Design showed that adults aged 50 years and older have lower CD4 cell counts and more advanced HIV disease at the time of presentation.

 

To get a better sense of HIV infections among older patients, Dr. Justice and her colleagues in VACS (the Veterans Aging Cohort Study) asked if delays in diagnosis persisted, whether non-AIDS conditions differed from conditions seen in HIV uninfected persons of the same age, and whether selected age-associated non-AIDS conditions should be triggers for HIV testing.

They reviewed data on persons diagnosed with HIV from 2010 through 2015 within the Veterans healthcare system. They defined incidence HIV as detectable HIV-1 RNA prior to antiretroviral therapy, and matched infected to uninfected individuals by age, race, sex, site, and year.

They used diagnostic codes within 1 year before or 6 months after HIV diagnosis for data on AIDS-defining illnesses, bacterial pneumonia, and herpes zoster, and laboratory data within 6 months of diagnosis for CD4 counts, HIV-1 RNA, hemoglobin, platelet, and lymphocyte count.

In addition, the investigators drew on the Centers for Disease Control and Prevention HIV Surveillance Report for data on HIV prevalence among different age groups, and chart reviews from the Nathan Smith Clinic at Yale New Haven Hospital for clinical information.

 

The analysis compared incident HIV by age among the VACS, the Nathan Smith Clinic, and CDC data, and HIV severity by age in the VACS vs. Nathan Smith.

In the VACS, Nathan Smith, and CDC data sets, respectively, the percentages of individuals aged 50 years and older with newly diagnosed HIV were 48%, 24%, and 18%.

An analysis of severity of HIV at diagnosis showed that among individuals aged 60 years and older in the VACS cohort, 20% had an AIDS-defining illness, 43% had CD4 counts below 200/mL, and 49% were diagnosed with AIDS. In the Nathan Smith cohort, 33% had an AIDS-defining illness, 58% had CD counts below 200/mL, and 67% received an AIDS diagnosis.

Looking at non-AIDS–associated conditions, they found that the absolute risk for bacterial pneumonia for HIV-positive patients increased from 6.6% among those aged 40 years and younger to 13.7% for those aged 60 years and older. In contrast, the risk for pneumonia was just 1.2% among HIV-negative controls aged 40 years and younger, and grew only slightly to 2.1% for those aged 60 years and older. The relative risk for pneumonia among HIV-positive vs. negative individuals ranged from 5.3 among those younger than 40 years, to 6.4 among those aged 60 years and and older.

 

“In all cases, the probability of HIV, given a diagnosis of bacterial pneumonia, exceeds 1%, suggesting that anyone presenting with bacterial pneumonia should reasonably tested for HIV,” Dr. Justice said.

Similarly, the relative risks for herpes zoster for HIV-infected persons ranged from 22.3 in the youngest cohort members to 7.3 among the oldest, and the respective relative risks for thrombocytopenia ranged from 25 to 3.2, suggesting that these findings should trigger HIV testing, Dr. Justice said.

Differences between HIV-infected and uninfected persons with both anemia and lymphocytopenia are more pronounced for younger than for older patients, suggesting that these conditions should trigger HIV testing when they occur in those under age 60, Dr. Justice said.

The study was supported by grants from the National Institutes of Health and Veterans Health Administration. Dr. Justice reported having no disclosures.

SOURCE: Justice AC et al. 2018 CROI, Abstract 92