A look at some of the HIV drug and prevention strategies, and more presented at CROI 2018
By Enid Vázquez @ENIDVAZQUEZPA

There’s way more going on at CROI than we can report here. Go to croiconference.org for more reports, including these topics. Webcasts and poster presentations are available. For instance, sessions include:

  • Growing Up with HIV 
  • HIV-Exposed Infants: Are They Different and Why?
  • HIV in People Who Inject Drugs: An Evolving and Persistent Challenge
  • The Evolving HIV Epidemic in the United States (a call to action by Dr. Carlos del Rio of Emory University)
  • PrEP Works, Now What?

Also go to ifarablog.org for videotaped interviews with presenters (also found on YouTube).

Abstract 22

Switching to Biktarvy from Triumeq works well

 

Biktarvy is one of the newest HIV medications on the market, approved by the FDA earlier this year on February 7.

Dr. Jean-Michel Molina, of St. Louis Hospital in Paris, reported non-inferiority for switching from Triumeq to Biktarvy. Meaning that the results were basically the same—not better, not worse. Comparisons of older drugs to newer ones are important in case people need to switch.

Biktarvy and Triumeq are the only two integrase inhibitor-based single-tablet regimens that don’t include a booster drug. For this reason, patients can avoid a lot of drug interactions.

The integrase inhibitor dolutegravir in Triumeq (which is available by itself under the brand name Tivicay), is known for a high barrier to drug resistance. Biktarvy research, including this presentation, shows that its integrase inhibitor, bictegravir, seems to have just as high of a barrier to drug resistance.

Abstract 24

By a hair—proof of your drug levels

HIV treatment failure can be predicted by using drug levels found in hair samples.

“Hair antiretroviral (ARV) levels reflect long-term exposure and have been associated with virologic [viral load] outcomes in cohorts [groups of people], but have never been evaluated in a treatment trial,” the A5257 study team reported in its abstract (written report).

The AIDS Clinical Trials Group (ACTG) A5257 team took hair samples at weeks 4, 8, 16, and then quarterly thereafter.

Advantages to using hair samples over blood draws include long-term adherence measures vs. the shorter-term results found in plasma; ease and lower cost of collecting hair samples; and no need for refrigeration or biohazard precautions.

Samples were cut close to the scalp in the back of the head. Samples were not yanked out, because the hair root wasn’t needed, as it is when running a DNA test. Baldness rules out the use of hair samples, because eyebrows and other areas are not usable. Interestingly, some study participants declined to provide hair samples, however small, because they didn’t want to risk “ruining” their hairstyle, presenter Dr. Monica Gandhi reported in response to an audience member’s question about the acceptability of the haircutting.

Hair and viral load data from 599 study participants showed that those with the lowest drug levels in their hair samples had the highest risk of treatment failure. Those who had the lowest drug measurements (the bottom 33% of all participants) had a 1 in 4 (25%) risk of treatment failure at two years of therapy.

This compared to 6% risk of failure for people with measurements in the second tertile (between 34–66%) and 3% for those in the highest tertile of drug levels (67–100%).

“We show for the first time that higher long-term ARV exposure as assessed by hair levels predicted a significantly decreased risk of virologic failure (VF) in a randomized treatment trial,” the team concluded. “The risk of virologic failure was high following a low hair ARV level. Correlations between self-reported adherence and hair levels were poor, likely revealing limitations to self-report. Further study is warranted on whether early monitoring of hair ARV levels followed by targeted adherence interventions based on this metric will be able to reduce subsequent VF rates on HIV treatment.”

“As researchers are always looking for new ways to monitor adherence, having another tool in our kit could prove invaluable,” the ACTG noted.

Abstract 25

By a blood spot—proof of tenofovir drug levels

Blood was not to be outdone by a lousy hair.

“Tenofovir diphosphate in dried blood spots is a strong predictor of viral suppression,” reported Dr. Jose R. Castillo-Mancilla and team, from the University of Colorado Anschutz Medical Campus in Aurora and the Denver Health and Hospital Authority.

According to their study abstract, “Tenofovir diphosphate (TFV-DP) in dried blood spots (DBS) is a marker of cumulative tenofovir disoproxil fumarate (TDF) exposure and a predictor of PrEP efficacy. However, the predictive value of TFV-DP in HIV infection has not been evaluated.”

Tenofovir, which in different formulations is used in the majority of HIV drug regimens in the U.S., is not used alone, of course. Nevertheless, the team noted that use of dried blood spots for measuring the drug’s level is “a promising adherence tool in this population.”

The abstract’s conclusion noted that, “TFV-DP showed slight differences across subgroups. Additional research is required to assess the contributions of antiretroviral adherence versus biology/pharmacology on TFV-DP concentrations among these subgroups.”

More than 500 study participants donated the blood spots.

Late breaker 37LB

1 month of TB prevention non-inferior to 9 months

Good news: the use of one month’s preventive therapy for tuberculosis was found to be non-inferior to the standard nine months of prevention medicine.

“Tuberculosis (TB) is the leading killer of people with HIV infection [worldwide],” reported the ACTG A5279 study team. “Preventive therapy is effective but current regimens are limited by toxicity and low completion rates. We hypothesized that an ultra-short course of isoniazid (H)/rifapentine (P) would be non-inferior to 9 months H in people with HIV infection.”

It was. Furthermore, the ultra-short course of medicine was associated with fewer adverse events and a higher rate of completion.

Results are from 3,000 people living with HIV from 10 different countries.

Knudson (PHOTO BY LIZ HIGHLEYMAN)

Abstract 76,abstract and Poster 701

Heart disease

“We know that people living with HIV have higher rates of cardiovascular disease, but less is known about peripheral artery disease [PAD]—the narrowing of the veins in the legs,” reported Dr. Andreas Knudsen, of the Rigshospitalet in Copenhagen, Denmark, on behalf of a Copenhagen and London research team. “It can progress to pain and ulceration, and in time, even to gangrene and amputation.”

PAD was measured by taking the blood pressure in a leg and comparing it to blood pressure in an arm, called the ankle-brachial index (ABI).

The primary symptom of PAD was defined as pain on walking that eased when standing.

The team found that the risk of PAD was twice as high in study participants living with HIV compared to a control group of HIV-negative individuals.

Also, as the team had hypothesized, HIV itself was independently associated with PAD.

Participants included 908 patients from COCOMO (the Copenhagen Comorbidity in HIV Infection study). Dr. Knudsen was a winner of one of this year’s CROI Young Investigator awards.

According to the team’s abstract, “Peripheral artery disease (PAD) is a manifestation of CVD [cardiovascular disease] that is less well-explored in PLWH with conflicting reports on prevalence and risk factors. [ABI] is an excellent diagnostic tool for diagnosing PAD… Our findings expand the evidence base that PLWH have excess arterial disease to also include PAD. The exact biological mechanisms causing this excess risk remain to be elucidated. Until then, focus on management of modifiable traditional risk factors is important.”

While Dr. Knudsen’s study participants were mostly male and white, the U.S. cohort Women’s Intragency HIV Study (WIHS, pronounced “wise”) also reported on PAD, and the majority of their participants were black (including the HIV-negative but vulnerable to infection control group).

“[PAD] increases cardiovascular disease (CVD) risk by 3-6 fold and is associated with physical function decline and increased mortality,” WIHS reported. “HIV and HCV [hepatitis C virus] infections are not associated with greater PAD risk in WIHS. However, the high PAD prevalence in our cohort is striking; general population studies show a greater than 25% prevalence at ages greater than 20 years older.”

In contrast, nearly 30% of the WIHS participants had PAD, no matter their HIV or HCV status, or age. What did make a difference was longer smoking history, greater waist circumference and pulse pressure, and black race.

“Our findings suggest that smoking cessation and blood pressure control are important early targets in women with and at risk for HIV,” WIHS noted.

The WIHS team also used ABI, and its research in this area continues. The European group also reported more PAD with increasing age.

Late Breaker LB747

Abacavir and heart risk

The large European D:A:D study (Data Collection on Adverse Events of Anti-HIV Drugs) noted that it reported back in 2008 finding an increased risk of heart attack (myocardial infarction, or MI) in people taking abacavir (brand name Ziagen, found in Epzicom and Triumeq). Since then, there’s been more research finding—and not finding—that association.

At this year’s CROI, the D:A:D study team reported that while fewer people with pre-existing risks for heart disease are prescribed abacavir, there was still an association between the drug and heart attack risk.

Abstract 96

Long-acting naltrexone for newly released prisoners

“Why did we focus on prisoners? The United States incarcerates more people than any other country on the planet Earth. In the United States, HIV is roughly three times greater in prevalence in the prison population when compared to the community. In order to achieve the wonderful [UNAIDS] goal of 90% of people living with HIV [PLWH] on antiretrovirals with the end result goal of 90% with viral suppression [after 90% are diagnosed, called “90-90-90”], we really need to pay special attention to our incarcerated population—in particular those with comorbidities of alcohol and opioid substance use disorders. Although we know that PLWH in prison can receive antiretroviral therapy and achieve viral suppression, for the most part prior to release, that benefit is quickly lost soon after release, particularly three months after release, such that the majority have lost all benefit with very few having viral suppression.

“In the United States we also have several effective medications that are FDA approved for the treatment of alcohol and opioid use disorders. One long-acting medicine used for alcohol and opioid use disorder shown to prevent relapse and opioid overdose is extended-release naltrexone. However, very few of our jails and prisons in the United States offer medications before release to prevent relapse.

“Although we know there’s a whole host of factors involved in the interruption of the treatment cascade for this group, relapse to alcohol and other substance use disorder occurs quickly in this group. Particularly those with opioid or alcohol use and in turn, on its own, significant morbidity such as overdose. Overdose is the number one cause of death for recently released prisoners. But in addition, for those living with HIV, interruptions in the HIV treatment cascade can be associated with loss of viral suppression, which in turn as we know is associated with increased morbidity for the individual and, from a public health standpoint, is associated with increased transmission.”

Dr. Sandra Springer, of Yale University, reporting on her team’s findings from two randomized placebo-controlled clinical trials—the highest standard there is in medical research—finding better viral load suppression and freedom from opioid and alcohol use in people living with HIV after their release from prison when given a monthly injection of extended-release naltrexone (brand name Vivitrol) for six months, beginning with a week before their release, and suggesting the evidence-based use of opioid antagonists for released inmates with dependency, for both individual and public health.

Abstract 88

Drop in HIV with PrEP

The title of Abstract 88 says it all: “Rapid Reduction in HIV Diagnoses after Targeted PrEP Implemented in NSW, Australia.”

“Randomized trials of pre-exposure prophylaxis (PrEP) in men who have sex with men (MSM) have reported efficacy of more than 85%,” the Australian team reported in its abstract. “Modelling predicts PrEP will have greatest population-level efficacy if rapidly targeted, with high coverage, to those at high risk. In New South Wales (NSW), more than 80% of HIV diagnoses occur in MSM. Despite substantial increases in testing and treatment since 2012, and the state approaching the UNAIDS 90/90/90 targets [see below], annual HIV diagnoses varied little over the decade to 2016.

“The high level, targeted, and rapid roll-out of PrEP in NSW led to a 35% decline in state-wide HIV diagnoses in MSM, and a 44% decline in early HIV infections in MSM, to levels unprecedented since the beginning of the HIV epidemic. This was achieved less than one year after the target recruitment was reached. In a concentrated epidemic with high testing and treatment coverage, PrEP scale-up led to a rapid decline in HIV transmission at the population level.”

After recruiting and providing PrEP to 3,700 MSM vulnerable to HIV, only one of the men was HIV-positive a year later. There are almost twice that many men now on PrEP through the study and enrollment is continuing. The 35% drop in new diagnoses from one six-month period to another represented a difference of 101 new diagnoses vs. 156 diagnoses previously.

What’s Australian for “good job”?

Abstract 86

Crying out for PrEP

“The sobering findings that black men and women constitute a higher proportion of those with indications [need] for PrEP, that blacks and Hispanic Americans account for a significant majority of those with indications for PrEP, and that PrEP coverage is lowest among black and Hispanic Americans, is a call to urgent action. We must correct this health inequity if we are to end the epidemic for all Americans.”

Dr. Dawn K. Smith of the Centers for Disease Control (CDC), on the agency’s new estimates on the racial disparities between who gets the Truvada for PrEP HIV prevention pill in the U.S. and who needs it most. Men who have sex with men (MSM) remain a high priority for PrEP, but especially black MSM, according to the report. See the abstract and webcast for estimates on heterosexuals and people who inject drugs. (By Race/Ethnicity, Blacks Have Highest Number Needing PrEP in the United States, 2015 [latest figures])