Nondaily Treatment an Option for Those at High Risk for HIV

Pam Harrison

July 23, 2015

VANCOUVER, British Colombia — Although pre-exposure prophylaxis is more protective against HIV infection when it is administered daily, for some people, nondaily administration is feasible and acceptable, results from the phase 2 ADAPT study suggest.

"We know that any biomedical technology will disseminate and be used effectively only if it can be adapted to peoples' lives," principal investigator Robert Grant, MD, from the University of California at San Francisco, told reporters attending a news conference here at the 8th International AIDS Society Conference.

"We identified many perceived advantages and disadvantages of pre-exposure prophylaxis dosing regimens that will help us develop good clinical practices to maximize the appropriate dissemination and its integration with treatment initiatives," he explained.

The open-label ADAPT trial involved two cohorts of men who have sex with men and transgender women — 178 participants from Bangkok and 179 from New York City — and a cohort of 179 black single women at high risk for HIV from Cape Town, South Africa.

All participants were HIV-negative at baseline and were randomized to one of three pre-exposure prophylaxis regimens — daily, time-driven, or event-driven — for 24 weeks.

The daily regimen involved a fixed-dose combination of emtricitabine and tenofovir (Truvada, Gilead Sciences) taken once a day; the time-driven regimen involved the combination pill taken twice a week and one pill taken up to 24 hours after sex; and the event-driven regimen involved the combination pill taken 4 days to 96 hours before sex and another taken up to 24 hours after sex.

ADAPT Trial

The investigators evaluated self-reported adherence and analyzed blood for detectable levels of tenofovir.

This study "demonstrated that single young black African women at high risk for HIV infection in South Africa can take and adhere to pre-exposure prophylaxis, and most women prefer daily dosing," Dr Grant reported.

Daily dosing was also attractive to participants in Bangkok and New York City.

In the New York cohort, 66% of participants in the daily group had complete coverage during sex, as did 47% of those in the time-driven group and 52% of those in the event-driven group, reported Sharon Mannheimer, MD, from the Columbia University Mailman School of Public Health in New York City.

Adherence was significantly better with the daily regimen than with either the time-driven or event-driven regimens, as indicated by higher tenofovir blood levels at week 10 (48% vs 35% vs 19%).

"For nondaily pre-exposure prophylaxis, incomplete coverage of sex acts was mostly related to lack of postsex dosing," Dr Mannheimer said. "Additional interventions may be needed to optimize adherence."

Adherence and drug levels were much better in the Bangkok cohort than in the New York cohort.

In the Bangkok cohort, 85% of participants in the daily group achieved complete coverage before and after sex, as did 84% of those in the time-driven group and 74% of those in the event-driven group, reported Timothy Holtz, MD, MPH, from Emory University in Atlanta.

As in the New York cohort, adherence rates were significantly higher in the daily group than in the time-driven or the event-driven groups (global P < .001), as indicated by tenofovir blood levels at week 10 (100% vs 97% vs 93%).

Dosing Options

The advantages of a daily regimen include the fact that a single pill can be easily taken along with daily vitamins and patients are able to set a time when they take their pill regardless of sex, Dr Holtz pointed out. There is also no need to carry the pills around in case sex happens unexpectedly, and no need to disclose the use of pre-exposure prophylaxis to anyone.

Disadvantages include concerns about long-term adverse effects and fears of being construed as having HIV.

The advantage of a time-driven regimen is that patients require fewer doses, so there is less concern about adverse effects. In addition, patients do not need to plan their pill-taking around sex, although they do need to keep a few pills on hand in case they have unexpected sex, after which they need to take a pill.

 
I think our confidence in daily dosing is the highest, and we will be recommending daily dosing for most people at this time.
 

The main problems with a time-driven regimen are that patients find it difficult to link the 2-day-a-week pill-taking regimen with routine activities and that it is difficult to hide the fact that a pill has to be taken after sex.

The event-driven regimen requires even fewer doses of the emtricitabine and tenofovir combination, Dr Holtz pointed out. However, patients need to plan for sex, they need to carry pills at all times, and it is difficult to hide the fact that they need to take a pill after sex.

"At this point, it is unclear what the next step will be for nondaily dosing," Dr Grant said.

However, a nondaily pre-exposure prophylaxis regimen is likely to appeal to men and women who have sex less frequently, the investigators report.

"As a medical provider, my obligation is to recommend things that I know work and that I know can fit into peoples' lives and will work for them," Dr Grant explained.

"I think our confidence in daily dosing is the highest, and we will be recommending daily dosing for most people at this time," he said. "But we also need to provide people with good guidance about how to start and stop pre-exposure prophylaxis, because it's only for when people need it," he added. "It's is not for life."

HIV Negative, But at High Risk

Pre-exposure prophylaxis is an important additional intervention for people at high risk for HIV infection, said Gottfried Hirnschall, MD, from the World Health Organization.

Prophylaxis and its potential benefits for HIV-negative people will be addressed in the 2015 WHO guidelines. It will also be recommended that all people infected with HIV receive antiretroviral therapy, regardless of age.

"As we look at the 2014 data, we are glad to see fewer people dying, but there are still 1.2 million people dying each year, and that is 1.2 million people too many. In addition, we're still seeing 2 million people getting newly infected each year, and that is 2 million people too many as well," Dr Hirnschall said. "We need to take full advantage of the prevention benefits from antiretroviral therapy, as shown in a number of trials, if we are going to get to the goal of 90-90-90 by the year 2020."

UNAIDS has set an ambitious goal of having 90% of all people living with HIV know their HIV status by 2020.

The organization also wants 90% of people diagnosed with HIV infection to be on sustained antiretroviral therapy and 90% of those who are receiving therapy to be successfully suppressed.

The HIV Prevention Trials Network is sponsored by the National Institute of Allergy and Infectious Disease, the National Institute of Mental Health, and the National Institute on Drug Abuse. Dr Grant, Dr Holtz, Dr Mannheimer, and Dr Hirnschall have disclosed no relevant financial relationships.

8th International AIDS Society (IAS) Conference. Abstracts MOACO305LB and MOACO306LB. Presented July 20, 2015.

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