Despite Success, "On Demand" HIV Prevention Pill Raises Questions

No Simple Answers Even As Study Shows 86% Risk Reduction in Gay Men

PrEPwomen.jpg is used under a Creative Commons license at https://www.flickr.com/photos/thomasthomas/268846488/
Photograph © ThomasThomas

A study presented on February 24, 2015 at the Conference on Retroviruses and Opportunistic Infections (CROI) in Seattle has shown that HIV pre-exposure prophylaxis (also known as PrEP) can dramatically reduce the risk of acquiring HIV in men who have sex with men (MSM) when taken before, during, and after sex.

The researchers from the French national HIV research agency ANRS, delivered the results of their much-publicized IPERGAY trial, which was halted in October 2014 after the strategy was shown to be extremely effective.

As a result, participants in the placebo group were immediately placed on PrEP.

In quantifying the trial results, the ANRS researchers concluded that PrEP taken "on demand" may reduce the risk of acquiring HIV by as much as 86%.

If further research supports these conclusions, this new strategy could have an enormous impact on transmission rates in high-risk MSM populations, which continue to have the highest incidence of new HIV infections in the U.S. every year.

It also addresses some of the barriers to uptake of PrEP, which is currently prescribed as a once-daily dose of Truvada (tenofovir + emtricitabine). Among the impediments was the demand for daily adherence for non-infected individuals—a reasonable concern given that only a portion of HIV-infected Americans on therapy are able to maintain adequate levels of adherence.

Study Background and Design

The IPERGAY (Intervention Préventive de l'Exposition aux Risques avec et pour les hommes Gays) trial was a randomized controlled study that recruited 400 MSM in France and Montreal.

The trial, which began in February 2012, was envisioned to be the first stage of an ongoing study that would eventually expand to a total of 1,900 participants.

Among the criteria for inclusion, participants had to

  • not have HIV-1 or HIV-2;
  • have an elevated risk of infection (defined as having had condom-less anal sex with at least two different partners in the past six months), and;

The participants would then be placed in either the Truvada arm or the placebo arm. The Truvada and Truvada placebo dosages were prescribed as follows:

  • Two tablets taken within 24 hours before sex (24 hours at the earliest and no later than two hours before);
  • After which, one tablet would be taken every 24 hours during the period of sexual activity (including after the last sexual relation);
  • And finally, one tablet would be taken approximately 24 hours after the previous tablet.

Participants recruited for the study reported having sex an average of ten times a month and having eight different sexual partners ever two months.

The study design also acknowledged the potential for "chem sex" (i.e., sex on illicit drugs that can sometimes continue throughout the course of an entirely weekend), with nearly half indicating psychoactive drug use (e.g., crystal meth, cocaine, etc) within the last 12 months.

Within this context, the study population would be considered to be at the highest risk for HIV acquisition, making the findings all the more significant.

So What Does All of This Mean?

Firstly, a reduction of 86% does not suggest that condoms be abandoned or that PrEP be prescribed in this fashion.

In their presentation, the ANRS researchers reported that the study participants had taken an average of four Truvada doses per week. This suggests that drug concentration in participants’ blood might have been sustained to such levels as to provide "blanket" protection. This conclusion was supported by another CROI presentation from the UK Medical Research Council, which concluded that daily oral Truvada reduced HIV risk in MSM by exactly the same amount: 86%.

Whether the PrEP "on demand" strategy would work in MSM who had sex less frequently (or infrequently) is still debatable, given that fluctuating serum drug levels may correlate to overall higher risk. While it doesn’t in any way undermine the validity of the IPERGAY results, it does suggest that caution be taken when drawing conclusions.

At the same time, the study does not suggest that PrEP "on demand" would work the same for all high-risk groups. Recent research from the University of North Carolina has suggested that PrEP may require far greater adherence in woman than in MSM—in fact, almost perfect adherence.

According to the research, Truvada concentrations in vaginal tissue aren’t anywhere near as high as in rectal tissue. As a result, MSM may be able to achieve protective goals with as little as 2-3 doses per week, while women would not likely not be able to miss a single dose ever.

Until further research can expand upon these findings, the Centers for Disease Control and Prevention (CDC) recommend the continuation of current guidelines regarding PrEP usage.

We are pleased to have been named one the "Best HIV/STD Health Blogs" of 2015 by the editors of San Francisco-based Healthline.

Sources:

Molina, J; Fonsart, C.; Spire, B; et al. "On Demand PrEP With Oral TDF-FTC in MSM: Results of the ANRS Ipergay Trial." 2015 Conference on Retroviruses and Opportunistic Infections (CROI); July 24, 2015; Seattle, Washington; abstract 23LB.

McCormack, S.; Phillips, A.; Johnson, A.; Gill, N.; and Gazzard, B. "Pragmatic Open-Label Randomised Trial of Preexposure Prophylaxis: The PROUD Study." 2015 Conference on Retroviruses and Opportunistic Infections (CROI); July 24, 2015; Seattle, Washington; abstract 22LB.

Cottrell, M.; Yang, K.; Prince, H.; et al. "Predicting effective Truvada PrEP dosing strategies with a novel PK–PD model incorporating tissue active metabolites and endogenous nucleotides (EN)." HIV Research for Prevention Conference. 28-31 October, 2014; Cape Town, South Africa; oral abstract 22.06 LB.

Continue Reading