Data on individuals’ absorption of Truvada (tenofovir/emtricitabine) supports so-called on-demand pre-exposure prophylaxis (PrEP), a non-daily regimen geared around the timing of intercourse. Researchers have outlined this position in an opinion piece published in The Lancet HIV.

The IPERGAY trial, the results of which were first presented in 2014, instructed French and Canadian men who have sex with men (MSM) to take two tablets of Truvada two to 24 hours before having intercourse and then one tablet 24 and 48 hours after having intercourse (for a total of four tablets). On the population level, this dosing strategy reduced the risk of contracting HIV by 86 percent. Those who contracted the virus were not taking PrEP at the time.

The participants took a median 15 tablets of Truvada per month, or about four per week. Previous research estimated that taking four tablets per week provides maximum protection against HIV. This means researchers could not say for sure whether the particulars of the dosing instructions were responsible for the high level of protection or whether the overall regularity of pill taking was the real reason.

Looking at the 2015 Cell-PrEP study, the opinion article’s authors believe they have found the key to supporting on-demand PrEP as an effective HIV prevention strategy. The study included 21 HIV-negative partcipants who had never taken Truvada. The participants were instructed to take Truvada daily for 30 days. They had their drug levels measured on their first day taking the regimen, as well as on days 3, 7, 20 and 30.

Using mathematical modeling, the researchers estimated that on day 1, 17 percent of the partcipants had drug levels high enough to confer protection against HIV. On days 2, 3, 4 and 7, the proportion with such a drug level increased to 44 percent, 71 percent, 84 percent and 90 percent, respectively. This meant that four doses reduced the overall risk of contracting HIV by an estimated 98 percent.

As a parallel, the IPERGAY protocol is based on a four-pill regimen centered around potential exposure to the virus. Consequently, the authors of the Lancet HIV editorial believe that the on-demand protocol confers “high protection for MSM and transgender women.” The protection holds, the scientists argue, even when people have sex infrequently and thus take a lower average number of pills per week.

The authors write: “A caveat for [on-demand] dosing is adherence also requires anticipation of sex, and protection may be less forgiving of missed tablets than daily use.”

In Cell-PrEP, 16 percent of the participants did not develop protective levels of Truvada after four doses, and 29 percent did not reach such levels after three doses. Other particulars of how individuals metabolize Truvada may make missing doses of the on-demand protocol riskier than missing doses of a daily Truvada regimen.

However, some people may not want to take Truvada on a daily basis, particularly if they have intercourse relatively infrequently. For these individuals, an on-demand dosing schedule may provide an appealing alternative. Such a regimen, write the editorial authors, “is clearly preferable to no PrEP at all.”

More research is needed to determine on-demand PrEP’s effectiveness for vaginal sex. Truvada is absorbed differently into vaginal tissues compared with rectal tissues. Women tend to need to be more faithful to a daily PrEP regimen to achieve maximum protection than MSM do.

To read the abstract for the Cell-PrEP study, click here. 

To read the editorial’s abstract, click here.