To benefit from maximum protection against HIV acquisition through vaginal sex, women likely have to adhere better to the daily regimen of Truvada (tenofovir disoproxil fumarate/emtricitabine) as pre-exposure prophylaxis (PrEP) compared with men who have sex with men (MSM), aidsmap reports. This apparent fact is driven by differences in the way that the drugs in Truvada are metabolized in the vagina compared with the rectum.
Additionally, so-called on-demand PrEP, a dosing protocol in which Truvada is taken only in the days surrounding intercourse, has proved highly effective among MSM. However the differences between vaginal and rectal metabolization of Truvada suggest that such a protocol will likely not be very effective among women. Furthermore, women participating in studies of such dosing protocols have adhered poorly to the non-daily-dosing regimens, diminishing their protection against HIV.
Such analyses were presented at the 9th International AIDS Society Conference on HIV Science in Paris (IAS 2017).
The first presentation was from Robert M. Grant, MD, MPH, a professor at the University of California, San Francisco, who was the head of the iPrEx trial that first proved PrEP’s effectiveness among MSM and transgender women in 2010. He noted that in clinical trials of PrEP, no MSM or trans woman for whom tests indicated they were taking four to seven tablets of Truvada weekly contracted HIV. But among cisgender women in PrEP trials, 24 individuals have tested positive for HIV when drug levels measured before, after or both before and after the HIV-positive test result indicated that they were taking four or five tablets of Truvada per week. No cisgender women participating in PrEP trials have contracted HIV while tests indicated they were taking six or seven tablets of Truvada weekly.
Two studies, the Kenya/Uganda iPrEP study and the ADAPT study, included women who were instructed to follow a non-daily-dosing PrEP regimen geared around the timing of sex. They found that women adhered poorly to such a regimen. In each study, just about half the women instructed to follow such a protocol did so correctly.
A second presentation from Angela Kashuba, PharmD, a professor at the University of North Carolina Eshelman School of Pharmacy, looked more closely at how the two drugs included in Truvada are metabolized in the rectum and vagina, respectively. Previous research has shown that after a single dose of Truvada, drug levels of the tenofovir and emtricitabine components are a respective 100 and 50 times lower in the vaginal tissue compared with the rectal tissue.
In primate research, by the eighth day of daily dosing of Truvada, tenofovir levels in the vagina are actually much higher than in the rectum; meanwhile, it takes just one or two days of daily use for tenofovir to hit peak levels in the rectum. But as for emtricitabine, daily use never leads to levels in vaginal tissues as high as in rectal tissues; after eight days of use, vaginal levels are one seventh those seen in the rectum.
Following the last dose of PrEP, tenofovir remains at optimal levels in the cells in rectal tissues for at least five days; even 10 days after the last dose, such intracellular levels of the drug remain at 90 percent of an optimal level. The level of tenofovir in cells in vaginal cells starts falling rapidly after the last dose and reaches 85 percent of an optimal level after just three days. Emtricitabine levels decline in vaginal cells even more rapidly, dissipating within hours.
To read the aidsmap article, click here.
To read the Grant conference abstract, click here.
To read the Kashuba conference abstract, click here.
To watch a webcast of the conference session, click here.