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IAS 2015: High Adherence and No HIV Infections Seen in Heterosexual PrEP Study in Botswana

A study of open-label Truvada HIV pre-exposure prophylaxis (PrEP) among heterosexual people in Botswana found very high adherence rates. Around 90% of participants had useful levels of the drug in their blood, there was a high concordance between self-reported adherence and drug levels, and there were no HIV infections, according to a presentation at the 8th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention last month in Vancouver.

[Produced in collaboration with Aidsmap.com]

The participants in this open-label extension had all previously taken part in the TDF2 placebo-controlled study of PrEP, which took place between 2007 and 2011 and found an efficacy of 62% for tenofovir/emtricitabine (Truvada) PrEP versus placebo.

For the present study, researchers attempted to contact all 1219 participants in the original TDF2 study. Presenter Faith Henderson of the U.S. Centers for Disease Control and Prevention commented that, with a 3-year gap and a highly mobile population in Botswana, it was hard to contact all participants. However, 736 TDF2 participants (60%) were eventually traced.

Of these, 229 (31%) were eligible to take PrEP using the same criteria as the original TDF2 study -- which, in this very high-prevalence country, were that they were between 19 and 39 years old (90% in TDF2 were in fact in their twenties) and were sexually active. The main reasons for exclusion were that the person was now HIV-positive, had blood results indicative of kidney disease or, for women, that they were pregnant or breastfeeding.

Truvada and condoms were dispensed once a month and participants were tested for HIV and received risk-reduction counseling once every 3 months. Participants also received text messages or phone calls as adherence reminders.

Of the 229 people enrolled, 60% completed 10 or more of the maximum of 12 monthly study visits, and the number of patient-years of data collected was 76% of the possible maximum. 56% of participants were male, and women were about 60% more likely not to complete the study -- the reasons why are being investigated in qualitative studies. The only other factor associated with non-completion was that people who experienced significant side effects were twice as likely not to complete the study.

The open-label study was primarily designed to measure any behavioral change and also to measure adherence. Averaged over each monthly visit, 71% of participants reported only 1 sexual partner in the previous month, 9% had 2 partners, and 2.4% had 3 or more (not all participants reported number of partners). The average number of sexual partners in the previous month stayed at about 1 for men during the study, but declined from 1 to about 0.75 for women. The average number of self-reported condomless sex acts in the previous month declined from 1.9 to 1.2 for men and from 1.45 to 0.95 for women.

Self-reported adherence was high. When asked if they had taken Truvada in the last 3 days before their clinic visit, 88% said they had taken it all 3 times, 5.5% said once or twice, and 6.7% said they had taken none.

Altogether, 120 completing participants (52%) had tenofovir drug levels measured in blood samples. Among these, 100% had tenofovir levels over 5 nanograms per milliliter (ng/mL), indicative of some use in the last week, and 94% had over 25 ng/mL, indicating clinically useful levels. These levels were concordant with self-reported adherence. In samples from participants who said they had taken all 3 pills in the last 3 days, drug levels were over 25 ng/mL in 92% of women and 98% of men; if 2 doses were reported, drug levels were over 25 ng/mL in 90%; if 1 dose was reported, levels were useful in 87%; and if no doses were reported, just 42% of women and 73% of men had levels over 25 ng/mL.

In a subset of 30 participants, the proportion of people with tenofovir levels over 25 ng/mL were 93%, 93%, 100%, 93%, and 90% at months 1, 3, 6, 9, and 12 of the study, so there was no or little evidence of any fall-off in adherence. Women were 9% less likely than men to have clinically useful tenofovir blood levels, and people who did not report any condomless sex also had slightly lower adherence, though this difference was not significant.

No HIV infections occurred in any of the study participants. Although this was not designed as an efficacy study, 5 or 6 new infections would have occurred if background HIV incidence was at the rate seen in the placebo arm of the original TDF2 study (3.1% per year).

Further drug level analysis and qualitative data will be presented, but -- although there must be a big caveat about the use of text and phone reminders in this study -- it does show that high and effective levels of adherence to PrEP can be reached among an African heterosexual population who are in need of it.

The big question now is whether the Botswana government and other agencies will extend their already impressive level of antiretroviral therapy provision to people with HIV to cover PrEP provision for HIV-negative people who remain at significant risk.

8/12/15

Reference

F Henderson, A Taylor, L Chirwa, et al. Characteristics and oral PrEP adherence in the TDF2 open-label extension in Botswana. 8th International AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention. Vancouver, July 19-22, 2015. Abstract TUAC0203.