An open pre-exposure prophylaxis study (PrEP) with Truvada in Botswana, with heterosexual people, has shown very high adherence rates. About 90% of participants had functional levels of the drug in the blood; there was a high agreement between self-reported adherence and serum drug levels in study subjects; and there were no HIV infections as reported to the Eighth International Society Conference on HIV and AIDS pathogenesis, treatment and prevention (IAS
2015) last month.
Participants had taken part in the previous, placebo-controlled PrEP study "TDF2" that took place between 2007 and 2011 which demonstrated an efficacy of 62% $ for active PrEP versus placebo.
For the present study, attempts were made to contact all of the 1219 participants of the original TDF2 study. Faith Henderson of the US Centers for Disease Control and Prevention (CDC) commented that, with a three year interval and a highly mobile population such as Botswana, it was difficult to contact all participants. However, 736 participants of TDF2 (60%) were eventually crawled. Of these, 229 (31%) were eligible to receive PrEP using the same criteria as the original TDF2 study - in this very high prevalence country, study subjects had between 19 and 39 years of age (90% in TDF2 had a mean age of twenty years) and were sexually active. The main reasons for the exclusion was that at the time of this new study the person was now seropositive, had blood results indicative of kidney disease or, in relation to women, were pregnant or breastfeeding.
Truvada and condoms were dispensed once a month and participants were tested for HIV and received risk reduction counseling in three months. Participants also received text messages or phone calls as reminders of adherence.
Of the 229 people enrolled, 60 completed 10 years or more of the maximum of twelve monthly study visits and the patient-years of data collected was 76% of the maximum possible. Fifty-six percent of the participants were male, and the women were about 60 most likely not to complete the study - the reasons why they are being investigated in qualitative studies. Just another factor associated with non-conclusion was that people who experienced significant side effects were twice as likely not to complete the study.
The open study was designed primarily to measure any behavioral change and also to measure adherence. On average, each monthly visit, 71% of participants reported only one sexual partner in the previous month, 9% two and 2.4% three or more (not all participants reported number of partners). The average number of sexual partners in the previous month was about one per man during the study but declined from one to 0,75 in women. The average number of self-reported self-reported sex in the previous month decreased from 1,9 to 1.2 in men and from 1,45 to 0,95 in women.
Auto grip reported was high. When asked if they had taken Truvada the last three days before their clinic visit, 88% said they had taken all three times, 5.5% once or twice and 6,7% had not taken PrEP.
In total, 120 participants (52%) had measured drug levels in blood samples for tenofovir. Among these, 100 had tenofovir levels above five nano grams per milliliter (ngml), indicative of some use last week and 94 over 25ngml, indicating clinically useful levels. These levels were concordant with self-reported adherence: in participant samples who said they had taken all three pills in the last three days, drug levels were higher than 25ngml in 92 women and 98 men; if two doses were reported, drug levels were on 25ngml in 90; if once in the last three days, 86,5; and if no doses were reported in the last three days, 42 of the women and 73 of the men had levels more 25ngml.
In a subset of 30 participants, the proportion of people with 25ngml levels were 93%, 93%, 100%, 93% and 90% months 1, 3, 6, 9 and 12 of the study, so there was little or no evidence of any drop in adhesion. Women were 9% less prone to non-adherence than men to have clinically useful blood levels of tenofovir, and people who did not report any unprotected sex also had slightly lower adherence, although this difference was not significant.
No HIV infection occurred in any study participant. Although this was not conceived as an efficacy study, five or six HIV infections would have occurred if the background HIV incidence was at the same rate seen in the placebo arm of the original TDF2 study (3.1 per year).
Drug level analysis and qualitative data will be presented, but - although there should be a strong caveat about the use of text and phone reminders in this study - shows high levels of effective adherence to PrEP can be achieved among a heterosexual African population who they lack it.
The big question now is whether the government of Botswana and other agencies will extend its already impressive level of provision of antiretroviral therapy to people with HIV to cover the provision of PrEP for the proportion of HIV-negative people who remain at significant risk.
Henderson F et al. Characteristics and oral PrEP adherence in the TDF2 open-label extension in Botswana. Eighth IAS Conference on HIV Pathogenesis, Treatment and Prevention (IAS 2015), Vancouver. Abstract TUAC0203, 2015.
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