Two studies presented at the 8th International AIDS Society in Vancouver Canada (July 19 to 23) offer critical insights about PrEP and cisgender heterosexual women. One found very high rates of adherence and no infections among women taking daily PrEP in an open label fashion, while the other measured adherence and acceptance of three dosing strategies, of which a qualitative analysis suggests that common education and adherence programs may actually worsen suspicion about PrEP and lower adherence.
In the first study, an open label continuation of the Centers for Disease Control and Prevention (CDC) funded TDF2 trial, the CDC's Faith Henderson presented an analysis of adherence among 229 heterosexual cisgender men and women who rolled over from the larger TDF2 efficacy trial (where half were randomized to receive Truvada and half did not). Individuals in TDF2 were asked if they would like to receive 48 weeks of Truvada and be followed regularly. Those who agreed, 229 in all, were tested regularly for HIV and had their adherence measured by both self report and blood level testing for the presence of tenofovir.
Forty-five percent of the participants were female and roughly 70% were single. When looking at self-reported adherence, roughly 90% reported having good or excellent adherence and this held up through the course of the study. Blood level testing in 120 of the 229 revealed that self-reported adherence was highly correlated with having detectable tenofovir in blood. While this is encouraging, and women were validated to have very high adherence, female sex was associated with slightly lower adherence levels.
Overall, the number of sex partners decreased by 12% and the number of condomless sex acts decreased by 39% during the course of the study.
There were no HIV transmissions, though statistics from the earlier TDF2 efficacy trial would have predicted 5 or 6, backing up the finding that Truvada can work well in HIV-negative women.
HPTN 067 (ADAPT)
HPTN 067 is not an efficacy study. Rather, it is designed to measure the coverage of sex acts, acceptability and adherence involved in three Truvada dosing strategies: daily, time-driven (two doses per week not driven by sex) and event-driven, where one dose is taking within 24 hours before sex and another dose 2 hours after.
There are three separate branches of ADAPT, two in men who have sex with men (MSM) and transgender women in either Harlem or Bangkok, and one in heterosexual cisgender women in South Africa. This article focuses on the study in South Africa.
As Dr. Robert Grant from the University of California San Francisco (UCSF) reported, 179 women were randomized 1:1:1 to the three dosing strategies. HIV incidence was high, with 6.8% not enrolled due to being HIV+ at enrollment, indicating that the study was being properly deployed in groups of women at particularly high risk for HIV infection. The median age was 26, 80% were never married and 83% were unemployed.
Based on a device that electronically measured doses dispensed and self-report through weekly phone calls, overall adherence was much better with daily dosing than the other two intermittent dosing strategies, with 75% having good coverage if they were assigned to take Truvada daily, compared with 56% assigned to time-driven dosing and 52% with sex-driven dosing.
To determine the barriers and facilitators to drug taking, Rivet Amico from the University of Michigan, worked with researchers and community to conduct focus groups and interviews with 60 of the women in the study.
Amico explained that through two types of psychosocial analyses it was possible to identify perceptions and values that affected adherence. On one end of the spectrum, among women with the least adherence, Amico found high levels of distrust: about the drug, about the research process and about the medical establishment. On the other end of the spectrum, she defined the group of high adherers as having "mutuality," whereby a participant felt there could be a high degree of benefit both to herself and to her community by participating in the research study. In between were those who felt uncertain about the drug and the study, and those who wished to be in alignment with the studys aims, but who nonetheless struggled with adherence.
One conclusion that Amico and her team drew from the qualitative work, was that adherence to clinical care and medication taking could be well supported through traditional means. These could include reminder calls and texts and validated adherence support programs support women in keeping their appointments and taking their medications.
Conversely, and quite important, utilizing these measures, which often assume that a womans wishes about PrEP are in concordance with the researcher or doctor, could push women to report that they are more adherent than they actually are. It is likely, for women who feel more distrust and uncertainty, that other types of interventions will be needed, both for research studies and for programs designed to combine behavioral and biomedical prevention strategies.
David Evans is the director of research advocacy for Project Inform.
R Grant, et al. HPTN 067/ADAPT Methods and Results from Women in Cape Town. IAS 2015, Vancouver, Canada. July 1922, 2015.