An analysis of blood levels of Truvada (tenofovir disproil fumarate+emtricitabine) among participants in the global iPrEx (Iniciativa Profilaxis Pre-Exposición) study found that U.S. study participants were significantly more likely to take pre-exposure prophylaxis (PrEP) regularly than were their global counterparts. Other indicators of higher adherence to the regimen were older age and riskier sexual practices.
iPrEx was a placebo-controlled phase III trial to determine whether Truvada was effective in preventing HIV infection in men who have sex with men (MSM) and in transgender women. It enrolled 2499 participants in Latin America, Thailand, South Africa and the U.S. between 2007 and 2011. The trial started in the Andes (Peru and Ecuador), so a larger proportion of the overall study population came from that region. Participants in the U.S. comprised 9% of the 1251 people in the iPrEx active arm (i.e., those receiving Truvada rather than the placebo), while Andean MSM and transgender women accounted for 68% of iPrEx active arm participants.
As described in "Patterns and Correlates of PrEP Drug Detection," by Albert Liu, M.D., M.P.H., et al., researchers conducted a cross-sectional analysis that measured Truvada levels at week 8 in the blood of 470 participants randomly selected from the active arm of the iPrEx trial. It also evaluated a cohort of 303 iPrEx participants over 72 weeks to determine consistency of medication adherence. Seventeen percent of people in the week 8 cohort were at U.S. sites, while 44% were in the Andes. The respective numbers for the 72-week longitudinal cohort were 11% from the U.S. and 56% from the Andes.
Slightly over half (55%; 95% confidence interval, range 49%-60%) of all participants studied at week 8 had a detectable level of Truvada in their blood, indicating that they had at least taken the study drug sometimes. That percentage, however, varied quite widely among different cities, from 35% in Lima, Peru, to 90% in San Francisco. Boston came in at 72%, the same rate as Chiang Mai, Thailand.
In the longitudinal analysis, adherence to the study drug was divided into thirds: 31% never had any detectable Truvada levels in their blood, 30% always had such levels, and 39% sometimes had the drug in their blood. Here the highest level of adherence was again in San Francisco, with 67% of participants always having detectable Truvada levels, while Lima had the lowest rate, with only 17% of participants always having detectable levels. Study authors theorized that "research literacy may explain greater drug detection among populations with greater research experience," such as older MSM in the U.S.
Similarly high adherence rates have also been observed in a current PrEP demonstration project among MSM and transgender women in San Francisco, Washington, D.C., and Miami. One month after the project's start, Truvada levels indicating four or more pills were taken each week were observed in 92%, 90% and 73% of participants in these cities, respectively. Data released at the AIDS 2014 conference from the iPrEx Open-Label Extension (OLE) found that those who took at least four pills a week had complete protection from infection.
Globally, older study participants were more likely to have adhered to the medication regimen. Those over age 30 were 5.13 times more likely than those under age 20 to have Truvada in their blood sometimes rather than never (P value = 0.001). Levels of the drug were also detected more frequently in those who engage in higher-risk sexual behaviors, such as receptive anal intercourse without a condom (odds ratio [OR] for detectable level sometimes versus never: 4.29, P value <0.001).
However, overall adherence declined over time, from a 59% probability of detectable Truvada levels prior to week 12 to 44% after week 72. Among the 163 patients who had detectable Truvada levels on their first study visit, 32% stopped taking the drug after a median of 24 weeks. A majority (68%) of the 139 patients who did not have the study drug in their blood on the first visit did not have any detectable Truvada levels at subsequent visits, either.
The iPrEx OLE encouraged the former iPrEx study participants to start or stop PrEP as they wished: 72% chose to start PrEP at enrollment, 6% started PrEP partway through the study, and the rest never took Truvada for HIV prevention. Among those who declined PrEP, the most common reason (50%) was concern about potential side effects. Robert Grant, one of that study's authors, said "This caught [the study team] by surprise because we spent almost all of our time communicating about efficacy and we missed how important safety is to everybody when considering whether to take a medication."
The follow-up study also corroborated the finding that participants who engaged in riskier sexual practices were more likely to use PrEP. For example, 32% of the cohort in OLE reported non-condom receptive anal intercourse. PrEP uptake among that group was 81%, compared to 75% for those who said they did not engage in that practice (uptake P value: 0.003).
Liu and colleagues concluded: "Greater drug detection among those reporting highest risk sexual practices is expected to increase the impact and cost-effectiveness of PrEP."
Barbara Jungwirth is a freelance writer and translator based in New York.
Follow Barbara on Twitter: @reliabletran.
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