Sexual Relationships and PrEP Adherence and Adherence Gaps

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Sexual Relationships and PrEP Adherence and Adherence Gaps

Abstract and Introduction


Objective To assess the role of sexual relationships on levels and patterns of adherence to medication for pre-exposure prophylaxis against HIV.

Methods We enrolled 1147 HIV-negative individuals in long-term serodiscordant relationships at 3 sites in Uganda from the Partners Pre-exposure Prophylaxis Study, a randomized placebo-controlled trial of daily oral tenofovir and emtricitabine/tenofovir. We used generalized estimation equations to assess the effects of sexual relationships on low adherence (<80%) and on gaps in adherence.

Results Fifty-three percent were male, 51% were 18–34 years and 24% were polygamous. Participants who reported sex in the past month with someone other than their primary partner and with <100% condom use were more than twice as likely to have low adherence [adjusted odds ratio (aOR) = 2.48, 95% CI: 1.70 to 3.62] compared with those who had sex with only their primary partners and 100% condom use. Using the same reference group, those who abstained from sex in the previous month had 30% increased odds of low adherence (aOR = 1.30, 95% CI: 1.05 to 1.62) and participants in nonpolygamous marriages who reported sex with both their primary and other partners and <100% condom use were almost twice as likely to be low adherers (aOR = 1.76, 95% CI: 1.01 to 3.08). At least one 72-hour gap in adherence was seen in 598 participants (54.7%); 23.2% had at least one 1-week gap.

Conclusions Risk of low overall adherence was higher in participants who reported sex outside primary partnerships and suboptimal condom use, as well as in those who abstained from sex. Adherence gaps were common, potentially creating risk for HIV acquisition.


HIV antiretroviral medications have been shown to reduce the transmission of the virus when used for prophylaxis by HIV-negative individuals. Based on these studies, the US Food and Drug Administration approved the use of tenofovir (TDF)/emtricitabine; an antiretroviral drug for pre-exposure prophylaxis (PrEP) by HIV-negative individuals with a high risk of acquiring sexually transmitted HIV. PrEP is now one of the few available HIV prevention strategies in a field where vaccines and a cure have long been elusive.

Adherence to prescribed antiretroviral medication is known to be vital to successful viral suppression and better clinical outcomes in HIV treatment settings. Additionally, adherence has been identified to be a key component of effective PrEP. Poor adherence to assigned medication is likely the primary reason for the null findings in the FEM-PREP and VOICE studies, which assessed the efficacy of oral and topical TDF for HIV PrEP among heterosexual African women.

Because PrEP is a new tool in HIV prevention, there are limited data on the associations of adherence to this medication. However, we recently reported that several factors including age, heavy alcohol use, being in a polygamous marriage, and sexual behavior might affect adherence to HIV PrEP. For the purposes of this study, polygamy status was defined at baseline and referred to 1 of 2 situations: (1) an HIV-negative man with more than 1 wife, one of whom was HIV-positive or (2) an HIV-negative woman whose HIV-infected husband had more than 1 wife. Marriage was be defined by law, religious, or local custom. We assessed quarterly sexual behavior through interviewer-administered questionnaires, and quarterly adherence was assessed using the medication event monitoring system (MEMS; Aardex, Union City, CA). We found that HIV-negative participants who reported sex with only people other than their primary sexual partners were twice as likely to have low rates of adherence as compared with those who only reported sex with their primary partners (aOR = 2.3, 95% CI: 1.3 to 3.8). In a second study using short message surveys for assessing sexual behavior, participants who did not have sex on a particular day were almost twice as likely to miss a dose of PrEP medication on that same day (aOR = 1.87, 95% CI: 1.35 to 2.60).

To better understand the relationship between sexual behavior and adherence to PrEP, in this study, we assessed the associations of sexual behavior with monthly adherence rates, which may better assess short-term effects of sexual behavior and with patterns of adherence to PrEP. Patterns may be more informative than summary measures of adherence (eg, median values) because lengthy gaps may expose an individual to more risk for HIV acquisition compared with occasional missed doses. We also explore the effect of condom use on adherence within all strata of sexual behavior. We further evaluated the influence of polygamy within strata of sexual behavior to explore more closely the role of polygamy on adherence to PrEP.

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