Two hundred forty-nine participants reported intentional interruptions in PrEP use at a total of 328 visits that were subsequent to PrEP dispensing (7.1% of all follow-up visits), 65% were from men. Of the 249 participants reporting a PrEP interruption, 192 reported an interruption only once during their visits. Only 1 person reported 7 interruptions throughout their visits. The median length of PrEP interruption was 28 days (interquartile range [IQR]: 7–45). Of the 328 PrEP interruptions reported, 235 visits had a PrEP interruption longer than 7 days (Table 2). The most common reasons reported for an interruption in PrEP use included: breaking up with the study partner living with HIV (27.0%), experiencing side effects or being fearful of side effects (24.4%), not being at home or having a partner who was not at home (17.0%), running out of pills (7.3%), and getting tired of taking pills (7.0%).
PrEP interruptions were reported during 23.8% of visits when any IPV was also reported and 6.9% of visits when IPV was not reported (OR 3.8, 95% confidence interval [CI] = 1.8 to 8.0, Table 3). After adjusting for age and frequency of sex, the association between PrEP interruption and IPV remained significant (adjusted OR = 2.6, 95% CI = 1.2 to 6.0). Additional correlates of self-reported PrEP interruption were considered and included being married to the study partner (OR = 2.4, 95% CI = 1.5 to 3.9), intestinal symptoms (OR = 2.3, 95% CI = 1.8 to 3.2), and having probable depression (OR = 2.1, 95% CI = 1.5 to 3.2) were significantly associated in univariate analysis, but these were no longer significant in the multivariable model.
Interruptions in PrEP use are important to understand, especially for women for whom missed PrEP doses may be less forgiving than men.24 Resumption of PrEP after interruption may coincide with resumption of sexual risk. This scenario is relevant because oral PrEP resumption may provide partial protection until tenofovir is activated and achieves a steady state.25 An analysis within a blinded, placebo-controlled oral PrEP clinical trial of heterosexual serodiscordant couples, found that women reporting IPV in the past 3 months had an increased risk of low adherence by pill count (adjusted risk ratio = 1.5, 95% CI = 1.2 to 1.9) and plasma tenofovir levels (adjusted risk ratio = 1.5, 95% CI = 1.1 to 2.2).16 The current open-label study provides data in a context where PrEP use was encouraged to be aligned with HIV risk, thus adherence may have varied over time more than in placebo-controlled clinical trials. In our study, participants were also encouraged to disclose gaps in PrEP adherence without judgment from study staff or consequence to their research participation so that counseling messages could be tailored to reflect true risk. Although there is still likely to be underreporting of IPV and PrEP interruptions in our data, the strength of the correlation that we observed suggests that violence can undermine the use of PrEP and leave people vulnerable to HIV acquisition.
Although women more frequently reported experiencing physical IPV in our study, men also reported experiencing IPV, particularly verbal violence. Data documenting IPV among men are uncommon, but it is important to document violence experienced by men, as well as women, and consider the adoption of sex-based interventions. Reports of physical violence were more frequent in women than in men, consistent with the findings of other studies in the region where women were mainly the victims of physical abuse.26
There are several strengths and limitations of this study. Key strengths include the use of longitudinal data from a prospective cohort study with >90% retention through follow-up visits and collection of data related to men as victims of IPV. A limitation is the reliance on self-report of IPV events, an inherent limitation of all studies of this nature. Underreporting of IPV could have occurred because there are certain societal expectations and stigma associated with IPV.27 In addition, our questions may not have been sufficiently comprehensive to elicit all reports of IPV. We asked about 3 types of abuse, provided examples, and counselors were trained in nonjudgmental counseling techniques about collecting social harm information. However, the examples did not describe every possible experience of abuse and participants might not have been able to recognize their experience among the listed categories. In addition, IPV is a difficult subject to disclose, especially to study staff, than to close family members and friends.28,29 In our study, IPV was reported less frequently than the 2014 Kenya Demographic and Health Survey where 39% of women and 9% of men reported IPV and the 2010 Uganda Demographic and Health Survey where 60% of women and 40% of men reported IPV.5,6 Another limitation is the use of self-reported PrEP interruption as our measure of PrEP adherence. The study used a medication event monitoring system to capture daily adherence data, but we limited this analysis to the self-reported time off PrEP because we wanted to focus on deliberate interruptions that participants recognized as substantial enough to report. Adherence counseling for PrEP in this open-label study focused on PrEP use being aligned with HIV risk, and thus, participants were encouraged to feel comfortable describing periods when they did not take their pills.
Nonetheless, participants may not have wanted to disclose PrEP interruptions because of social desirability or difficulties with recall and we are unable to assess whether the degree of accuracy in PrEP recall differed among people experiencing and not experiencing IPV. Future studies should use innovative strategies, including qualitative techniques and motivational interviewing to encourage more disclosure.
The results of this study highlight the potential for IPV to impact oral PrEP use and therefore its effectiveness. Adherence support for persistent PrEP use has been recognized as being an important facet of a comprehensive HIV prevention program.30,31 Within PrEP delivery programs, there may be opportunities to identify people experiencing IPV and dovetail IPV interventions with biomedical HIV prevention services for people who are using PrEP, as had been performed in other HIV prevention intervention studies. The SHARE intervention in Uganda, a combination of IPV prevention and HIV prevention services significantly reduced reports of women's physical and sexual IPV and was associated with a lower HIV incidence.32 The IMAGE study in South Africa, combined microfinancing with participatory training on subjects such as domestic abuse. The authors found that the risk of partner violence levels in the past year was reduced by more than half through women's economic and social empowerment.33 Programs like this may lend themselves to being settings to deliver PrEP or market PrEP for women.
The authors thank the couples who participated in this study for their motivation and dedication and the referral partners, community advisory groups, institutions, and communities that supported this work.
Coordinating Center (University of Washington) and collaborating investigators (Harvard Medical School, Johns Hopkins University, and Massachusetts General Hospital): J.B. (protocol chair), C.C. (protocol co-chair), R.H. (project director), Deborah Donnell (statistician), Ruanne Barnabas, J.H., Harald Haugen, Craig Hendrix, Lara Kidoguchi, Mark Marzinke, Susan Morrison, Jennifer Morton, Norma Ware, and Monique Wyatt.
Partners Demonstration Project Team Project sites
Kabwohe, Uganda (Kabwohe Clinical Research Centre): S.A., Edna Tindimwebwa; Kampala, Uganda (Makerere University): Elly Katabira, Nulu Bulya; Kisumu, Kenya (Kenya Medical Research Institute): Elizabeth Bukusi, J.O.; Thika, Kenya (Kenya Medical Research Institute, University of Washington): Nelly Rwamba Mugo, K.N.
Data Management was provided by DF/Net Research, Inc. (Seattle, WA). PrEP medication was donated by Gilead Sciences.
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