Accuracy of Self-Report and Pill-Count Measures of Adherence in the FEM-PrEP Clinical Trial: Implications for Future HIV-Prevention Trials

Oral emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) has been evaluated as pre-exposure prophylaxis (PrEP). We describe the accuracy of self-reported adherence to FTC/TDF and pill counts when compared to drug concentrations in the FEM-PrEP trial. Using drug concentrations of plasma tenofovir (TFV) and intracellular tenofovir diphosphate (TFVdp) among a random sub-sample of 150 participants assigned to FTC/TDF, we estimated the positive predictive value (PPV) of four adherence measures. We also assessed factors associated with misreporting of adherence using multiple drug-concentration thresholds and explored pill use and misreporting using semi-structured interviews (SSIs). Reporting use of ≥1 pill in the previous 7days had the highest PPV, while pill-count data consistent with missing ≤1day had the lowest PPV. However, all four measures demonstrated poor PPV. Reported use of oral contraceptives (OR 2.26; p=0.014) and weeks of time in the study (OR 1.02; p<0.001) were significantly associated with misreporting adherence. Although most SSI participants said they did not misreport adherence, participant-dependent adherence measures were clearly unreliable in the FEM-PrEP trial. Pharmacokinetic monitoring remains the measure of choice until more reliable participant-dependent measures are developed

Injection practices and sexual behaviors among persons with diagnosed HIV infection who inject drugs - United States, 2015-2017.

During 2016, 6% of persons in the United States who received a diagnosis of human immunodeficiency virus (HIV) infection had their HIV infection attributed to injection drug use (1). Injection practices and sexual behaviors among HIV-positive persons who inject drugs, such as injection equipment sharing and condomless sex, can increase HIV transmission risk; nationally representative estimates of the prevalences of these behaviors are lacking. The Medical Monitoring Project (MMP) is an annual, cross-sectional survey that reports nationally representative estimates of clinical and behavioral characteristics among U.S. adults with diagnosed HIV (2). CDC used MMP data to assess high-risk injection practices and sexual behaviors among HIV-positive persons who injected drugs during the preceding 12 months and compared their HIV transmission risk behaviors with those of HIV-positive persons who did not inject drugs. During 2015-2017, approximately 10% (weighted percentage estimate) of HIV-positive persons who injected drugs engaged in distributive injection equipment sharing (giving used equipment to another person for use); nonsterile syringe acquisition and unsafe disposal methods were common. Overall, among HIV-positive persons who injected drugs, 80% received no treatment, and 57% self-reported needing drug or alcohol treatment. Compared with HIV-positive persons who did not inject drugs, those who injected drugs were more likely to have a detectable viral load (48% versus 35%; p = 0.008) and engage in high-risk sexual behaviors (p<0.001). Focusing on interventions that reduce high-risk injection practices and sexual behaviors and increase rates of viral suppression might decrease HIV transmission risk among HIV-positive persons who inject drugs. Successful substance use treatment could also lower risk for transmission and overdose through reduced injection

The sexual risk context among the FEM-PrEP study population in Bondo, Kenya and Pretoria, South Africa.

Incidence rates in the FEM-PrEP and VOICE trials demonstrate that women from diverse sub-Saharan African communities continue to be at substantial HIV risk.To describe and compare the sexual risk context of the study population from two FEM-PrEP trial sites-Bondo, Kenya, and Pretoria, South Africa.At baseline we collected information about demographics, sexual behaviors, and partnership beliefs through quantitative questionnaires with all participants (Bondo, n = 720; Pretoria, n = 750). To explore the sexual risk context, we also conducted qualitative, semi-structured interviews with HIV-negative participants randomly selected at several time points (Bondo, n = 111; Pretoria, n = 69).Demographics, sexual behavior, and partnership beliefs varied significantly between the sites. Bondo participants were generally older, had fewer years of schooling, and were more likely to be employed and married compared to Pretoria participants. Bondo participants were more likely to report multiple partners and not knowing whether their partner had HIV than Pretoria participants. A significantly higher percentage of Bondo participants reported engaging in sex without a condom with their primary and other partners compared to Pretoria participants. We found a borderline association between participants who reported not using condoms in the 4 weeks prior to baseline and lower risk of HIV infection, and no association between having more than one sexual partner at baseline and HIV infection.Despite significantly different demographics, sexual behaviors, and partnership beliefs, many women in the FEM-PrEP trial were at risk of acquiring HIV as demonstrated by the sites' high HIV incidence. Though gender dynamics differed between the populations, they appear to play a critical role in women's sexual practices. The findings highlight different ways women from diverse contexts may be at-risk for HIV and the importance of providing HIV prevention options that are both effective and feasible given personal and social circumstances

Accuracy of Self-Report and Pill-Count Measures of Adherence in the FEM-PrEP Clinical Trial: Implications for Future HIV-Prevention Trials

Abstract Oral emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) has been evaluated as pre-exposure prophylaxis (PrEP). We describe the accuracy of self-reported adherence to FTC/TDF and pill counts when compared to drug concentrations in the FEM-PrEP trial. Using drug concentrations of plasma tenofovir (TFV) and intracellular tenofovir diphosphate (TFVdp) among a random sub-sample of 150 participants assigned to FTC/TDF, we estimated the positive predictive value (PPV) of four adherence measures. We also assessed factors associated with misreporting of adherence using multiple drug-concentration thresholds and explored pill use and misreporting using semi-structured interviews (SSIs). Reporting use of C1 pill in the previous 7 days had the highest PPV, while pill-count data consistent with missing B1 day had the lowest PPV. However, all four measures demonstrated poor PPV. Reported use of oral contraceptives (OR 2.26; p = 0.014) and weeks of time in the study (OR 1.02; p \ 0.001) were significantly associated with misreporting adherence. Although most SSI participants said they did not misreport adherence, participant-dependent adherence measures were clearly unreliable in the FEM-PrEP trial. Pharmacokinetic monitoring remains the measure of choice until more reliable participant-dependent measures are developed

Bivariate regression of demographic factors associated with having sex without a condom with a primary partner ⁺.

+<p>Versus always using a condom during sex in last 4 weeks. Sample includes only those who reported vaginal sex with a primary partner in the last 4 weeks and those who responded to condom use question.</p>1<p>With each increase of a year.</p>2<p>Response is “yes” versus “no”.</p><p>Bivariate regression of demographic factors associated with having sex without a condom with a primary partner ^{<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0106410#nt117" target="_blank">+</a>}.</p

Baseline Demographics.

<p>*Data presented are n (%) unless specified.</p><p>Baseline Demographics.</p

Bivariate logistic regression of demographic factors associated with having more than one sexual partner⁺.

+<p>Versus having a primary partner only. Sample includes only those who reported having a primary partner only or more than one sexual partner.</p>1<p>With each increase of a year.</p>2<p>Response is “yes” versus “no”.</p><p>Bivariate logistic regression of demographic factors associated with having more than one sexual partner^{<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0106410#nt114" target="_blank">+</a>}.</p