We conducted a prospective study of 13 heterosexual couples to understand the impact of recent condomless vaginal sex on vaginal immune marker measurement and potential exposure misclassification due to the presence of semen. All immune markers were detectable in semen and concentrations of vaginal immune markers varied by sex recency.

Problem Genital inflammatory changes may be a mechanism of increased HIV risk among injectable progestin‐only contraception ( IPC ) users. Method of Study We conducted a cross‐sectional analysis of 376 Kenyan and South African women. Genital cytokines and secretory leukocyte peptidase inhibitor concentrations in a reference population were compared to IPC users and women with reproductive tract infections. Results No significant variability in marker concentrations was observed by age or site. Depot medroxyprogesterone acetate ( DMPA ) users had significantly higher MIP ‐1α, MIP ‐1β, IL ‐6, IL ‐8, IP ‐10, and RANTES concentrations. Norethisterone oenanthate users had significantly higher IL ‐6, IL ‐8, and RANTES concentrations. Women with sexually transmitted infections had variable inflammation, and women with bacterial vaginosis exhibited a mixed profile of up and downregulation. Conclusion The finding of substantial mucosal inflammation among DMPA users provides evidence which, combined with the results of prior studies, suggests that DMPA may create an immune environment conducive to HIV target cell recruitment and inhibitory for antiviral activity.

OBJECTIVE:The objective was to assess associations between tenofovir disoproxil fumarate-emtricitabine (TDF-FTC) exposure and levonorgestrel (LNG) concentrations among Kenyan HIV prevention trial participants using Sino-implant (II) LNG implants for contraception.METHODS:Women were offered implants among other contraceptive methods, were randomized to daily TDF-FTC or placebo, and followed monthly up to 56weeks. Associations between TDF-FTC exposure and mean LNG values were analyzed with linear mixed models.RESULTS:Of 739 women, 29 (3.9%) received implants with no incident pregnancies and one discontinuation. Mean LNG concentrations over 56weeks among 28 women contributing data ranged between 214.0 and 659.8pg/mL with no significant difference between TDF-FTC and placebo arms or between variable levels of TDF-FTC adherence.CONCLUSION:Concomitant TDF-FTC use was not associated with a significant change in plasma LNG concentrations among women using Sino-implant (II) in the first year of use.

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 7 days had the highest PPV, while pill-count data consistent with missing ≤1 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.

Background: FEM-PrEP was unable to demonstrate the effectiveness of oral emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) as pre-exposure prophylaxis for HIV prevention because of low adherence. We hypothesized that one reason for the poor adherence was low perceived HIV risk. Methods: At enrollment and at quarterly follow-up visits, we assessed participants' perceived HIV risk for the subsequent 4 weeks. We used logistic regression to assess factors associated with some (small, moderate, or high) perceived HIV risk. We also used logistic regression with robust variance estimation to assess the association between risk perceptions (none versus some) reported at enrollment and at weeks 12, 24, and 36 and good adherence based on drug concentrations of plasma tenofovir and intracellular tenofovir diphosphate in specimens collected 4 weeks later (at weeks 4, 16, 28, and 40) among 150 randomly selected participants assigned FTC/TDF. Results: Multiple factors were statistically associated with having some perceived risk, including having sex without a condom, having multiple partners, and not knowing if a partner has HIV. We observed a significant association between having some risk perception and good adherence (odds ratio: 2.0; 95% confidence interval: 1.1 to 3.5; P = 0.016). Conclusions: Data suggest that participants are likely knowledgeable about factors that increase their HIV risk. Perceived risk seemed to have influenced some participants' decisions to adhere to the study pill within the context of a placebo-controlled clinical trial. Future research can explore the role of risk perception in the uptake of and adherence to pre-exposure prophylaxis, now that FTC/TDF has been shown efficacious.

Safety of tenofovir disoproxil fumarate/emtricitabine (TDF-FTC) has been studied more extensively among HIV-infected patients than among HIV-uninfected people. Using data from a pre-exposure trial – FEM-PrEP –, we determined the cumulative probabilities of grade 1+ ALT, AST and creatinine and grade 2+ phosphorus toxicities; ALT/AST toxicities by baseline hepatitis B status; and change in mean creatinine, phosphorus, ALT and AST levels controlling for TDF-FTC adherence.

BACKGROUND:Several clinical trials have demonstrated the safety and effectiveness of oral tenofovir disoproxil fumarate (TDF), with or without emtricitabine (FTC), as pre-exposure prophylaxis (PrEP) for reducing the risk of HIV acquisition. Adherence to the study product was insufficient to demonstrate the effectiveness of FTC/TDF in 2 PrEP clinical trials conducted among women (FEM-PrEP and the Vaginal and Oral Interventions to Control the Epidemic study), but further analyses of adherence in these studies may inform PrEP demonstration projects and future HIV prevention clinical trials. METHODS:We randomly selected a subcohort of 150 participants randomized to FTC/TDF in 3 FEM-PrEP sites (Bondo, Kenya; Bloemfontein, South Africa; and Pretoria, South Africa) to examine adherence levels over time and to assess factors associated with adherence, based on plasma tenofovir and intracellular tenofovir diphosphate drug concentrations in specimens collected at 4-week visit intervals. RESULTS:We observed drug concentrations consistent with good adherence in 28.5% of all visit intervals when drug was available to use, but only 12% of participants achieved good adherence throughout their study participation. In multivariate analysis, the Bloemfontein site [odds ratio (OR): 2.43; 95% confidence interval (CI): 1.32 to 4.48] and liking the pill color (OR: 2.93; 95% CI: 1.18 to 7.27) were positively associated with good adherence, whereas using oral contraceptive pills at enrollment was negatively associated with good adherence (OR: 0.37; 95% CI: 0.18 to 0.74). CONCLUSIONS:Most participants did not regularly adhere to the study product throughout their trial participation, although a small minority did. Few factors associated with good adherence to the study product were identified in FEM-PrEP.

Background: Several clinical trials have demonstrated the safety and effectiveness of oral tenofovir disoproxil fumarate (TDF), with or without emtricitabine (FTC), as pre-exposure prophylaxis (PrEP) for reducing the risk of HIV acquisition. Adherence to the study product was insufficient to demonstrate the effectiveness of FTC/TDF in 2 PrEP clinical trials conducted among women (FEM-PrEP and the Vaginal and Oral Interventions to Control the Epidemic study), but further analyses of adherence in these studies may inform PrEP demonstration projects and future HIV prevention clinical trials. Methods: We randomly selected a subcohort of 150 participants randomized to FTC/TDF in 3 FEM-PrEP sites (Bondo, Kenya; Bloemfontein, South Africa; and Pretoria, South Africa) to examine adherence levels over time and to assess factors associated with adherence, based on plasma tenofovir and intracellular tenofovir diphosphate drug concentrations in specimens collected at 4-week visit intervals. Results: We observed drug concentrations consistent with good adherence in 28.5% of all visit intervals when drug was available to use, but only 12% of participants achieved good adherence throughout their study participation. In multivariate analysis, the Bloemfontein site [odds ratio (OR): 2.43; 95% confidence interval (CI): 1.32 to 4.48] and liking the pill color (OR: 2.93; 95% CI: 1.18 to 7.27) were positively associated with good adherence, whereas using oral contraceptive pills at enrollment was negatively associated with good adherence (OR: 0.37; 95% CI: 0.18 to 0.74). Conclusions: Most participants did not regularly adhere to the study product throughout their trial participation, although a small minority did. Few factors associated with good adherence to the study product were identified in FEM-PrEP.

IntroductionRisk perception is a core construct in many behaviour change theories in public health. Individuals who believe they are at risk of acquiring an illness may be more likely to engage in behaviours to reduce that risk; those who do not feel at risk may be unlikely to engage in risk reduction behaviours. Among participants who seroconverted in two FEM‐PrEP sites – Bondo, Kenya, and Pretoria, South Africa – we explored perceived HIV risk and worry about acquiring HIV prior to HIV infection.MethodsFEM‐PrEP was a phase III clinical trial of once‐daily, oral emtricitabine and tenofovir disoproxil fumarate for HIV prevention among women in sub‐Saharan Africa. We asked all participants about their perceived HIV risk in the next four weeks, prior to HIV testing, during a quantitative face‐to‐face interview at enrolment and at quarterly follow‐up visits. Among participants who seroconverted, we calculated the frequencies of their responses from the visit conducted closest to, but before, HIV acquisition. Also among women who seroconverted, we conducted qualitative, semi‐structured interviews (SSIs) at weeks 1, 4 and 8 after participants’ HIV diagnosis visit to retrospectively explore feelings of HIV worry. Applied thematic analysis was used to analyse the SSI data.ResultsAmong participants who seroconverted in Bondo and Pretoria, 52% reported in the quantitative interview that they had no chance of acquiring HIV in the next four weeks. We identified four processes of risk rationalization from the SSI narratives. In “protective behaviour,” participants described at least one risk reduction behaviour they used to reduce their HIV risk; these actions made them feel not vulnerable to HIV, and therefore they did not worry about acquiring the virus. In “protective reasoning,” participants considered their HIV risk but rationalized, based on certain events or beliefs, that they were not vulnerable and therefore did not worry about getting HIV. In “recognition of vulnerability,” participants described reasons for being worried about getting HIV but said no or limited action was taken to reduce their perceived vulnerability. Participants with “no rationalization or action” did not describe any HIV worry or did not engage in HIV risk reduction behaviours.ConclusionsWomen who are at substantial risk of acquiring HIV may underestimate their actual risk. Yet, others who accurately understand their HIV risk may be unable to act on their concerns. Perceived HIV risk and risk rationalization are important concepts to explore in risk reduction counselling to increase the use of HIV prevention strategies among women at risk of HIV.

Background: 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.Objective: To describe and compare the sexual risk context of the study population from two FEM-PrEP trial sites-Bondo, Kenya, and Pretoria, South Africa.Methods: 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).Results: 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.Discussion: 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.