Adesão à profilaxia pré-exposição em homens que fazem sexo com homens (hsh) e mulheres transexuais em risco de contrair HIV

Background: In a concentrated epidemic, HIV spreads rapidly in one or more specific subpopulations, with relatively modest spread in the general population. In Latin America, some key population such as gays, bisexuals and other men who have sex with men (MSM) and transgender women (TGW) are disproportionately affected by HIV/AIDS, a trend that is becoming stronger in recent years. Pree-exposure Prophylaxis (PrEP) is based on the use of antiretroviral (ARV) drugs to prevent HIV acquisition. The daily oral use of emtricitabine and tenofovir disoproxil fumarate (FTC/TDF) is effective for PrEP and has been available in the Brazilian Public Health System (SUS) since December 2017. Studies have demonstrated a strong association between pharmacological levels of FTC/TDF in plasma or inside the cells and protection against HIV acquisition, achieving 97-100% protection when levels of adherence are achieved. Objectives: To describe patterns and correlations of adherence to PrEP among MSM and TGW in a demonstration project (PrEP Brasil); evaluate the effectiveness of text messages (SMS) in adherence to PrEP; evaluate self-reported adherence to PrEP and its perceived barriers and facilitators. First Manuscript: To evaluate the concordance between three indirect adherence measures (medication possession ratio or MPR, pill count and self-report) and highly protective drug levels measured by dried blood spot (DBS) among participants retained through 48 weeks in the PrEP Brasil Study. Tenofovir diphosphate (TFV-DP) concentration in DBS was measured at week 48. Areas under the curve (AUC) were used to evaluate the concordance between achieving protective levels of TFV-DP (\2265700fmol/punch) and the indirect adherence measures. Youden\2019s index and distance to corner were used to determine the optimal cutoff points for each indirect adherence measure. Sensitivity, specificity, negative (NPV) and positive (PPV) predictive values were calculated for the each cutoff points. Finally, Delong test was used to compare AUCs. All indirect adherence measures discriminated between participants with and without protective drug levels (AUC>0.5). High adherence was predictive of protective levels (PPV>0.8) while low adherence was not predictive of lack of protective levels (NPV<0.5). No significant differences were found among the adherence methods (p=0.44). Second Manuscript: To evaluate the effectiveness of SMS in improving adherence to daily FTC/TDF use during the PrEP Brasil study. An interactive SMS pilot sub-study was offered to all participants on the screening visit. Subjects who agreed to participate were randomized 1: 1 to receive only standard care (SoC), which included adherence counseling, or intervention (SMS). SMS was sent weekly to participants at a predetermined time. Adequate adherence to PrEP was defined as having MPR \2265 1.02, which was the best cutoff point for reaching protective levels of TFV-DP at weeks 4 and 48. Generalized Estimation Equations (GEE) were used to access factors associated with adequate adherence to PrEP. Of the 450 participants included in PrEP Brasil, 417 (92.7%) were randomized in the sub-study: 210 in the SoC arm and 207 in the SMS arm. A total of 347 (83.2%) participants completed the study, and receiving SMS did not increase retention at week 48. A higher proportion of participants in the group receiving SMS showed adequate adherence to PrEP throughout the study. In multivariate analysis, receiving SMS was a predictor of adequate adherence to PrEP (AOR = 1.37; 95% CI: 1.07-1.75) when adjusted for visit, location, age, receptive anal sex without condom and alcohol use. Third Manuscript: To evaluate self-reported PrEP adherence (30-days recall) and its perceived barriers and facilitators among participants retained through 48 weeks in the PrEP Brasil study. Logistic regression was used to evaluate predictors for optimal adherence (=100%). Median adherence in the past 30-days was 100%(IQR:92-100); 60.6% participants (205/338) reported optimal adherence. Most (82.2%; 278/338) reported not having difficulty with taking FTC/TDF and 81.3% (274/338) reported excellent or very good ability. Perceived barriers and facilitators were reported by 38.2%(129/338) and 98.5%(333/338), respectively; main facilitators to PrEP use included associating with some daily activity (59%), being engaged with PrEP (49%), keeping the tablets in some visible place and carrying the medication with them (45%), use of alarm (39%), fear of becoming HIV infected (38%). The main barriers to PrEP use included forgetting doses (50%), change in daily rotine (38%), pills shortage (25%) and not having the pill at time of dose (12%). Reported difficulties due to drug or alcohol use, no HIV perceived risk, privacy issues or side effects were uncommon (\226410%). In multivariate analysis, being from Rio de Janeiro, TGW, stimulant use and having perceived barriers to PrEP use were associated with decreased odds of optimal adherence. Conclusions: High adherence levels measured by different indirect methods (pill count, MPR and self-report) were verified at week 48 and all methods were able to discriminate participants who achieved or not protective levels of tenofovir. The SMS intervention was effective in improving adherence and PrEP coverage throughout the study, but had no impact on retention at week 48. Our findings provide information for designing, reinforcing, and updating strategies for improving adherence, and for developing best practices for promoting adherence to PrEP in our context.