Adesão e descontinuidade da profilaxia pré-exposição ao HIV (PrEP) entre adolescentes homens que fazem sexo com homens, travestis e mulheres transexuais no Brasil.

Abstract

Background: Since 2017, daily oral PrEP has been offered for free by the Brazilian National Health System, and in 2022, it was extended to adolescents from 15 years of age who are sexually active and at increased risk of acquiring HIV infection. To ensure effectiveness in the implementation of PrEP, it is essential to have accurate tools that provide information to identify adolescents who need additional adherence support, as well as to identify individual, social, and programmatic factors that may lead to early PrEP discontinuation. Objectives: 1) To summarize the evidence on measures for monitoring PrEP adherence; 2) To evaluate the performance of indirect adherence measures among men who have sex with men (MSM) and transgender women (TGW) in Brazil; 3) To study factors associated with PrEP discontinuation among MSM and TGW in the PrEP1519 cohort in Brazil. Methods: Three articles were developed to address the objectives of the thesis: 1) A systematic review of studies evaluating the performance of adherence measures to PrEP was conducted. Studies involving individuals without HIV infection who used daily oral PrEP with tenofovir disoproxil fumarate and emtricitabine (TDF/FTC) were included. The reference standard was the quantification of PrEP in dried blood spots (DBS) or plasma. The following indirect measures were assessed: self-report, pill count, pharmacy records, and electronic monitoring. Bias risk was assessed using the QUADAS-2 tool. 2) This is a diagnostic accuracy study using data from the PrEP1519 study, the first PrEP demonstrative cohort that included adolescent cisgender men who have sex with men (AMSM) and transgender women (ATrMT) aged 15 to 19 years in three Brazilian cities: Salvador, Belo Horizonte, and São Paulo. The reference standard was the concentration of tenofovir-diphosphate (TFV-DP) in DBS. Three indirect measures were evaluated: medication possession ratio (MPR), pill count, and self-report. The area under the curve (AUC) was calculated for protective TFV-DP levels (≥800 fmol/punch). Sensitivity (SE) and specificity (SP) were calculated for established cutoff points. 3) A cohort study was conducted with adolescents who initiated PrEP in the PrEP1519 study. PrEP discontinuation was defined not being in PrEP possession for more than 90 days. Kaplan-Meier curves were used to analyze the probabilities of discontinuation. Cox regression was employed to estimate adjusted Hazard Ratios (aHR) with 95% confidence intervals (95% CI). Results: 1) The review included 16 articles. Risk of bias assessment showed that most studies had a low risk of bias. The study found high variability among adherence measures, with self-report being the most commonly used method. 2) TFV-DP quantification was performed on 302 DBS samples from 188 participants. The AUC was 0.59 for MPR, 0.69 for pill count, and 0.75 for self-report. Combining MPR and self-report increased the AUC to 0.77. The Youden index identified cutoff points of 0.91 for MPR, 83.3% for self-report, and 58.7% for pill count, with corresponding sensitivities of 0.80, 0.97, and 0.92, and specificities of 0.40, 0.46, and 0.38. For cutoff points equivalent to 7-day use, the specificities were 0.57, 0.80, and 0.91, respectively. 3)Among 829 adolescents who initiated PrEP, the discontinuation incidence rate was 75.6 per100 person-years. The probability of discontinuation was 52.61% in the first year. In themultivariate analysis, transgender adolescents (aHR: 1.63; 95% CI: 1.23 - 2.16) andadolescents with medium perceived risk (aHR: 1.29; 95% CI: 1.02 - 1.64) or low perceivedrisk (aHR: 1.65; 95% CI: 1.29 – 2.12) had a higher risk of discontinuation, while adolescentswith a partner living with HIV had a lower risk of discontinuation (aHR: 0.57; 95% CI: 0.35 –0.91). Conclusions: This thesis presents important contributions to monitoring PrEP adherenceamong key population adolescents. Indirect measures can be easily implemented into routineclinical practice and represent an alternative to direct measures of PrEP adherence, particularlyin resource-limited settings, while considering their limitations in identifying adolescents withlow adherence. The combination of measures provides more accurate information. In addition,the PrEP discontinuation rate among adolescents is high, associated with risk perception andthe vulnerability of transgender women. PrEP implementation in adolescents should beaccompanied by effective strategies for adherence monitoring and addressing factors that maycontribute to discontinuation.