Estradiol and Spironolactone Plasma Pharmacokinetics Among Brazilian Transgender Women Using HIV Pre-Exposure Prophylaxis: Analysis of Potential Interactions.

BACKGROUND AND OBJECTIVE: An important barrier to HIV prevention among transgender women (TGW) is the concern that oral pre-exposure prophylaxis (PrEP) negatively affects the efficacy of feminizing hormone therapy (FHT). We aimed to assess the impact of PrEP on FHT pharmacokinetics (PK) among TGW from Brazil. METHODS: We performed a drug-drug interaction sub-study among TGW enrolled in a daily oral PrEP demonstration study (PrEParadas, NCT03220152). Participants had a first PK assessment (PK1) 15 days after FHT (estradiol valerate 2-6 mg plus spironolactone 100-200 mg) initiation and then started PrEP (tenofovir disoproxil fumarate 300 mg/emtricitabine 200 mg). A second PK evaluation was performed 12 weeks later (PK2). Blood samples were collected prior and after the directly observed dosing (0, 0.5, 1, 2, 4, 6, 8, and 24 hours). Pharmacokinetic parameters of estradiol, spironolactone, and metabolites were estimated by non-compartmental analysis (Monolix 2021R2, Lixoft®) and compared as geometric mean ratios (GMRs, 90% confidence interval [CI]). RESULTS: Among 19 TGW who completed the substudy, median age was 26 years (interquartile range: 23-27.5). Estradiol area under the plasma concentration-time curve (AUCτ) and trough concentrations did not differ between PK1 and PK2 evaluations (GMR [90% CI]: 0.89 [0.76-1.04] and 1.06 [0.94-1.20], respectively). Spironolactone and canrenone AUCτ were statistically lower at PK2 than PK1 (0.76 [0.65-0.89] and 0.85 [0.78-0.94], respectively). Canrenone maximum concentration was also lower at PK2 than PK1 (0.82 [0.74-0.91]). CONCLUSION: Estradiol PK was not influenced by PrEP concomitant use. The small differences observed in some spironolactone and canrenone PK parameters should not prevent the concomitant use of estradiol-based FHT and PrEP. TRIAL REGISTRATION: This trial (NCT03220152) was registered on July 18, 2017.

Impact of feminizing hormone therapy on tenofovir and emtricitabine plasma pharmacokinetics: a nested drug-drug interaction study in a cohort of Brazilian transgender women using HIV pre-exposure prophylaxis.

OBJECTIVES: Potential interactions between feminizing hormone therapy (FHT) and pre-exposure prophylaxis (PrEP) may be a barrier to PrEP use among transgender women (TGW). We aimed to assess the impact of FHT on PrEP plasma pharmacokinetics (PK) among TGW. METHODS: This was a PK substudy of the effects of FHT on tenofovir disoproxil fumarate/emtricitabine nested to a trans-specific PrEP demonstration study (NCT03220152). Participants were assigned to receive PrEP only (noFHT) or standardized FHT (sFHT; oestradiol valerate 2-6 mg plus spironolactone 100-300 mg) plus PrEP for 12 weeks, after which they could start any FHT (aFHT). Short- and long-term PK assessment occurred at Weeks 12 and 30-48, respectively (plasma samples prior and 0.5, 1, 2, 4, 6, 8 and 24 h after dose). Non-compartmental PK parameters of tenofovir and emtricitabine were compared as geometric mean ratios (GMRs) between noFHT and PrEP and FHT (sFHT at short-term PK; aFHT at long-term PK) participants. RESULTS: No differences in tenofovir and emtricitabine plasma PK parameters were observed between the short-term PK of noFHT (n = 12) and sFHT participants (n = 18), except for emtricitabine Cmax [GMR: 1.15 (95% CI: 1.01-1.32)], or between noFHT short-term PK and aFHT long-term PK (n = 13). Most participants were on oestradiol valerate 2 mg at the short-term PK (56%) and 4 mg at the long-term PK (54%). Median (IQR) oestradiol levels were 56.8 (43.2-65.4) pg/mL at short-term PK (sFHT) and 44.8 (24.70-57.30) pg/mL at long-term PK (aFHT). No participants in this analysis seroconverted during the study. CONCLUSIONS: Our results indicate no interaction of FHT on tenofovir levels, further supporting PrEP use among TGW using FHT.

High prevalence of anal high-risk HPV infection among transwomen: estimates from a Brazilian RDS study.

INTRODUCTION: As the leading sexually transmitted infection worldwide, human papillomavirus (HPV) may disproportionately affect transwomen. We aimed to estimate anal HPV prevalence, especially focusing on high-risk (hr)-HPV types and evaluate their associated factors among transwomen living in Rio de Janeiro, Brazil. METHODS: Transwomen enrolled in a respondent-driven sampling (RDS)-based survey conducted between August 2015 and January 2016 self-collected anal samples, which were promptly stored at minus 80°C. After DNA extraction, HPV detection and genotyping were performed using the PapilloCheck test. We estimated HPV prevalences and evaluated the correlates of anal hr-HPV infection using a regression logistic model. RESULTS: Out of 345 transwomen, 272 (78.8%) were included in this analysis (122 [44.9%] HIV-positive). No participant had ever received HPV vaccination. Among participants enrolled, 212 (77.9%) were positive for any anal HPV type and 165 (60.7%) for hr-HPV. Most common hr-HPV were as follows: HPV16 (17.6%), HPV68 (14.7%), HPV39 (14.3%), HPV56 (12.5%), HPV51 (11.4%) and HPV52 (11.0%). HIV-positive transwomen had three times the odds of having an hr-HPV compared to HIV-negative transwomen. Participants who had a current rectal Neisseria gonorrhoeae infection had 3.7 times the odds of being coinfected with hr-HPV. Among HIV-positive transwomen, neither antiretroviral therapy use, undetectable viral load, current and nadir CD4 counts were associated with anal hr-HPV infection. CONCLUSIONS: Brazilian transwomen in our study exhibit some of the highest population-specific rates of HPV and hr-HPV. There is an urgent need to elucidate the burden of HPV infection, prevalence of HPV-related diseases and access to and uptake of HPV vaccination among transwomen, especially from low- and middle-income settings.

Transcendendo: A Cohort Study of HIV-Infected and Uninfected Transgender Women in Rio de Janeiro, Brazil.

Purpose: Worldwide, the burden of adverse health conditions is substantial among travestis and transgender women (trans women). Transcendendo, the first trans-specific cohort in a low- or middle-income country, is an open cohort established in August 2015 to longitudinally evaluate the health aspects of trans women aged ≥18 years in Rio de Janeiro, Brazil. Methods: Study visits occur on an annual basis. Data on sociodemographics, behavioral, gender transition, affirmation procedures, hormone use, discrimination, violence, clinical and mental health, HIV prevention, and care (for those HIV-infected) are collected. Physical examination, anthropometric measurements, and laboratory tests are performed. Results: As of July 2017, 322 trans women were enrolled in the cohort with a median age of 31.5 years (interquartile range 25.7-39.5), of whom 174 (54%) were HIV-infected. The Transcendendo baseline information reinforces the scenario of marginalization and deprivation surrounding trans women. Most participants had low income (62.0% were living with below US$ 10.00/day), showed a very high engagement in sex work (78.6%), and reported increased occurrence of sexual (46.3%) and physical (54.0%) violence. Pre-exposure peophylaxis (PReP) was used by 18.8% of the HIV-uninfected trans women, only through research participation. Positive screening for depression (57.8%) and problematic use of tobacco (56.6%), cannabis (28.9%), cocaine (23.8%), and alcohol (21.5%) were high. Almost all participants (94.8%) reported hormone use at some point, mostly without medical supervision (78.7%). Conclusion: Our results describe a context of exclusion experienced by trans women, exposing vulnerabilities of this population in a middle-income country, with poor access to trans-specific care, HIV prevention and care, and mental health care. Addressing transgender experiences and needs can help the development of strategies to diminish stigma, improve health care environment, guide future research on trans morbidities, substance use, and trans-specific interventions to support health-related recommendations. Ultimately, it contributes to close the gaps concerning transgender health and reinforces that trans care cannot be disentangled from the social environment that surrounds trans women.

HIV testing and the care continuum among transgender women: population estimates from Rio de Janeiro, Brazil.

INTRODUCTION: Evidence suggests that, of all affected populations, transgender women (transwomen) may have the heaviest HIV burden worldwide. Little is known about HIV linkage and care outcomes for transwomen. We aimed to estimate population-level indicators of the HIV cascade of care continuum, and to evaluate factors associated with viral suppression among transwomen in Rio de Janeiro, Brazil. METHODS: We conducted a respondent-driven sampling (RDS) study of transwomen from August 2015 to January 2016 in Rio de Janeiro, Brazil and collected data on linkage and access to care, antiretroviral treatment and performed HIV viral load testing. We derived population-based estimates of cascade indicators using sampling weights and conducted RDS-weighted logistic regression analyses to evaluate correlates of viral suppression (viral load ≤50 copies/mL). RESULTS: Of the 345 transwomen included in the study, 89.2% (95% CI 55-100%) had been previously tested for HIV, 77.5% (95% CI 48.7-100%) had been previously diagnosed with HIV, 67.2% (95% CI 39.2-95.2) reported linkage to care, 62.2% (95% CI 35.4-88.9) were currently on ART and 35.4% (95% CI 9.5-61.4%) had an undetectable viral load. The final adjusted RDS-weighted logistic regression model for viral suppression indicated that those who self-identified as black (adjusted odds ratio [aOR] 0.06, 95% CI 0.01-0.53, p < 0.01), reported earning ≤U$160/month (aOR 0.11, 95% CI 0.16-0.87, p = 0.04) or reported unstable housing (aOR 0.08, 95% CI 0.01-0.43, p < 0.01) had significantly lower odds of viral suppression. CONCLUSIONS: Our cascade indicators for transwomen showed modest ART use and low viral suppression rates. Multi-level efforts including gender affirming care provision are urgently needed to decrease disparities in HIV clinical outcomes among transwomen and reduce secondary HIV transmission to their partners.