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.

A Peer-Led Digital Intervention to Reduce HIV Prevention and Care Disparities Among Young Brazilian Transgender Women (The BeT Study): Protocol for an Intervention Study.

BACKGROUND: The HIV epidemic continues to disproportionately burden marginalized populations despite the availability of effective preventive and therapeutic interventions. Transgender women are severely affected by HIV worldwide including in Brazil and other low- and middle-income countries, with evidence of increasing new infections among young people. There is an urgent need for youth-specific HIV prevention and care interventions for young transgender women in Brazil. OBJECTIVE: This study aims to (1) address stigma in the Brazilian public health system and (2) reduce barriers to HIV care and prevention with systems navigation among young transgender women aged 18-24 years in Rio de Janeiro, Brazil. METHODS: The Brilhar e Transcender (BeT) study is a status-neutral, peer-led, single-arm digital intervention study enrolling 150 young transgender women in Rio de Janeiro, Brazil. The intervention was pilot tested and refined using data from a formative phase. The BeT intervention takes place over 3 months, is delivered remotely via mobile phone and in person by peers, and comprises three components: (1) BeT sessions, (2) digital interactions, and (3) automated messages. Eligibility criteria include identifying as transgender women, being aged 18-24 years, speaking in Portuguese, and living in the Rio de Janeiro metropolitan area in Brazil. The primary outcomes are HIV incidence, pre-exposure prophylaxis uptake, linkage to HIV care, and viral suppression. Primary outcomes were assessed at baseline and quarterly for 12 months. Participants respond to interviewer-based surveys and receive tests for HIV and sexually transmitted infections. RESULTS: The study has been approved by the Brazilian and the US local institutional review boards in accordance with all applicable regulations. Study recruitment began in February 2022 and was completed in early July 2022. Plans are to complete the follow-up assessment of study participants on July 2023, analyze the study data, and disseminate intervention results by December 2023. CONCLUSIONS: Interventions to engage a new generation of transgender women in HIV prevention and care are needed to curb the epidemic. The BeT study will evaluate a digital peer-led intervention for young transgender women in Brazil, which builds on ways young people engage in systems and uses peer-led support to empower transgender youth in self-care and health promotion. A promising evaluation of the BeT intervention may lead to the availability of this rapidly scalable status-neutral HIV intervention that can be translated throughout Brazil and other low- and middle-income countries for young transgender women at high risk of or living with HIV. TRIAL REGISTRATION: ClinicalTrials.gov NCT05299645; https://clinicaltrials.gov/ct2/show/NCT05299645. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/44157.

Comparing Web-Based Venues to Recruit Gay, Bisexual, and Other Cisgender Men Who Have Sex With Men to a Large HIV Prevention Service in Brazil: Evaluation Study.

BACKGROUND: Internet and mobile phones, widely available in Brazil, could be used to disseminate information about HIV prevention and to recruit gay, bisexual, and other cisgender men who have sex with men (MSM) to HIV prevention services. Data evaluating the characteristics of MSM recruited through different web-based strategies and estimating their cost and yield in the country are not available. OBJECTIVE: We aimed to describe a web-based recruitment cascade, compare the characteristics of MSM recruited to a large HIV prevention service in Rio de Janeiro according to web-based venues, and estimate the cost per participant for each strategy. METHODS: We promoted advertisements on geosocial networking (GSN) apps (Hornet and Grindr) and social media (Facebook and Instagram) from March 2018 to October 2019. The advertisements invited viewers to contact a peer educator to schedule a visit at the HIV prevention service. Performance of web-based recruitment cascade was based on how many MSM (1) were reached by the advertisement, (2) contacted the peer educator, and (3) attended the service. We used chi-square tests to compare MSM recruited through GSN apps and social media. The estimated advertisement cost to recruit a participant was calculated by dividing total advertisement costs by number of participants who attended the service or initiated preexposure prophylaxis (PrEP). RESULTS: Advertisement reached 1,477,344 individuals; 1270 MSM contacted the peer educator (86 contacts per 100,000 views)-564 (44.4%), 401 (31.6%) and 305 (24.0%)-through social media, Grindr, and Hornet. Among the 1270 individuals who contacted the peer educator, 36.3% (n=461) attended the service with similar proportion for each web-based strategy (social media: 203/564, 36.0%; Grindr: 152/401, 37.9%; and Hornet: 107/305, 35.1%). MSM recruited through GSN apps were older (mean age 30 years vs 26 years; P<.001), more frequently self-reported as White (111/247, 44.9% vs 62/191, 32.5%; P=.03), and had higher schooling level (postsecondary: 157/254, 61.8% vs 94/194, 48.5%; P=.007) than MSM recruited through social media. GSN apps recruited MSM with higher HIV risk as measured by PrEP eligibility (207/239, 86.6% vs 133/185, 71.9%; P<.001) compared with social media, but there was no difference in PrEP uptake between the two strategies (P=.22). The estimated advertisement costs per participant attending the HIV prevention service were US $28.36 for GSN apps and US $12.17 for social media. The estimated advertisement costs per participant engaging on PrEP were US $58.77 for GSN apps and US $27.75 for social media. CONCLUSIONS: Social media and GSN app advertisements were useful to disseminate information on HIV prevention strategies and to recruit MSM to a large HIV prevention service in Brazil. Compared to GSN apps, social media advertisements were less expensive and reached more vulnerable and younger MSM. Digital marketing campaigns should use different and complementary web-based venues to reach a plurality of MSM.

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.

Low PrEP adherence despite high retention among transgender women in Brazil: the PrEParadas study.

INTRODUCTION: We aimed to evaluate daily oral pre-exposure prophylaxis (PrEP) uptake, retention, and adherence and predictors of study non-attendance and low PrEP adherence in a Brazilian trans-specific 48-week study (PrEParadas). METHODS: We enrolled transgender women (TGW) engaging in high-risk sexual behaviours between August 2017 and December 2018. PrEP adherence was based on tenofovir diphosphate concentrations in dried blood spots (DBS). We used random effects logistic regression models and ordinal models to estimate the odds of having a missed visit and of low PrEP adherence, respectively. Multivariable models were adjusted for variables with p-value<0.10 in the univariate analysis. RESULTS: From the 271 eligible, 130 participants were enrolled in the study (PrEP uptake: 48%), out of which 111 (85.4%) were retained at 48 weeks. Multivariable model for study non-attendance included study visit, age, main sexual partner and stimulant use. The odds of missing a visit increased after the week 24. Participants aged 18-24 (adjusted odds ratio [aOR] = 8.76, 95% CI: 2.09-36.7) and 25-34 years (aOR = 6.79, 95% CI: 1.72-26.8) compared to TGW aged 35+ years had significantly higher odds of having a missed visit. The odds of a missed visit were higher among participants reporting stimulant use (aOR = 4.99, 95% CI: 1.37-18.1) compared to no stimulant use. DBS levels at week 48 showed that 42 (38.5%), 14 (12.8%) and 53 (48.6%) of 109 participants had low, moderate and high PrEP adherence. Multivariable model for low PrEP adherence included study visit, age, schooling, race/colour, housing, binge drinking, stimulant use, feminizing hormone therapy (FHT) use and received text message. Low PrEP adherence was significantly higher among participants with less years of schooling (aOR = 6.71, 95% CI: 1.30-34.5) and had a borderline association with Black colour/race (aOR = 6.72, 95% CI: 0.94-47.8). Participants using the FHT available at the site had decreased odds of low PrEP adherence (aOR = 0.38, 95% CI: 0.16-0.88). No participant seroconverted over the course of the study. CONCLUSIONS: Although high PrEP retention can be achieved in a gender-affirming setting, PrEP adherence may be an important challenge faced among TGW due to social disparities. The scale-up of prevention tools like PrEP will have to address systemic social determinants as these stand as important barriers for TGW's access to health services.

Complementary Recruitment Strategies to Reach Men Who Have Sex with Men and Transgender Women: The Experience of a Large Brazilian HIV Prevention Service.

Different strategies have been used to reach men who have sex with men (MSM) and transgender women (TGW) for HIV prevention services. We described the characteristics of MSM and TGW attending a large HIV prevention service in Brazil according to different recruitment strategies or referrals. A total of 2713 individuals (2246[82.8%] MSM and 467[17.2%] TGW) attended the service. Among HIV-negative MSM and TGW, 74.6% and 82.8% were eligible for pre-exposure prophylaxis (PrEP), respectively. PrEP uptake among MSM and TGW was 56.4% and 39.1%, respectively. Participants were mostly referred by peers (43.6%), followed by web-based (24.1%) and venue-based recruitment (16.2%). More young and Black MSM were referred from venue-based recruitment, and web-based strategies more frequently referred MSM with higher education. TGW who were younger and had higher education were more frequently referred from venue-based recruitment. Web-based recruitment failed to reach TGW. Multiple strategies were complementary to reach diverse MSM and TGW populations.

RESUMEN: Diferentes estrategias se han usado para alcanzar hombres que tienen sexo con hombres (HSH) y mujeres trans (MT) en los servicios preventivos del VIH. Describimos las características de HSH y MT que acudieron a un servicio de prevención del VIH en Brasil, de acuerdo con diferentes estrategias de reclutamiento. Un total de 2713 personas (2246[82.8%] HSH y 467[17.2%] MT) asistieron al servicio y aquellos con resultado negativo al VIH (74.6% de HSH y 82.8% de MT) fueron candidatos a la profilaxis preexposición, siendo iniciada por 56.4% y 39.1%, respectivamente. Las referencias al servicio vinieron de pares (43.6%), en línea (24.1%) o por algún sitio (16.2%). Mayoritariamente los HSH jóvenes y negros, y las MT jóvenes con educación superior fueron referidos de algún sitio; mientras que los HSH con educación superior fueron en línea. Este último reclutamiento no sirvió para las MT. Múltiples estrategias fueron complementarias para alcanzar HSH y MT.

Prevalence and factors associated with suicidal behavior among trans women in Rio de Janeiro, Brazil.

BACKGROUND: Trans women face disproportionate burden of adverse health outcomes, including mental health issues. Very little is known about suicidal behavior among trans women in low- and middle-income settings, such as Brazil. We aimed to estimate the prevalence of lifetime suicidal behavior and to identify its associated factors among Brazilian trans women. METHODS: This was a cross-sectional study conducted among 345 trans women living in Rio de Janeiro, Brazil. We examined the prevalence of suicidal behavior (ideation and suicide attempt) and its associated factors using stepwise backward Poisson regression analysis with robust variance. RESULTS: Suicidal ideation was present among 47.25% of participants, and the prevalence of lifetime suicide attempt was 27.25%. Trans women with prior physical violence perpetrated by a family member had significantly higher prevalence of suicidal ideation (adjusted prevalence ratios [aPR]1.37), whereas those who reported sex work had lower prevalence ratio of suicidal ideation (aPR 0.76). Suicide attempt was significantly associated with living alone (aPR 1.48), physical violence by a casual partner (aPR 1.92), and sexual violence by a family member (aPR 1.69). Depression was significantly associated with both outcomes (aPR 1.90 for suicidal ideation and aPR 2.21 for suicide attempt). CONCLUSION: Suicidal behavior prevalence rates among Brazilian trans women were alarming and directly linked to violence and poor mental health. Effective mental health and public health policies addressing violence against trans women are urgently needed to prevent suicidal behavior among this highly vulnerable population.

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.

High risk and low HIV prevention behaviours in a new generation of young trans women in Brazil.

Adult trans women in Brazil are highly impacted by HIV, but little is known about risk for young trans women. Our study was conducted to compare the HIV prevalence and correlates of risk for young trans women ages 18-24 years old to adult trans women in Brazil. Trans women were recruited from Rio de Janeiro and Baixada (the metropolitan area of Rio de Janeiro), Brazil (N = 345). Youth ages 18-24 years of age had significantly greater odds of being HIV negative than adults (OR 0.4, 95% CI 0.2-0.6, p = 0.0002), but significantly lower odds of having post-exposure prophylaxis (PEP) knowledge (OR 0.5, 95% CI:0.3-0.9, p = 0.02) and PrEP awareness (OR 0.5, 95% CI: 0.3-0.8, p = 0.01). Young trans women also had significantly higher odds of using substances (OR 1.8, 95% CI 1.1-2.9, p = 0.02) and condomless anal intercourse with their last three sexual partners (OR 1.8, 95% CI: 1.1-3.0, p = 0.03) compared to adults. Already by age 24, one in four trans women in Brazil were infected with HIV pointing to a new generation at high risk of acquiring HIV. HIV prevention interventions are needed to change the healthcare system to reach and engage young trans women.

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.

Unveiling of HIV dynamics among transgender women: a respondent-driven sampling study in Rio de Janeiro, Brazil.

BACKGROUND: The burden of HIV in transgender women (transwomen) in Brazil remains unknown. We aimed to estimate HIV prevalence among transwomen in Rio de Janeiro and to identify predictors of newly diagnosed HIV infections. METHODS: We recruited transwomen from Rio de Janeiro, Brazil, by respondent-driven sampling. Eligibility criteria were self-identification as transwomen, being 18 years of age or older, living in Rio de Janeiro or its metropolitan area, and having a valid peer recruitment coupon. We recruited 12 seed participants from social movements and formative focus groups who then used peer recruitment coupons to refer subsequent peers to the study. We categorised participants as HIV negative, known HIV infected, or newly diagnosed as HIV infected. We assessed predictors of newly diagnosed HIV infections by comparing newly diagnosed with HIV-negative participants. We derived population estimates with the Respondent-Driven Sampling II estimator. FINDINGS: Between Aug 1, 2015, and Jan 29, 2016, we enrolled 345 eligible transwomen. 29·1% (95% CI 23·2-35·4) of participants had no previous HIV testing (adjusted from 60 participants), 31·2% (18·8-43·6) had HIV infections (adjusted from 141 participants), and 7·0% (0·0-15·9) were newly diagnosed as HIV infected (adjusted from 40 participants). We diagnosed syphilis in 28·9% (18·0-39·8) of participants, rectal chlamydia in 14·6% (5·4-23·8), and gonorrhoea in 13·5% (3·2-23·8). Newly diagnosed HIV infections were associated with black race (odds ratio 22·8 [95% CI 2·9-178·9]; p=0·003), travesti (34·1 [5·8-200·2]; p=0·0001) or transsexual woman (41·3 [6·3-271·2]; p=0·0001) gender identity, history of sex work (30·7 [3·5-267·3]; p=0·002), and history of sniffing cocaine (4·4 [1·4-14·1]; p=0·01). INTERPRETATION: Our results suggest that transwomen bear the largest burden of HIV among any population at risk in Brazil. The high proportion of HIV diagnosis among young participants points to the need for tailored long-term health-care and prevention services to curb the HIV epidemic and improve the quality of life of transwomen in Brazil. FUNDING: Brazilian Research Council, National Institute of Allergy and Infectious Diseases, Brazilian Sexually Transmitted Disease/AIDS, and Viral Hepatitis Department of the Brazilian Ministry of Health.