Transgender women, hormonal therapy and HIV treatment: a comprehensive review of the literature and recommendations for best practices

Abstract

IntroductionStudies have shown that transgender women (TGW) are disproportionately affected by HIV, with an estimated HIV prevalence of 19.1% among TGW worldwide. After receiving a diagnosis, HIV-positive TGW have challenges accessing effective HIV treatment, as demonstrated by lower rates of virologic suppression and higher HIV-related mortality. These adverse HIV outcomes have been attributed to the multiple sociocultural and structural barriers that negatively affect their engagement within the HIV care continuum. Guidelines for feminizing hormonal therapy among TGW recommend combinations of oestrogens and androgen blockers. Pharmacokinetic studies have shown that certain antiretroviral therapy (ART) agents, such as protease inhibitors (PIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs) and cobicistat, interact with ethinyl estradiol, the key oestrogen component of oral contraceptives (OCPs). The goal of this article is to provide an overview of hormonal regimens used by TGW, to summarize the known drug-drug interactions (DDIs) between feminizing hormonal regimens and ART, and to provide clinical care recommendations.MethodsThe authors identified English language articles examining DDIs between oestrogen therapy, androgen blockers and ART published between 1995 and 2015 using PubMed, Cumulative Index to Nursing and Allied Health Literature and EBSCOhost.Results and DiscussionPublished articles predominantly addressed interactions between ethinyl estradiol and NNRTIs and PIs. No studies examined interactions between ART and the types and doses of oestrogens found in feminizing regimens. DDIs that may have the potential to result in loss of virologic suppression included ethinyl estradiol and amprenavir, unboosted fosamprenavir and stavudine. No clinically significant DDIs were noted with other anti-retroviral agents or androgen blockersConclusionsThere are insufficient data to address DDIs between ART and feminizing hormone regimens used by TGW. There is an urgent need for further research in this area, specifically pharmacokinetic studies to study the direction and degree of interactions between oral, injectable and transdermal estradiol and ART. Clinicians need to be vigilant about possible interactions and monitor hormone levels if concerns arise. More research is also needed on the provision of hormone therapy and gender-affirming care on the long-term health outcomes of HIV-positive TGW.

Characterizing the HIV Prevention and Care Continua in a Sample of Transgender Youth in the U.S.

“…The levels of engagement in care and viral suppression reported in this sample of TF youth is similar to that of TF adults sampled in San Francisco [29], yet suboptimal relative UNAIDS 90-90-90 targets [75]. Consistent with research conducted in TG adults [28, 42, 76], medication adherence and retention in care were also suboptimal as only 55.0% of those currently taking medications had been adherent in the past 7 days and 33.9% had missed one or more HIV care appointment in the past 6 months. Additionally, in multivariable models, medical gender affirmation was associated with reduced odds of virological suppression and with increased odds of missing appointments.…”

“…Despite reports of sexual risk and substance use behaviors, low rates of PrEP uptake among HIV-uninfected TG youth in the sample were found. While initial engagement in care was high for TG youth living with HIV (83.9%), medication adherence (55.0%), retention in care (66.1%), and viral suppression (65.6%) rates were suboptimal, yet comparable to other studies of people living with HIV, including youth [67], cisgender adults [68–71], and TG adults [1, 42]. Determinants of engagement in the HIV prevention continuum were older age, being a youth of color, having a history of homelessness, and gender affirmation and stigma in primary HIV prevention settings.…”

“…Medical gender affirmation has been shown to improve psychological health and quality of life for TG individuals [32, 33], including for TG adolescents and emerging adults [34–36]. Several studies have considered medical gender affirmation in HIV-related outcomes for TG people [26, 37–42]; in general, medical gender affirmation (e.g., hormones) has been shown to positively increase retention in HIV care for TF living with HIV. Medical gender affirmation data on the full range of TG youth (e.g., TF, TM, nonbinary) across the HIV prevention and continua are lacking.…”

Transgender Women Living with HIV Frequently Take Antiretroviral Therapy and/or Feminizing Hormone Therapy Differently Than Prescribed Due to Drug–Drug Interaction Concerns

“…Thus, there are insufficient data to fully understand the risk of DDIs between ART and HT for TW. 23 However, even relatively minor or rare interactions warrant attention, as both HT and ART may be longterm or lifelong medications. In addition, TW living with HT and/or ART taken differently than prescribed due to DDI concern (n = 43)…”

What's in a Guideline? Developing Collaborative and Sound Research Designs that Substantiate Best Practice Recommendations for Transgender Health Care

“…There are also few studies investigating potential drug-drug interactions between the formulations of estrogens commonly used in some medically assisted gender transition and other drugs like those used for the treatment or pre-exposure prophylaxis of HIV infection or hepatitis C [26]. Although some studies, mostly small and cross-sectional in design, have suggested that mental health is improved by gender-affirming care [27,28], larger longitudinal studies on mental health and quality-of-life outcomes are needed to inform policies that would support making gender-affirming care more available and accessible and to develop best practices for the delivery of such care [29].…”