Elsevier

The Lancet HIV

Volume 2, Issue 12, December 2015, Pages e512-e519
The Lancet HIV

Articles
HIV pre-exposure prophylaxis in transgender women: a subgroup analysis of the iPrEx trial

https://doi.org/10.1016/S2352-3018(15)00206-4Get rights and content

Summary

Background

Pre-exposure prophylaxis (PrEP) with oral emtricitabine and tenofovir disoproxil fumarate is used to prevent the sexual acquisition of HIV in groups at high risk such as transgender women. We used data from the iPrEx study to assess PrEP efficacy, effectiveness, and adherence in transgender women.

Methods

The iPrEx trial was a randomised controlled trial of PrEP with oral emtricitabine plus tenofovir disoproxil fumarate compared with placebo in men who have sex with men (MSM) and transgender women, followed by an open-label extension. Drug concentrations were measured in blood by liquid chromatography and tandem mass spectroscopy. We did unplanned exploratory analyses to investigate differences in PrEP outcomes among transgender women and between transgender women and MSM.

Findings

Of the 2499 participants enrolled in the randomised controlled trial, 29 (1%) identified as women, 296 (12%) identified as trans, 14 (1%) identified as men but reported use of feminising hormones, such that 339 (14%) reported one or more characteristics and are classified as transgender women for the purpose of this study. Compared with MSM, transgender women more frequently reported transactional sex, receptive anal intercourse without a condom, or more than five partners in the past 3 months. Among transgender women, there were 11 HIV infections in the PrEP group and ten in the placebo group (hazard ratio 1·1, 95% CI 0·5–2·7). In the PrEP group, drug was detected in none of the transgender women at the seroconversion visit, six (18%) of 33 seronegative transgender women (p=0·31), and 58 (52%) of 111 seronegative MSM (p<0·0001). PrEP use was not linked to behavioural indicators of HIV risk among transgender women, whereas MSM at highest risk were more adherent.

Interpretation

PrEP seems to be effective in preventing HIV acquisition in transgender women when taken, but there seem to be barriers to adherence, particularly among those at the most risk. Studies of PrEP use in transgender women populations should be designed and tailored specifically for this population, rather than adapted from or subsumed into studies of MSM.

Funding

US National Institutes of Health and the Bill & Melinda Gates Foundation.

Introduction

Transgender refers to a person whose gender identity differs from their assigned birth sex.1 Although regional and national data on transgender populations are not available, a recent state-wide Massachusetts telephone survey found that 0·5% of respondents identified as transgender.2 Because of incomplete or inconsistent collection of gender identity data (such as birth sex and current gender identity), transgender people's participation in research is frequently obscured.3, 4

The prevalence of HIV infection is high in transgender communities.5 A 2008 meta-analysis of 22 regional US studies that did report HIV infection rates for transgender women found a laboratory-confirmed prevalence of 27·7% and self-reported prevalence of 11·8%.6 In 2011, the US Centers for Disease Control and Prevention (CDC) reported that transgender women have the highest percentage of new HIV diagnosis in CDC-funded testing progammes (2·1%, compared with 1·2% in non-transgender men and 0·4% in non-transgender women).7 A 2013 meta-analysis of data from 15 countries found an estimated HIV prevalence of 19·1% among transgender women, with an odds ratio (OR) of 49 in comparison with the general adult population.5

Many transgender women face structural barriers that contribute to the disproportionate burden of HIV, including inadequate legal protections against discrimination, and resulting insecurities in income, food, and housing.8, 9 PrEP research has primarily focused on men who have sex with men (MSM).10 Research and services adapted for transgender populations include staff training and procedures for ensuring gender affirmation and provision of gender affirming hormone therapy.

No evidence-based HIV prevention interventions designed specifically for transgender women exist. PrEP acceptability studies have typically included few transgender women, with no consideration for the sociocultural (and perhaps anatomical) differences from MSM.11, 12 Guidelines might assume similar practices and efficacies in MSM and transgender populations. For example, WHO guidelines in 2014 provide no specific considerations for the provision of PrEP to transgender women;13 CDC guidelines for PrEP implementation make no mention of this group;14 and PrEP demonstration projects have reported low or unclear levels of enrolment.15

Research in context

Evidence before this study

On Sept 18, 2015, we searched PubMed and conference abstracts for information about pre-exposure prophylaxis (PrEP) among transgender women with the term “transgender women and HIV and prevention” without language or date restrictions. Transgender women carry a disproportionate burden of the HIV epidemic and differ from men who have sex with men (MSM) with respect to their social situation, sexual practices, use of feminising hormones, and genital anatomy. Transgender women were included with MSM in many PrEP trials and demonstration projects, although the numbers of transgender participants has been low or unclear. A separate analysis of PrEP safety and efficacy among transgender women has not been reported. US Centers for Disease and Control recommendations for PrEP do not mention transgender women.

Added value of this study

This study presents the first separate analysis of transgender women who received oral emtricitabine plus tenofovir disoproxil fumarate PrEP in a randomised controlled trial and during an open-label extension. Compared with MSM, 339 transgender women had lower drug exposure and less consistent PrEP use over time, especially in situations conferring greater exposure to HIV. The relation between high drug concentrations and low HIV incidence were similar among MSM and transgender women. No transgender women who had drug concentrations suggesting use of four or more PrEP tablets per week acquired HIV. Bone mineral density tended to be less affected by PrEP among transgender women than in MSM, which might show less use of PrEP or a protective effect of feminising hormones. There was no evidence of liver toxicity.

Implications of all the available evidence

More information is needed about interactions between feminising hormones and PrEP medications, and the relation between PrEP use and drug concentrations among transgender women. Better ways to foster effective use of PrEP among transgender women are needed, and might arise from community support groups and programmes that integrate PrEP with gender affirming services, including provision of feminising hormones. Transgender women should be included in PrEP recommendations, with guidance about how to adapt services to meet their needs.

We report an unplanned subgroup analysis of transgender women in the iPrEx randomised controlled trial and open-label extension with respect to PrEP efficacy, effectiveness, PrEP drug concentrations, and patterns of adherence.

Section snippets

Study design and participants

The iPrEx trial was a randomised, double-blind, placebo-controlled, phase 3 clinical trial of once daily oral emtricitabine and tenofovir disoproxil fumarate PrEP for HIV prevention done between 2007 and 2011 in Brazil, Ecuador, Peru, South Africa, Thailand, and the USA.16 The randomised controlled trial was followed by an open-label extension between 2011 and 2013.17

Inclusion and exclusion criteria for iPrEx have been reported previously.16 People assigned male sex at birth were eligible for

Results

In the iPrEx trial, among 2499 enrolled participants across all 11 sites, 296 (12%) participants identified as transgender and 29 (1%) participants identified as a woman. An additional 14 (1%) male-identified participants reported exogenous female hormone use of some kind. The total number of participants from each of these three categories aggregated into the transgender women group was 339 (14%). The distribution of transgender women participants as well as sub-identities within this group

Discussion

PrEP use in transgender populations is protective in the setting of drug adherence; none of the transgender women who became infected in the randomised controlled trial had detectable drug at the time of seroconversion in the randomised phase. Furthermore, quantitative analysis of long-term drug exposure, afforded by use of dried blood spots in the iPrEx open-label extension, revealed that seroconversion occurred only among transgender women having drug concentrations commensurate with using

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