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

Abstract

Summary Background Oral emtricitabine-tenofovir disoproxil fumarate (FTC/TDF) pre-exposure prophylaxis (PrEP) is used to prevent the sexual acquisition of HIV. Transgender women (TGW) have unique characteristics that may relate to PrEP use, effectiveness, and safety. Methods The iPrEx trial was a randomized controlled trial (RCT) of oral FTC/TDF PrEP versus placebo among men who have sex with men (MSM) and TGW, followed by an open label extension (OLE). Drug concentrations were measured in blood by liquid chromatography and tandem mass spectroscopy. Findings Of the 2499 participants enrolled in the RCT, 29 (1%) identified as women, 296 (12%) identified as “trans”, 14 (1%) identified as men but reported use of feminizing hormones, such that 339 (14%) reported one or more of these characteristics (TGW). Compared with MSM, TGW more frequently reported transactional sex, receptive anal intercourse without a condom, or more than 5 partners in the past 3 months. Among TGW, there were 11 HIV infections in the active arm and 10 in the placebo arm, representing a hazard ratio of 1.1 (95% CI: 0.5 to 2.7). Among active arm participants, drug was detected in none of the TGW at the seroconversion visit, 18% (6/37) of seronegative TGW (P=0.31), and 52% (58/111) of seronegative MSM (P < 0.0001). PrEP use was not linked to behavioral indicators of HIV risk among TGW, while MSM at highest risk were more adherent. Interpretation There were no HIV infections among TGW having drug concentrations commensurate with use of 4 or more FTC/TDF tablets per week. TGW receiving PrEP had low drug concentrations, especially at times of potential HIV exposure, leading to no PrEP effectiveness among this subgroup. Funding U.S. National Institutes of Health and the Bill and Melinda Gates Foundation; study medication was donated by Gilead Sciences.

HIV Prevention Among Transgender Populations: Knowledge Gaps and Evidence for Action

“…The seminal study of PrEP, the iPrEx trial, was designed to assess PrEP efficacy among men who have sex with men but did not exclude transgender women [48]. A sub-analysis of data on transgender women (n = 339) in this trial (Table 1) demonstrated no PrEP efficacy among transgender women, in an intent-to-treat analysis [49]. Adherence among transgender women was remarkably low at 18%.…”

“…Of note, iPrEx participants who were taking hormone therapy had lower levels of TDF detected than those who did not, suggesting that transgender women either prioritized hormone therapy over PrEP or that a drug-drug interaction may exist [49]. While there is no evidence of drug-drug interactions between TDF and estrogen-containing oral contraceptives medications [50], there are tissue specific in vitro differences in TDF pharmacokinetics in the presence of estrogen [51–53].…”

Barriers and Facilitators to Oral PrEP Use Among Transgender Women in New York City

“…Though this method of HIV prevention, called oral PrEP here, is highly efficacious, its initiation and consistent use remains low in some population segments, such as transgender women (e.g., individuals who were assigned male at birth but identify as women)(2–4). This is concerning, since PrEP has the potential to mitigate the high prevalence of transgender women living with HIV in the U.S. (~22%) (5).…”

HIV and trans and non-binary people in the UK

“…Some of the landmark PrEP trials have included trans women as participants, although many have either misclassified trans women’s gender identities or have not disaggregated data from trans women from those from men who have sex with men. A post-hoc subgroup analysis of data on 339 trans women in the iPrEx trial revealed a high number of HIV seroconversions in the intervention group, all linked to poor adherence 10. In this analysis, trans women who reported use of feminising hormones were less likely to have detectable drug levels 10.…”

“…A post-hoc subgroup analysis of data on 339 trans women in the iPrEx trial revealed a high number of HIV seroconversions in the intervention group, all linked to poor adherence 10. In this analysis, trans women who reported use of feminising hormones were less likely to have detectable drug levels 10. One of the only studies to date in the UK, a survey of 44 trans people testing for HIV at a sex-on-premises venue in London, found that over two-thirds reported no knowledge of PrEP or post-exposure prophylaxis, with many expressing concerns about cost, reliability and potential drug interactions with hormone therapy 11…”