Cabotegravir safe and effective for PrEP in transgender women, global study finds

While injectable cabotegravir (CAB) is effective at preventing seroconversions among transgender women, the drug’s price and diagnostic requirements mean tenofovir disoproxil fumarate (TDF)-based pre-exposure prophylaxis (PrEP) is still needed, according to a recently published study.

About This Study

“Efficacy, safety, tolerability, and pharmacokinetics of long-acting injectable cabotegravir for HIV pre-exposure prophylaxis in transgender women: a secondary analysis of the HPTN 083 trial” was published online on Sept. 29, 202, in The Lancet HIV. The lead author is Mark A. Marzinke, Ph.D., of Johns Hopkins University in Baltimore, Maryland. The study was partly funded by ViiV Healthcare, the manufacturer of the study drug.

An associated commentary, “Optimising oral PrEP while awaiting long-acting cabotegravir,” was co-written by Sheena McCormack, M.D., of the MRC Clinical Trials Unit at University College London and of the Institute of Clinical trials and Methodology in London, United Kingdom, and Mackenzie Leigh Cottrell, Pharm.D., of the Division of Pharmacotherapy and Experimental Therapeutics at the UNC Eshelman School of Pharmacy in Chapel Hill, North Carolina.

Key Research Findings

HPTN 083 is an ongoing, phase 2b/3, randomized, multicenter, double-blind, clinical trial carried out at 43 sites in seven countries (Argentina, Brazil, Peru, United States, South Africa, Thailand, and Vietnam). This secondary analysis included data on the 570 transgender women enrolled in the HPTN 083 trial, comparing two PrEP agents: CAB (266 women) and TDF (304 women). Most participants were from Asia (39% of participants) and Latin America (36% of participants), and the median age was 23 years.

A range of genders was observed in the study, including participants who self-identified as cisgender men who have sex with men, but included those who were also taking gender-affirming hormones. Overall, 58% of participants reported hormone use. CAB concentrations did not differ by such use.

Experiences of sexual abuse and intimate partner violence, depressive symptoms, lack of HIV risk awareness, and sexually transmitted infections were common. There were nine HIV acquisitions–7 in the TDF arm and 2 in the CAB arm. Participants who seroconverted on TDF had low drug concentrations. The two seroconversions on CAB occurred during oral lead-in and over two years after the last injection, respectively.

Discussion Highlights and Implications for Practice

Reported study limitations included a sample size that did not allow a full statistical comparison, gender identity that was only captured once at enrollment, and no assessment of hormone concentrations or any formal analysis of interaction between drugs and hormones.

The researchers emphasized that these findings suggest that injectable cabotegravir is a safe and effective HIV prevention strategy for transgender women.

The authors of the related commentary noted that while injectable CAB is safe and effective, it is costly and the necessary HIV diagnostics may not be available everywhere. Prescribers should be aware of updated World Health Organization guidelines for oral PrEP, including recommendations for transgender women not taking hormones. Diverse gender identities and sociobehavioral factors also need to be considered in CAB implementation studies.

By Barbara Jungwirth