Kate Johnson
MONTREAL — Long-acting injectable cabotegravir (CAB LA) continues to show superiority over daily oral tenofovir diphosphate plus emtricitabine (TDF-FTC) as pre-exposure prophylaxis (PrEP) for HIV, according to new data from two HIV Prevention Trial Networks (HPTN) studies reported here at the 2022 International AIDS Society (IAS) Conference.
Follow-up data from the HPTN 084 trial, which compared the two regimens in 3,224 sub-Saharan Africans assigned female at birth, show that three new HIV infections occurred in the CAB LA group in the 12 months since the study began, versus 20 new infections in the TDF-FTC group. This translates to an 89% lower risk of infection in the CAB LA arm in both the blinded and unblinded phases of the trial, said lead investigator Sinead Delany-Moretlwe, MD, PhD, director of research at the Wits Reproductive Health and HIV Institute, University of the Witwatersrand, Johannesburg, South Africa, during a press conference.
“The trial was designed under the assumption that both drugs were highly effective at preventing HIV infection , but given the challenges of taking a pill every day, injectable cabotegravir might offer an advantage in adherence,” he told Medscape Medical News . “Our data appear to confirm this, as most of the participants in the TDF-FTC arm who became infected with HIV had evidence of poor or inconsistent PrEP use.”
The study also found that the incidence of pregnancies increased two to three times between the blinded and unblinded periods, "and this underscores women's desire to conceive safely, without the threat of HIV, and the importance of continuing to evaluate the safety and pharmacology of cabotegravir in pregnant and breastfeeding women during the open-label extension phase of HPTN 084, so that they are not excluded from access to this highly effective PrEP agent," she said. To date, no birth defects have been reported in infants born during the study.
In an update report of HPTN 083, which also showed the superiority of CAB LA over TDF-FTC in cisgender men and transgender women (TGW), researchers reported the safety and efficacy of using CAB LA in TGW using gender-affirming hormone therapy (GAHT).
Among the 4566 participants in HPTN 083, 570 were TGW, and of those, 58% used GAHT at the start of the study, reported Beatriz Grinsztejn, MD, PhD, head of the STD/AIDS Clinical Research Laboratory of the National Institute of Infectology/Oswaldo Cruz Foundation.
The concentrations of the drug CAB LA measured in a subset of 53 transgender women who received timely CAB injections were comparable between those taking (n = 30) and those not taking GAHT (n = 23), “suggesting a lack of gender-affirming hormone effect on the pharmacokinetics of CAB,” she said. “These are very promising results, as we all know that the use of gender-affirming hormone therapy is a major priority for our transgender women community, so the lack of drug interaction is a really important result.”
"Cabotegravir long-acting PrEP is now approved for all at-risk populations, including men who have sex with men, transgender women, and cisgender women, following the results of HPTN 083 and 084," commented Monica Gandhi, MD, MPH, an infectious disease physician, professor of medicine, and associate chief of the Division of HIV, Infectious Diseases and Global Medicine at the University of California, San Francisco (UCSF).
Gandhi, who was not involved in either study, is also director of the UCSF AIDS Research Center and medical director of the HIV Clinic (“Ward 86”) at San Francisco General Hospital. “The incredible efficacy of long-acting PrEP for cisgender women shown by HPTN 084 is a game-changer for our practice, and we have already instituted CAB LA in a variety of populations at Ward 86,” he told Medscape. “The 89% durability of additional efficacy of CAB LA over oral TDF/FTC is exciting and will lead to greater use of long-acting options.”
He acknowledged that information was needed on the potential interactions of GAHT from the HPTN 083 trial. "The fact that cabotegravir levels did not change with the use of spironolactone for gender-affirming therapy is important news for our practice and to assure our TGWs that they can safely and effectively use CAB LA for HIV prevention."