LONDON—ViiV Healthcare has announced that an independent data safety monitoring board (DSMB) recommended the early unblinding of the HIV Prevention Trials Network (HPTN) 084 study evaluating the safety and efficacy of investigational, long-acting, injectable cabotegravir for HIV prevention in women. Following a pre-specified interim analysis, the DSMB indicated that cabotegravir met the primary objective of demonstrating superiority when compared to the current standard of care for women: daily oral emtricitabine/tenofovir disoproxil fumarate 200 mg and 300 mg (FTC/TDF) tablets. Cabotegravir was found to be 89 percent more effective than daily oral FTC/TDF for pre-exposure prophylaxis (PrEP).
Cabotegravir is an investigational integrase inhibitor being developed for the treatment and prevention of HIV. ViiV Healthcare is assessing the compound as both a long-acting formulation for intramuscular injection and a once-daily oral tablet for use as a lead-in, to establish the tolerability of cabotegravir prior to long-acting injection.
The HPTN 084 study—which features 3,223 participants in 20 sites across seven countries in sub-Saharan Africa (Botswana, Kenya, Malawi, South Africa, eSwatini, Uganda and Zimbabwe)—is the first study of long-acting injectable therapy for HIV prevention among women. The data showed that there was a statistically significant advantage for the women who received cabotegravir compared with the women who received FTC/TDF.
“It’s thrilling to collaborate with the NIH and the Bill & Melinda Gates Foundation to conduct such an important study in HIV prevention in women and deliver groundbreaking results confirming the superior efficacy of long-acting cabotegravir for PrEP,” Dr. Kimberly Smith, head of Research & Development at ViiV Healthcare, said in a press release. “Women need more effective choices for HIV prevention. If approved, long-acting cabotegravir will provide an option that reduces the number of annual dosing days from 365 to six. In addition, long-acting cabotegravir can be discretely administered and may empower women to reduce their risk of HIV acquisition without the need for negotiation with their sexual partner. The results of HPTN 084 confirm long-acting cabotegravir’s potential as an HIV prevention option that can meet these needs.”
Of the 38 women in the trial who acquired HIV, four were randomized to the long-acting cabotegravir arm and 34 were randomized to the FTC/TDF arm. This translated to an HIV incidence rate of 0.21 percent in the cabotegravir group and 1.79 percent in the FTC/TDF group. While both methods were highly effective at preventing HIV acquisition, long-acting cabotegravir was 89 percent more effective than FTC/TDF.
Long-acting cabotegravir and FTC/TDF tablets were both well tolerated by study participants, with most adverse events being mild or moderate in severity and with the frequency largely balanced between both treatment arms. Injection site reactions (ISRs) were low in both groups and represented numerical improvements from what was demonstrated in the HPTN 083 study in men. ISRs in HPTN 084 occurred more frequently in the cabotegravir arm (32 percent) vs. the FTC/TDF arm (9 percent), which received placebo injections. There were no discontinuations due to injection site reactions or injection intolerance in either arm of the study. Gastrointestinal disorders and nausea were more common in the FTC/TDF arm.
Following review of the data, the DSMB recommended that the blinded, randomized portion of the study be stopped early, all participants unblinded and results released. Participants in the FTC/TDF arm will be offered long-acting cabotegravir and participants in the long-acting cabotegravir arm will continue to receive it. Participants who do not want to receive long-acting cabotegravir will be offered FTC/TDF until the end of the originally planned blinded component of the study. The DSMB recommendation was accepted by the study's sponsor, the U.S. National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH).
“With the combined landmark findings of HPTN 084 announced today and HPTN 083 announced earlier this year, we’ve confirmed that long-acting cabotegravir is a superior HIV prevention option for men and women. New HIV prevention agents that address the many needs of all individuals at risk for acquiring HIV are essential pillars of our strategy to end the HIV epidemic. If approved, this innovative new injectable option administered once every two months will expand the way we approach HIV prevention,” commented Dr. Myron S. Cohen, co-principal investigator of the HPTN and the Yeargan-Bate Distinguished Professor of Medicine, Microbiology and Immunology and Epidemiology at the University of North Carolina at Chapel Hill.
HPTN 084 was jointly funded by the U.S. NIAID and the National Institute of Mental Health, both part of the NIH, the Bill & Melinda Gates Foundation, and ViiV Healthcare. The study was conducted by the HPTN.