Findings reported earlier this year from a companion study established that the long-acting injectable regimen was safe and more effective than a daily oral PrEP regimen at preventing HIV among cisgender men and transgender women who have sex with men. Both studies are sponsored by NIH’s National Institute of Allergy and Infectious Diseases (NIAID) and conducted by the NIH-funded HIV Prevention Trials Network (HPTN). NIAID is co-funding the trial in cisgender women in a unique partnership with ViiV Healthcare and the Bill & Melinda Gates Foundation. ViiV Healthcare and Gilead Sciences, Inc. are providing study medications.
Currently, only one PrEP medication, a daily oral pill that contains the HIV drugs emtricitabine and tenofovir disoproxil fumarate (brand name Truvada), is approved by the U.S. Food and Drug Administration for individuals at risk of acquiring HIV from receptive vaginal sex. While Truvada is highly effective at preventing sexual acquisition of HIV when taken daily as prescribed, a safe and effective long-acting injectable form of PrEP would offer a new option for HIV prevention that may be easier and more desirable for some women.
Launched in late 2017, the Phase 3 trial, called HPTN 084, enrolled 3,223 HIV-negative, sexually active cisgender women at 20 clinical research sites in Botswana, Eswatini, Kenya, Malawi, South Africa, Uganda and Zimbabwe. They range in age from 18 to 45 years, with an average age of 26 years. Participants were randomly assigned to receive either injections of cabotegravir every eight weeks and placebo daily oral tablets or placebo injections every eight weeks and daily oral Truvada. Neither the participants nor the study team knew who was receiving which medication.
In a planned interim review meeting on Nov. 5, 2020, the independent data and safety monitoring board (DSMB) for HPTN 084 found that the study data indicated that long-acting injectable cabotegravir had superior efficacy to Truvada at preventing HIV in the study population. Among the 38 women in the trial who acquired HIV, four were receiving long-acting cabotegravir and 34 were receiving daily oral Truvada. This translated to an HIV incidence rate of 0.21% (95% confidence interval [CI] 0.06%-0.54%) in the cabotegravir group and 1.79% (95% CI 1.24%-2.51%) in the Truvada group. While both PrEP methods were highly effective at preventing HIV acquisition, the protective effect of cabotegravir met the statistical criteria for superiority (hazard ratio, 0.11; 95% CI 0.04-0.32).
Both cabotegravir and Truvada were well-tolerated among women in the study, and the DSMB found no safety concerns. Some participants experienced pain or tenderness at the injection site; this was more common among women in the cabotegravir group compared to those in the Truvada group, who received placebo injections. Most women in the cabotegravir group received their injections as scheduled, and no participants discontinued injections due to side effects. Adherence to daily oral PrEP can be challenging for some people; 64% of a subset of 362 HPTN 084 participants who provided blood samples had detectable concentrations of tenofovir in their blood. Investigators are continuing to analyze and gather data to determine the role that adherence plays.
Based on their review, the DSMB recommended that NIAID stop the blinded phase of the trial, originally designed to continue until 2022, and share the results. NIAID agreed with the DSMB’s recommendations and is releasing the results now in the interest of public health. The HPTN 084 investigators will report more detailed information about the study findings, including more comprehensive data, as soon as feasible.
HPTN 084 participants will be informed of the findings and told which medication they were receiving. They will be offered the opportunity to continue in the trial, initially remaining on the PrEP medication that they were assigned to at the beginning of the study. Participants taking Truvada who wish to switch to long-acting cabotegravir will be able to do so as soon as it can be made available. Investigators will continue following participants to gather data about the long-term safety of injectable cabotegravir for HIV prevention among cisgender women.
More information about HPTN 084 and the companion study in men and transgender women who have sex with men, called HPTN 083, is available on ClinicalTrials.gov using identifiers NCT03164564 and NCT02720094, respectively. Three other NIH institutes also collaborate on these trials: the National Institute of Mental Health, the National Institute on Drug Abuse, and the Eunice Kennedy Shriver National Institute of Child Health and Human Development.
