An investigational long-acting form of the HIV drug cabotegravir injected once every 8 weeks safely and effectively prevents HIV acquisition in men who have sex with men and transgender women who have sex with men. This finding, from a planned interim analysis of study data, marks the first time a large-scale clinical trial has shown a systemic, long-acting form of HIV prevention to be highly effective. The trial and an ongoing companion study evaluating long-acting injectable cabotegravir for HIV prevention in women are sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.
Daily oral pills containing the drugs tenofovir and emtricitabine, such as Truvada or Descovy, are the only currently FDA-approved form of HIV pre-exposure prophylaxis, or PrEP. Taking a daily pill while feeling healthy can be challenging for some people, so investigators have been working to develop a long-acting alternative to oral PrEP that would be at least equally effective at preventing HIV. Such a long-acting prevention method may offer an easier, discreet option that may be more desirable for some people.
NIAID collaborated on the Phase 2b/3 clinical trial in men who have sex with men and transgender women with ViiV Healthcare, Gilead Sciences, Inc., and the NIH-funded HIV Prevention Trials Network (HPTN). NIAID and ViiV Healthcare co-funded the trial, called HPTN 083, and ViiV Healthcare and Gilead Sciences, Inc., provided the study medications.
Beginning in 2016, the HPTN 083 study team enrolled 4,570 HIV-negative men who have sex with men and transgender women who have sex with men at 43 sites in Argentina, Brazil, Peru, South Africa, Thailand, the United States and Vietnam. The participants were considered at risk for HIV acquisition. Two-thirds of study participants were under 30 years of age, and 12% were transgender women. Half of the participants in the United States identified as black or African American. Participants were randomly assigned to receive either injections of cabotegravir and placebo oral tablets or placebo injections and daily oral Truvada tablets. Neither the participants nor the study team knew who was receiving which medication.
In a planned interim review of HPTN 083 on May 14, 2020, an independent data and safety monitoring board (DSMB) found that the study data clearly indicated that long-acting injectable cabotegravir was highly effective at preventing HIV in the study population. Among the 50 people in the trial who acquired HIV, 12 were receiving long-acting cabotegravir and 38 were receiving daily oral Truvada. This translated to an HIV incidence rate of 0.38% (95% confidence interval [CI] 0.20%-0.66%) in the cabotegravir group and 1.21% (95% CI 0.86%-1.66%) in the Truvada group.
Both cabotegravir and Truvada were generally safe and well-tolerated in the study population, and the DSMB found no safety concerns. Most participants in the cabotegravir group (80%) reported pain or tenderness at the injection site, compared to only 31% of those in the Truvada group, who received placebo injections.
Consequently, the DSMB recommended that NIAID stop the blinded phase of the trial, which was originally expected to continue until 2021, and share the results. NIAID has accepted the DSMB’s recommendations and is releasing the results now to serve the interests of public health. The study investigators will report more detailed information about the HPTN 083 results in the coming weeks.
The HPTN 083 study team and participants are being notified of the study results. All study participants, including those who initially received Truvada, will be offered long-acting cabotegravir as soon as it can be made available. Study investigators will continue following HPTN 083 participants to gather additional data about the long-term safety of injectable cabotegravir for HIV prevention.
The DSMB also reviewed data on May 14 from the Phase 3 companion study of long-acting cabotegravir for HIV prevention in women in southern and east Africa, called HPTN 084. That trial began a year later than HPTN 083, and the DSMB recommended that it continue as planned. To date, more than 3,000 sexually active women in seven African countries have enrolled in HPTN 084, which is co-funded by NIAID, ViiV Healthcare and the Bill & Melinda Gates Foundation.