An independent data safety monitoring board (DSMB) indicated that cabotegravir for HIV prevention in women met the primary objective of demonstrating superiority compared with the current standard of care for women, daily oral emtricitabine/tenofovir disoproxil fumarate 200 mg and 300 mg (FTC/TDF) tablets. Further, the study showed cabotegravir was 89% more effective than daily oral FTC/TDF for pre-exposure prophylaxis (PrEP).

The early study unblinding for superior efficacy in this prevention trial in women follows results reported earlier this year from a companion study, HPTN 083, that also established long-acting cabotegravir’s superiority to daily oral PrEP in preventing HIV among men who have sex with men and transgender women who have sex with men.

The HPTN 083 study includes 3223 participants in 20 sites across 7 countries in sub-Saharan Africa and 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. Although both were highly effective at preventing HIV in the study population, cabotegravir was superior, according to the press release.

Four of the 38 women in the trial who acquired HIV were randomized to the long-acting cabotegravir arm and 34 were randomized to the daily, oral FTC/TDF arm. This translated to an HIV incidence rate of 0.21% in the cabotegravir group and 1.79% in the FTC/TDF group. Both methods were highly effective at preventing HIV acquisition, long-acting cabotegravir was 89% more effective than FTC/TDF.

A preliminary assessment of adherence to oral FTC/TDF was higher than what has been seen in prior HIV prevention studies in similar populations of women, based on a random subset of 362 FTC/TDF participants that measured any detectable tenofovir in 64% of participants with daily dosing levels of all samples tested, according to the press release.

“It’s thrilling to collaborate with the (National Institutes of Health) and the Bill & Melinda Gates Foundation to conduct such an important study in HIV prevention in women and deliver ground-breaking results confirming the superior efficacy of long-acting cabotegravir for PrEP,” said Kimberly Smith, MD, MPH, head of research and development at ViiV Healthcare, in a press release. “Women need more effective choices for HIV prevention.”

Smith added that if approved, the long-acting cabotegravir will provide an option that reduces the number of annual dosing days from 365 to 6. In addition, she noted that 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.

Long acting-cabotegravir and FTC/TDF tablets were both well tolerated throughout the study, with most adverse events being mild or moderate in severity and with the frequency largely balanced between both treatment arms. Further, injection site reactions (ISRs) were low in both groups and represented numerical improvements from what was demonstrated in the HPTN 083 study in men.

Additionally, ISRs in HPTN 084 occurred more frequently in the cabotegravir arm versus the FTC/TDF arm, which received placebo injections. There were no discontinuations due to ISRs or injection intolerance in either arm of the study, according to the press release.

“You have two major dominating pandemics in the world, HIV and COVID, and you have an extraordinary advance now with HPTN 084,” said Anthony Fauci, MD, in a press briefing. “I can say it’s a really good day for biomedical research and the clinical application of biomedical research.”

REFERENCE
ViiV Healthcare announces superiority of cabotegravir for PrEP in global HIV prevention in study in women. GCI Health [email]. Sent November 9, 2020. Accessed November 9, 2020.