Trial ‘definitively’ shows superiority of long-acting injectable PrEP
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A PrEP regimen containing long-acting injectable cabotegravir provided superior protection against HIV infection compared with daily oral PrEP, updated study findings confirmed.
Data from the HIV Prevention Trials Network 083 study (HPTN 083) showed that participants who received injectable cabotegravir (ViiV Healthcare) every 8 weeks as part of the regimen were 66% less likely to acquire HIV than those taking daily oral emtricitabine/tenofovir disoproxil fumarate (FTC/TDF).
HPTN 083 is a phase 2b/3 randomized multicenter double-blind, double-dummy clinical trial that enrolled more than 4,500 transgender women and cisgender men who have sex with men (MSM) at 43 sites in Africa, Asia, Latin America and the United States. The blinded portion of the study was terminated after a data safety and monitoring board (DSMB) found that the study data indicated cabotegravir was highly effective at preventing HIV, the NIH and ViiV announced in May, along with releasing an interim analysis of the data.
Raphael J. Landovitz, MD, MSc, professor of medicine at the University of California, Los Angeles Center for Clinical AIDS Research and Education, presented the updated data during the AIDS 2020 virtual meeting.
Landovitz said the findings “definitively” established the superiority of cabotegravir over FTC/TDF for HIV PrEP, but that both regimens were safe and highly effective as HIV prevention tools.
“Despite remarkable efficacy of daily oral FTC/TDF to prevent HIV infections in diverse transmission contexts and populations, its public health impact has not delivered uniform benefits to all populations,” Landovitz said during his presentation. “Those disproportionately affected by HIV are the same populations that have not found equal access, uptake adherence and persistence to oral tablet-based pre-exposure prophylaxis.”
‘Incredibly important data’
Landovitz and colleagues randomly assigned study participants in a 1:1 ratio to receive either cabotegravir plus FTC/TDF placebo — oral cabotegravir for 5 weeks, then intramuscular (IM) injections every 8 weeks for 148 weeks — or active FTC/TDF plus cabotegravir placebo.
They documented 52 incident HIV infections during the study period, including 39 in the FTC/TDF arm and 13 in the cabotegravir arm, for incidence rates of 1.22% (95% CI, 0.87-1.67) and 0.41% (95% CI, 0.22-0.69), respectively, and an HR of 0.34 (95% CI, 0.18-0.62) favoring cabotegravir.
Adherence to FTC/TDF was high, Landovitz and colleagues reported, and both regimens were well tolerated. Injection site reactions caused 47 participants to discontinue injections in the active cabotegravir arm.
“This is incredibly important data, which is why we chose it for our co-chairs session,” said Monica Gandhi, MD, MPH, professor of medicine at the University of California, San Francisco, and the San Francisco co-chair of the conference, who was not involved in the study.
“However, we do need to confirm that the HIV breakthroughs on cabotegravir did not occur with integrase inhibitor resistance, as that would curtail the ability to use first-line dolutegravir-based therapy for their treatment.,” Gandhi told Healio. “That data is forthcoming.”
Landovitz said drug concentration and resistance data are forthcoming and will help explain “the clinical implications of all of these provocative findings and exciting results” and the advantages of each regimen.
“It's tremendously exciting to have data that will hopefully support regulatory approvals of an additional PrEP agent to increase choices for HIV prevention,” Landovitz said.
Companion studies
A companion trial, HPTN 084, is currently evaluating injectable cabotegravir as HIV PrEP among cisgender women who are at an increased risk for HIV in seven African countries. ViiV said in May that the DSMB also reviewed data from that trial and recommended that it continue as planned.
“It’s critical that we have a full data set that includes cisgender and transgender women as well as MSM,” Kimberly Smith, MD, MPH, head of research and development for ViiV, told Healio.
“We are also looking to gain experience with cabotegravir for prevention in other populations and geographic regions,” Smith said “Adolescents are also a very important risk group and we’ve started enrollment in two studies very similar to 083 and 084 in adolescents and we would love to demonstrate efficacy of cabotegravir in those populations as well.”
Cabotegravir is already part of a long-acting injectable HIV treatment regimen that has been approved in Canada and is under review by the FDA.
Perspective
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Paul A. Volberding, MD
This is certainly one of the most anticipated reports at AIDS 2020, showing the potential for PrEP using the new long-acting injectable integrase inhibitor cabotegravir. In the HPTN 083 trial supported by the National Institute of Allergy and Infectious Diseases, HIV-uninfected MSM and transgender women were treated with IM cabotegravir injections every 8 weeks compared with a randomized group who received to current standard PrEP approach using the fixed-dose combination of TDF and FTC. Almost 5,000 people participated in the study and the results show that both treatments were effective with low rates of new HIV infections, but participants in the long-acting injectable arm were significantly less likely to get infected with a very low rate of treatment discontinuation (only 2.2%) in that group. These results were anticipated by preliminary announcements in May, but these data based on full analysis confirmed that these PrEP injections were effective and well tolerated. The data add to our understanding of this important new option in HIV prevention, which promises to be a popular new direction in this crucially important field.
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Landovitz R, et al. HPTN 083 interim results: Pre-exposure prophylaxis containing long-acting injectable cabotegravir is safe and highly effective for cisgender men and transgender women who have sex with men. Presented at: International AIDS Conference; July 6-10, 2020 (virtual meeting).
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