An international trial of an injectable drug designed to prevent HIV was halted Monday after an early look at data showed significantly fewer new HIV infections among those given the shots compared to participants assigned a once-a-day pill.
“This is a real win for HIV prevention,” said Dr. Deborah Donnell of the Vaccine and Infectious Disease Division of Fred Hutchinson Cancer Research Center in Seattle.
Donnell helped to design and manage data from the study, known as HPTN 083, which was launched in December 2016 by the HIV Prevention Trials Network, based in Durham, North Carolina.
The study was intended to run until November 2022 to test whether injections every other month of the drug, cabotegravir [cabo-teg-gra-veer], might be just as effective as Truvada, an HIV-prevention pill proven to reduce HIV infections by 90%. But a planned early look at the data showed that the participants given the shots were one-third less likely to become infected than those who were assigned to the pills.
“To have something that is long-acting and this successful in preventing HIV acquisition is really a breakthrough for people at risk,” Donnell said.
The study enrolled 4,500 participants in the United States, Latin America, Asia and Africa. The group comprised men who have sex with men and transgender women who have sex with men. The hope was to find a prevention alternative for people at risk for HIV who have difficulty adhering to the one-pill-a-day requirement for Truvada.
Early analyses of experimental drugs by an independent Data and Safety Monitoring Board are routine in drug trials, but they seldom alter the course of the trials. But this scheduled DSMB review discovered 38 infections, or 1.21%, among those assigned to Truvada; but there were only 12 infections, or 0.38%, in those who received the injections.
The designers of the “non-inferiority” trial were looking for evidence that the group receiving the injectable drug might have similar, or at best, 25% fewer infections. Instead the early review showed there were more than three times as many infections among those assigned to take the pills.
“Until we have a safe and effective vaccine for HIV, we must continue to find innovative prevention strategies,” said Dr. Myron Cohen, HPTN co-principal investigator and director of the Institute for Global Health & Infectious Diseases at the University of North Carolina at Chapel Hill, in a press release. “Increasing the number of effective tools will give people who want to prevent HIV an opportunity to find a method that works for them.”
Cabotegravir is an antiviral drug that blocks integrase, a blood cell enzyme that HIV uses to help commandeer and eventually destroy a person’s immune cells. Developed by ViiV Healthcare Ltd., a North Carolina company founded by pharmaceutical giant GlaxoSmithKline, it has been approved as an HIV treatment only in Canada thus far, but is being tested for its potential to prevent HIV in this trial and others.
Truvada has been a transformative drug for HIV prevention. A reformulation of two antiviral medications used to treat HIV, tenofovir and emtricitibane, it was approved in 2012 as a once-a-day pill for people who are not infected but are at high risk of contracting HIV.
Use of antiviral drugs, known as pre-exposure prophylaxis, or PrEP, is a cornerstone of the Trump administration’s proposal to eliminate new HIV cases in the United States by 2030. The proposed program relies on assuring that all those who test positive for HIV receive antiviral treatment, which virtually eliminates the ability to transmit the virus. It calls for an ambitious program of outreach to provide testing to those who are impoverished or lack regular access to medical care, and it relies on PrEP to reduce infection rates in those at highest risk.
While Truvada has proven to be remarkably effective in reducing HIV infection, it will not work for those who forget, neglect or are unable to take the pills every day. Hence, the desire to find alternatives, such as an injection that only has to be given every two months.
HTPN 083 was an extraordinarily complex undertaking. The 4,500 HIV-negative enrollees were assigned to one of two arms in the trial. Each received the bimonthly injections and a daily supply of pills. But one group received cabotegravir and dummy pills instead of Truvada; the other group received an injection of saline solution and Truvada. Neither the participants nor their clinicians knew who was assigned to which arm of the trial. But the “double-dummy, double-blind” design allowed the researchers to compare the results of those taking cabotegravir to those receiving the pills. None of the participants went without one form of PrEP or the other.
Now that the trial has ended, those who were receiving cabotegravir will continue to receive it; those who received Truvada have a choice of remaining on Truvada or receiving cabotegravir when supplies are available.
A second trial, called HPTN 084, is comparing the efficacy of cabotegravir to Truvada for women in sub-Saharan Africa. Because that study began a year after the 083 study, there is insufficient data to conclude whether the injectable drug offers similar advantages, so that trial will continue without interruption.
HPTN is funded by the National Institutes of Health. The HPTN 083 study was funded by the National Institute of Allergy and Infectious Diseases and ViiV Healthcare, the maker of cabotegravir; products for the study were provided by ViiV and Gilead Sciences Inc., maker of Truvada.
Sabin Russell is a former staff writer at Fred Hutchinson Cancer Center. For two decades he covered medical science, global health and health care economics for the San Francisco Chronicle, and he wrote extensively about infectious diseases, including HIV/AIDS. He was a Knight Science Journalism Fellow at MIT and a freelance writer for the New York Times and Health Affairs.
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