The National Institutes of Health (NIH) is enrolling participants from 45 sites around the world to evaluate cabotegravir as long-acting injectable pre-exposure prophylaxis (PrEP).
The first phase 3 clinical trial of a long-acting injectable drug to block transmission of human immunodeficiency virus (HIV) is officially underway.
Researchers from the National Institutes of Health (NIH) have begun enrolling 4,500 men who have sex with men and transgender women who have sex with men at 45 sites around the world. Investigators will evaluate cabotegravir’s performance as a pre-exposure prophylaxis (PrEP) by randomizing patients between the experimental medication and the daily oral medication emtricitabine/tenofovir disoproxil fumarate (Truvada/Gilead Sciences)—which has proven highly effective in protecting users against HIV infection.
Patients will begin the trial by receiving two pills every day for five weeks, a placebo and either oral cabotegravir or Truvada. After that, they will either receive an injection of cabotegravir every eight weeks in a daily placebo pill or a daily Truvada pill and a placebo injection every eight weeks. After three and a half years of this treatment, all participants will be offered 48 weeks of daily oral Truvada.
Study participants will also receive HIV prevention counseling, condoms, and lubricant, along with extra counseling designed to increase adherence to the daily oral pill. Testing for sexually transmitted infections will take place throughout the study period. People who become infected with HIV will leave the study and be directed to local healthcare providers.
Investigators expect results in 2021.
“We urgently need more HIV prevention tools that fit easily into people’s lives,” Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases (NIAID), said in a news release. “Although daily oral Truvada clearly works for HIV prevention, taking a daily pill while feeling healthy can be difficult for some people. If proven effective, injectable cabotegravir has the potential to become an acceptable, discreet, and convenient alternative for HIV prevention.”
The study’s protocol chair, Raphael J. Landovitz, MD, MSc, says the need for a new form of PrEP is illustrated in the fact that the number of new HIV infections is still rising each year among high-risk individuals despite the existence of Truvada. He believes the existence of a long-lasting injectable prophylaxis would be particularly valuable, not because everyone would prefer infrequent injections to daily pills, but because the two options are different enough to work for people with significantly different preferences.
“It is essential to develop multiple effective HIV prevention modalities so the most vulnerable populations have a choice of preventive options,” Landovitz said.
The NIH, working through both the National Institute of Allergy and Infectious Diseases (NIAID) and the HIV Prevention Trials Network, is cosponsoring the new trial in conjunction with ViiV Healthcare and Gilead Sciences, Inc. A related trial, which will get underway this year, will test the safety and efficacy of injectable cabotegravir for HIV prevention in young women in sub-Saharan Africa.
Cabotegravir is not the only long-acting injectable PrEP under development. Researchers at the University of North Carolina School of Medicine and Merck have redesigned oral antiretroviral medication raltegravir as an injectable prophylaxis. Animal testing found that the drug stayed in the system at the same levels as twice-daily oral PrEP for a full two weeks.
The news release was provided by the NIH.