A large-scale phase 2b/3 trial testing the efficacy of a novel drug designed to prevent HIV infection has been cut short due to a combination of positive early data and disruptions caused by the COVID-19 pandemic. The interim analysis of the drug suggests a single injection every eight weeks offers greater protection from HIV infection than any other medicine currently available.
“Each year, an estimated 1.7 million people are newly diagnosed with HIV,” says co-investigator on the new study Myron Cohen, from the University of North Carolina at Chapel Hill. “To lower that number, we believe more prevention options are needed in addition to currently available oral tablets for daily use.”
The trial, managed by the HIV Prevention Trials Network (HPTN), was dubbed HPTN 083. It began enrolling subjects at the end of 2016 and was designed to investigate the safety and efficacy of a new long-acting injectable drug called cabotegravir against the current standard of care for HIV prevention, a daily oral antiretroviral combination treatment of tenofovir and emtricitabine (often referred to under its brand name Truvada).
The trial enrolled around 4,600 subjects, deemed at high-risk of HIV infection, spanning seven countries around the world. The cohort was blindly split into two groups, receiving either a cabotegravir injection every eight weeks and daily placebo pills, or a placebo injection every eight weeks and daily tenofovir/emtricitabine pills.
The initial plan was to administer the treatment for three years, however, as the COVID-19 pandemic washed over the world researchers began to detect major disruptions to several trial sites. By April a quarter of the sites running the trial had reportedly shut.
In early May an independent Data and Safety Monitoring Board (DSMB) conducted an interim analysis of the data already gathered up to March 2020. The DSMB concluded the early data suggested cabotegravir was as safe as the daily tenofovir/emtricitabine treatment, and potentially much more effective. The DSMB review recommended ending the blinded part of the study, offering those in the cabotegravir placebo group the real drug, and publicly releasing these findings.
Although the data has not been peer-reviewed or published, these early results paint a promising picture of cabotegravir’s success. All up, 50 subjects acquired HIV during the course of the trial – 12 in the cabotegravir group and 38 in the tenofovir/emtricitabine group. This suggests the bi-monthly cabotegravir injections are 69 percent more effective at preventing HIV infection than current standard of care.
“Demonstrating conclusively that long-acting injectable cabotegravir is highly effective almost two years earlier than originally expected is exciting news,” says Raphael Landovitz, HPTN 083 protocol chair. “It is inspiring that we may soon have additional HIV prevention options for at-risk individuals who have difficulty with or prefer not to take pills.”
It is unclear at this stage what accounts for the still relevant levels of HIV infection seen in the trial’s cabotegravir cohort. Further analysis of the data gathered during the trial over the coming months will hopefully shine a light on the particular factors that led to the infections seen in the study.
A companion trial, labeled HPTN 084, is still ongoing. HPTN 083 focused on cisgender men and transgender women who have sex with men, whereas HPTN 084 is investigating a similar-sized cohort of women at high-risk of HIV infection in sub-Saharan Africa. The results from this second trial will help researchers understand the efficacy of cabotegravir in different populations.
“We are eagerly awaiting the results of the ongoing HPTN 084 study among African women,” says Shannon Hader, Deputy Executive Director of UNAIDS, a joint UN program aiming to eradicate HIV/AIDS by 2030. “We hope that by the end of this year there will be equally good news for women around the world.”
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