New therapy may effectively control HIV in Uganda

(Press-News.org) A multi-national, multi-institutional study led by Weill Cornell Medicine investigators found little natural resistance to a new HIV therapy called lenacapavir in a population of patients in Uganda.

The study, published Jan. 30 in the Journal of Antimicrobial Chemotherapy, adds to growing evidence that lenacapavir may be a powerful new tool in the global anti-HIV drug arsenal. Approximately, 1.5 million people are living with HIV in Uganda.

“Our data shows that only 1.6% of the individuals studied are living with HIV strains that have any known lenacapavir-associated resistance mutations,” said senior author Dr. Guinevere Lee, assistant professor of virology in medicine at Weill Cornell Medicine. “That’s important because it shows lenacapavir is likely to be effective against strains of HIV circulating in East Africa.”

Since the 1990s, HIV drug combinations targeting different steps in the virus’ life cycle have been able to reduce virus load in patients to nearly undetectable levels. But drug resistance is a growing concern as the virus has evolved ways to thwart existing therapies. Lenacapavir, however, is the first drug to disrupt the protective capsid layer surrounding HIV’s genetic material (RNA), blocking the virus’s ability to reproduce and be transmitted from person to person.

Treatment twice a year with lenacapavir has been effective in patients who have never been treated and those with HIV strains that are resistant to other drugs. Last year, clinical trials showed that lenacapavir injections were 100% effective in preventing HIV infection among women in sub-Saharan Africa, who were HIV-negative.

However, little information was available about pre-existing resistance to lenacapavir in less well-studied HIV-1 strains like subtype A1 and D, which are more common in Eastern and Southern Africa. HIV-1 subtype B strains, which predominantly affect Europe and the United States, rarely have pre-existing mutations that would cause lenacapavir drug resistance. 

Dr. Lee and her colleagues at Mbarara University of Science and Technology in Uganda and Massachusetts General Hospital in Boston helped fill that gap. They sequenced the capsid proteins from HIV-1 subtypes A1 and D from 546 Ugandan patients, who had never used antiretroviral therapy before. This approach allowed the investigators to examine naturally circulating viral variants.

They found that none of the patients had genetic mutations that would lead to major lenacapavir resistance. Only nine participants had minor lenacapavir resistance mutations that could partially reduce the effectiveness, but not enough to cause full resistance to the drug.

“Our study supports lenacapavir’s potential efficacy in this region. As lenacapavir is rolled out in East Africa, further studies will need to monitor for the emergence of drug-resistant strains,” Dr. Lee said. “It is important that we ensure HIV research reaches understudied communities where unique viral strains circulate.”

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