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Study on Lenacapavir Shows Promising Results in Uganda

A recent international study led by investigators from Weill Cornell Medicine has revealed promising findings regarding a novel HIV treatment called lenacapavir. This research, conducted in Uganda, demonstrates minimal natural resistance to this therapy among the local patient population.

Published on January 30 in the Journal of Antimicrobial Chemotherapy, the study contributes to a growing body of evidence supporting lenacapavir as an important addition to global HIV treatment options. In Uganda, approximately 1.5 million individuals are currently living with HIV.

Dr. Guinevere Lee, the senior author and an assistant professor of virology in medicine at Weill Cornell Medicine, stated, “Our findings indicate that only 1.6% of the individuals we studied carry HIV strains with known lenacapavir-associated resistance mutations. This observation is crucial because it suggests that lenacapavir is likely to be effective against the strains of HIV circulating in East Africa.”

Since the emergence of HIV treatments in the 1990s, combination therapies that target various stages of the virus’s lifecycle have successfully reduced viral loads in patients to levels that are nearly undetectable. Nevertheless, the issue of drug resistance remains significant, as HIV evolves mechanisms to resist existing treatments. Lenacapavir stands out as the first drug designed to target the virus’s protective capsid layer, which encases its genetic material (RNA). This innovative approach hinders the virus’s ability to reproduce and spread.

The treatment regimen of lenacapavir, administered biannually, has shown effectiveness in both treatment-naive patients and those with HIV strains resistant to other antiretroviral therapies. Notably, clinical trials conducted last year reported that lenacapavir injections achieved a 100% success rate in preventing HIV infection among HIV-negative women in sub-Saharan Africa.

Despite these advances, there has been limited information on the presence of pre-existing resistance to lenacapavir in lesser-studied HIV-1 strains, particularly subtypes A1 and D, which are prevalent in Eastern and Southern Africa. In contrast, the HIV-1 subtype B strains, which are more common in Europe and the United States, rarely exhibit pre-existing mutations associated with lenacapavir resistance.

To address this knowledge gap, Dr. Lee and her team, in collaboration with researchers from Mbarara University of Science and Technology in Uganda and Massachusetts General Hospital in Boston, sequenced the capsid proteins from HIV-1 subtypes A1 and D in samples from 546 Ugandan patients who had not undergone prior antiretroviral therapy. This method facilitated the examination of naturally occurring viral variants.

The results revealed that none of the participants exhibited significant genetic mutations that would confer major resistance to lenacapavir. Although nine participants possessed minor mutations that could slightly diminish drug efficacy, these variations were not substantial enough to result in complete resistance.

“Our findings bolster the potential efficacy of lenacapavir in this region,” Dr. Lee noted. “As we begin to implement lenacapavir in East Africa, it will be essential to continue researching to monitor for the emergence of any drug-resistant strains. Ensuring that HIV research reaches communities that are often overlooked is critical, especially where unique viral strains may be circulating.”

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