A new study led by Weill Cornell Medicine researchers found that a novel HIV therapy called lenacapavir shows little natural resistance in a population of patients in Uganda. This suggests lenacapavir may be a powerful tool in the fight against HIV.
A recent multi-national, multi-institutional study led by Weill Cornell Medicine researchers has revealed promising findings regarding the effectiveness of lenacapavir, a novel HIV therapy, in a population of patients in Uganda . The study, published on January 30th in the Journal of Antimicrobial Chemotherapy, suggests that lenacapavir may be a potent weapon in the global fight against HIV . Approximately 1.5 million individuals in Uganda are living with HIV .
The study's data indicates that a mere 1.6% of the participants harbored HIV strains possessing known lenacapavir-associated resistance mutations. This is a significant discovery as it demonstrates the likelihood of lenacapavir's efficacy against prevalent HIV strains circulating in East Africa.Dr. Guinevere Lee, the senior author and assistant professor of virology in medicine at Weill Cornell Medicine, emphasized the importance of these findings. She stated that since the 1990s, HIV drug combinations targeting various stages of the virus' life cycle have proven successful in reducing viral loads to nearly undetectable levels in patients. However, the ever-evolving nature of the virus has led to growing concerns regarding drug resistance. Lenacapavir, uniquely, disrupts the protective capsid layer surrounding HIV's genetic material (RNA), effectively hindering the virus's ability to replicate and transmit. Clinical trials have shown the effectiveness of lenacapavir injections, administered twice a year, in both treatment-naive patients and those with HIV strains resistant to other medications. Last year, trials showcased lenacapavir's 100% efficacy in preventing HIV infection among HIV-negative women in sub-Saharan Africa.While lenacapavir has demonstrated promising results against HIV-1 subtype B strains, which predominantly affect Europe and the United States, there was limited information regarding pre-existing resistance to lenacapavir in less studied HIV-1 strains like subtype A1 and D, which are more prevalent in Eastern and Southern Africa. Dr. Lee and her colleagues, including researchers at Mbarara University of Science and Technology in Uganda and Massachusetts General Hospital in Boston, collaborated to address this knowledge gap. They sequenced capsid proteins from HIV-1 subtypes A1 and D obtained from 546 Ugandan patients who had never received antiretroviral therapy. This approach allowed them to analyze naturally circulating viral variants. Their findings revealed that none of the patients possessed genetic mutations that would lead to significant lenacapavir resistance. Only nine participants exhibited minor lenacapavir resistance mutations that could potentially partially reduce drug effectiveness, but not to the extent of causing complete resistance. Dr. Lee emphasized the importance of continued monitoring for the emergence of drug-resistant strains as lenacapavir is implemented in East Africa. She also highlighted the need to ensure that HIV research extends to understudied communities where unique viral strains circulate, contributing to a more comprehensive understanding of the virus and its evolution
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