ArticleThe Journal of antimicrobial chemotherapy2025
Subtypes A1 and D, and recombinant HIV-1 natural polymorphisms associated with lenacapavir drug resistance in Uganda.
Article in The Journal of antimicrobial chemotherapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Advancements in development of novel class of HIV protease inhibitors.Annals of medicine · 2026Review
- HIV drug resistance and treatment success in the Republic of Congo: Implications for optimized treatment.HIV medicine · 2026Article
- HIV-1 integrase inhibitor resistance in viraemic-treated individuals and baseline capsid diversity relevant to future lenacapavir therapy.The Journal of antimicrobial chemotherapy · 2026Article
- Lenacapavir-associated drug resistance: implications for scaling up long-acting HIV pre-exposure prophylaxis.The lancet. HIV · 2025Review
- Reply to Comment on "Prevalence of Naturally Occurring HIV-1 Capsid Inhibitor Resistance-related Mutations in Antiretroviral Therapy-naïve and -Experienced Individuals in Taiwan".Open forum infectious diseases · 2025Article
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Authors and funding
12 authors.
Funding
Abstract
backgroundLenacapavir, a novel HIV-1 capsid inhibitor, shows promise for treating MDR HIV-1, as well as for pre-exposure prophylaxis (PrEP) in prevention of HIV infection. Its unique mechanism and lack of cross-resistance with other antiretroviral classes make lenacapavir a significant addition to HIV therapy. The clinical trials CALIBRATE and CAPELLA have demonstrated high viral suppression rates in both ART-naive individuals and individuals with MDR HIV-1. Lenacapavir-associated resistance mutations, such as M66I and Q67H, rarely seen as natural polymorphisms in lenacapavir-naive populations, are predominantly studied in subtype B HIV-1.
objectivesOur study aimed to investigate the prevalence of lenacapavir resistance-associated mutations in HIV-1 subtypes A1 and D in a cohort of individuals living with HIV-1 from southwestern Uganda.
methodsUtilizing plasma samples from ART-naive adults living in Uganda, HIV-1 Gag p24 (capsid) sequences were analysed for lenacapavir resistance mutations.
resultsAmong 546 lenacapavir-naive participants, no major lenacapavir resistance-associated mutations were found. Minor mutations were present in 1.6% of participants, with T107A being the most common. Longitudinal data indicated the persistence of T107A for at least 3 years post-ART initiation in one participant. Phylogenetic analysis indicated individuals carrying T107A were found independently in distinct locations within the tree, suggesting that T107A might have arisen from multiple distinct base substitution events. Shannon entropy analysis showed high variability in certain capsid sites, but none overlapped with known lenacapavir resistance sites.
conclusionsThese findings suggest a low prevalence of naturally occurring lenacapavir resistance mutations in Uganda, supporting lenacapavir's potential efficacy in this region.
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