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Publicação
Susceptibility to Lenacapavir Among Newly Diagnosed HIV-Positive Patients Followed Up in Mozambique That Presented With Primary Antiretroviral Resistance to Other Classes
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Orientador(es)
Resumo(s)
Multidrug-resistant HIV patients have limited ART options. Lenacapavir (LEN) is a capsid inhibitor that exhibits substantial antiviral activity in patients with therapeutic failure but is also proposed for PrEP. Herein, we assessed LEN susceptibility among ART-naive HIV patients with drug resistance in Mozambique. In this study, 63 patients with DRM against PIs, NRTIs, NNRTIs, and INSTIs were included. The gag (p24) and env fragments were amplified with a low-cost in-house protocol and sequenced with nanopore. HIVDR database from Stanford University was used to assess LEN resistance and geno2pheno to assess viral tropism and protease/maturation inhibitor-associated mutations. A total of 59 patients were successfully sequenced. About 29% had DRMs to PIs, 5% to NRTI, 83% to NNRTI, and 2% to INSTI. No DRMs to LEN were detected. Additionally, 42% of the sequences presented protease/maturation inhibitor-associated mutations. A relationship was observed between the E138A/G mutation and protease/maturation inhibitors (p = 0.004). We identified changes at the first codon position of position 56 of the p24 gag gene, which represents a key site for resistance to LEN. Also, codon 66 was highly conserved. Our results support the potential effectiveness of lenacapavir as a PrEP regimen or rescue therapy for patients with at least one drug-resistance mutation.
Descrição
Funding Information: The authors thank all participants in this study. Furthermore, thanks to CISM for the logistical support that allowed patient recruitment and management. This study was funded by FCT-Foundation for Science and Technology (MARVEL project - PTDC/SAU-PUB/4018/2021), GHTM-UID/04413/2020, and LA-REAL-LA/P/0117/2020. The funders have no role in the conceptualization, design, data collection, analysis, decision to publish, or preparation of the manuscript. Publisher Copyright: © 2025 The Author(s). Journal of Medical Virology published by Wiley Periodicals LLC.
Palavras-chave
drug resistance mutations HIV-1 lenacapavir Mozambique Infectious Diseases Virology SDG 3 - Good Health and Well-being