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Genetic Diversity in the Capsid Protein-Coding Region of HIV-1 Circulating in Benguela, Angola ; Implications for Primary Resistance to the Novel Capsid Inhibitor Lenacapavir

Title: Genetic Diversity in the Capsid Protein-Coding Region of HIV-1 Circulating in Benguela, Angola ; Implications for Primary Resistance to the Novel Capsid Inhibitor Lenacapavir
Authors: Queirós, Gonçalo; Yefimenko, Lesya; Pereira, Filomena M.; Piedade, João
Contributors: Instituto de Higiene e Medicina Tropical (IHMT); Laboratório Associado de Translacção e Inovação para a Saúde Global - LA Real (Pólo IHMT); Individual Health Care (IHC); Global Health and Tropical Medicine (GHTM); TB, HIV and opportunistic diseases and pathogens (THOP)
Publication Year: 2025
Collection: Repositório da Universidade Nova de Lisboa (UNL)
Subject Terms: Angola; antiretroviral therapy; drug resistance mutations; HIV-1; lenacapavir; molecular epidemiology; subtypes; Infectious Diseases; Virology; SDG 3 - Good Health and Well-being
Description: Funding Information: This research was funded in part by FCT\u2014Funda\u00E7\u00E3o para a Ci\u00EAncia e a Tecnologia, Minist\u00E9rio da Educa\u00E7\u00E3o e Ci\u00EAncia, Portugal, through funds to GHTM-UID/04413/2020, LA-REAL\u2014LA/P/0117/2020. Publisher Copyright: © 2025 by the authors. ; In 2023, the HIV-1 pandemic claimed around 630,000 lives worldwide due to AIDS-related complications. Its burden is significantly heavier in Sub-Saharan Africa, where an increased HIV-1 genetic diversity is common, which increases the risk of resistance to antiretroviral (ARV) drugs. This study aims to update the molecular epidemiology of HIV-1 in Angola, focusing specifically on the gag gene, which is often overlooked, and to assess the potential viability of lenacapavir (LEN)-based ARV therapy in the region. A total of 243 blood samples were collected from ARV-naïve, HIV-infected patients at the General Hospital of Benguela, city of Benguela, Angola. The capsid-encoding region of HIV-1 proviral DNA was amplified by PCR and sequenced. Phylogenetic analysis was performed using the maximum likelihood method, and genome recombinant forms were characterised through bootscanning analysis. Primary resistance mutations to LEN were identified using Stanford University’s HIVdb algorithm. Among the 80 successfully sequenced samples, 13 different genetic forms/subtypes were identified, with unique recombinant forms (URFs) (37.5%, 30/80) and subtype C (31.25%, 25/80) being the most prevalent. Regarding resistance mutations, none were detected, apart from four polymorphic mutations. These findings reinforce Angola’s position as a transitional HIV-1 hotspot between the genetically highly diverse Central Africa and the subtype C-dominated Southern Africa, while also supporting the potential effectiveness of LEN-based regimens for treatment and prevention of HIV-1 infections in the future. ; publishersversion ; published
Document Type: article in journal/newspaper
Language: English
ISBN: 978-0-01-496489-5; 0-01-496489-9
Relation: PURE: 118023040; Scopus: 105006789043; WOS: 001496489900001; PubMed: 40431722; PubMedCentral: PMC12116093; https://hdl.handle.net/10362/183975; https://doi.org/10.3390/v17050711
DOI: 10.3390/v17050711
Availability: https://hdl.handle.net/10362/183975; https://doi.org/10.3390/v17050711
Rights: openAccess
Accession Number: edsbas.46EDEFD8
Database: BASE