The prevalence of HIV-1 integrase mutations related to resistance to the next-generation integrase inhibitor (INI), dolutegravir (DTG), was assessed in 440 INI-naïve subjects and in 120 patients failing a raltegravir (RTG)-containing regimen. Of the mutations selected by DTG in vitro, S153FY was not detected in any isolate while L101I and T124A were highly prevalent in both groups and significantly associated with non-B subtype. RTG-selected double and triple mutants, mostly the G140S/Q148H variant, were detected in only 32 (26.7%) RTG-treated patients. As L101I and T124A do not appear to exert any major effect in vivo and double and triple mutants resistant to DTG are infrequently selected by RTG, DTG can be effectively used in INI-naïve patients and may retain activity in many patients failing RTG.
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http://dx.doi.org/10.1111/j.1469-0691.2012.03917.x | DOI Listing |
Viruses
December 2024
Global Health and Tropical Medicine, GHTM, Associate Laboratory in Translation and Innovation Towards Global Health, LA-REAL, Instituto de Higiene e Medicina Tropical, IHMT, Universidade NOVA de Lisboa, Rua da Junqueira 100, 1349-008 Lisboa, Portugal.
The high genetic variability of HIV-1 and the emergence of transmitted drug resistance (TDR) can impact treatment efficacy. In this study, we investigated the prevalent HIV-1 genotypes and drug-resistance-associated mutations in drug-naïve HIV-1 individuals in Cabo Verde. The study, conducted between 2018 and 2019, included drug-naïve HIV-1 individuals from the São Vicente, Boa Vista, Fogo, and Santiago islands.
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December 2024
Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Rua Waldemar Falcão, 121, Candeal, Salvador 40296-710, Bahia, Brazil.
The HIV-1 epidemic in Brazil is predominantly characterized by subtype B, except in the southern states, where subtype C (HIV-1C) is more prevalent. Continuous monitoring of this profile is essential to maintain an accurate understanding of the molecular landscape of the HIV epidemic in Brazil. In this study, we isolated and sequenced seven new HIV-1C strains from the state of Bahia, located in the Northeast region of Brazil.
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December 2024
HIV Pathogenesis Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2193, South Africa.
Islatravir (ISL) is the first-in-class nucleoside reverse transcriptase translocation inhibitor (NRTtI) with novel modes of action. Data on ISL resistance are currently limited, particularly to HIV-1 non-B subtypes. This study aimed to assess prevalent nucleos(t)ide reverse transcriptase inhibitor (NRTI)-resistant mutations in HIV-1 subtype C for their phenotypic resistance to ISL.
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November 2024
Institute of Biology, ELTE Eötvös Loránd University, 1117 Budapest, Hungary.
The increasingly widespread application of next-generation sequencing (NGS) in clinical diagnostics and epidemiological research has generated a demand for robust, fast, automated, and user-friendly bioinformatics workflows. To guide the choice of tools for the assembly of full-length viral genomes from NGS datasets, we assessed the performance and applicability of four open-source bioinformatics pipelines (shiver-for which we created a user-friendly Dockerized version, referred to as dshiver; SmaltAlign; viral-ngs; and V-pipe) using both simulated and real-world HIV-1 paired-end short-read datasets and default settings. All four pipelines produced consensus genome assemblies with high quality metrics (genome fraction recovery, mismatch and indel rates, variant calling F1 scores) when the reference sequence used for assembly had high similarity to the analyzed sample.
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November 2024
Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Avenida Professor Gama Pinto, 1649-003 Lisbon, Portugal.
This systematic review assessed the prevalence of transmitted and acquired HIV drug resistance (HIVDR) and the associated risk factors in Mozambique. A search of the PubMed, Cochrane, B-On, and Scopus databases up to December 2023 was conducted and included 11 studies with 1118 HIV-1 pol sequences. Drug resistance mutations (DRMs) to NNRTIs were found in 13% of the drug-naive individuals and 31% of those on ART, while NRTI resistance occurred in 5% and 10%, respectively.
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