Drug Resistance Mutations Against Protease, Reverse Transcriptase and Integrase Inhibitors in People Living With HIV-1 Receiving Boosted Protease Inhibitors in South Africa.

Autor:	Obasa AE; Division of Medical Virology, Department of Pathology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.; Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institute, Stockholm University, Stockholm, Sweden., Mikasi SG; Division of Medical Virology, Department of Pathology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa., Brado D; Division of Virology, Institute for Virology and Immunobiology, Faculty of Medicine, University of Würzburg, Würzburg, Germany., Cloete R; South African Medical Research Council Bioinformatics Unit, South African National Bioinformatics Institute, University of the Western Cape, Bellville, South Africa., Singh K; Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institute, Stockholm University, Stockholm, Sweden.; Department of Molecular Microbiology and Immunology, University of Missouri, Columbia, MO, United States.; Christopher S. Bond Life Sciences Center, University of Missouri, Columbia, MO, United States., Neogi U; Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institute, Stockholm University, Stockholm, Sweden., Jacobs GB; Division of Medical Virology, Department of Pathology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
Jazyk:	angličtina
Zdroj:	Frontiers in microbiology [Front Microbiol] 2020 Mar 20; Vol. 11, pp. 438. Date of Electronic Publication: 2020 Mar 20 (Print Publication: 2020).
DOI:	10.3389/fmicb.2020.00438
Abstrakt:	The South African national combination antiretroviral therapy (cART) roll-out program started in 2006, with over 4.4 million people accessing treatment since it was first introduced. HIV-1 drug resistance can hamper the success of cART. This study determined the patterns of HIV-1 drug-resistance associated mutations (RAMs) in People Living with HIV-1 (PLHIV-1). Receiving first (for children below 3 years of age) and second-line (for adults) cART regimens in South Africa. During 2017 and 2018, 110 patients plasma samples were selected, 96 samples including those of 17 children and infants were successfully analyzed. All patients were receiving a boosted protease inhibitor (bPI) as part of their cART regimen. The viral sequences were analyzed for RAMs through genotypic resistance testing. We performed genotypic resistance testing (GRT) for Protease inhibitors (PIs), Reverse transcriptase inhibitors (RTIs) and Integrase strand transfer inhibitors (InSTIs). Viral sequences were subtyped using REGAv3 and COMET. Based on the PR/RT sequences, HIV-1 subtypes were classified as 95 (99%) HIV-1 subtype C (HIV-1C) while one sample as 02_AG. Integrase sequencing was successful for 89 sequences, and all the sequences were classified as HIV-1C (99%, 88/89) except one sequence classified CRF02_AG, as observed in PR/RT. Of the 96 PR/RT sequences analyzed, M184V/I (52/96; 54%) had the most frequent RAM nucleoside reverse transcriptase inhibitor (NRTI). The most frequent non-nucleoside reverse transcriptase inhibitor (NNRTI) RAM was K103N/S (40/96, 42%). Protease inhibitor (PI) RAMs M46I and V82A were present in 12 (13%) of the sequences analyzed. Among the InSTI major RAM two (2.2%) sequences have Y143R and T97A mutations while one sample had T66I. The accessory RAM E157Q was identified in two (2.2%). The data indicates that the majority of the patients failed on bPIs didn't have any mutation; therefore adherence could be major issue in these groups of individuals. We propose continued viral load monitoring for better management of infected PLHIV. (Copyright © 2020 Obasa, Mikasi, Brado, Cloete, Singh, Neogi and Jacobs.)
Databáze:	MEDLINE
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