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High Level of Pre-Treatment HIV-1 Drug Resistance and Its Association with HLA Class I-Mediated Restriction in the Pumwani Sex Worker Cohort

Background: We analyzed the prevalence of pre-antiretroviral therapy (ART) drug resistance mutations (DRMs) in a Kenyan population. We also examined whether host HLA class I genes influence the development of pre-ART DRMs. Methods: The HIV-1 proviral DNAs were amplified from blood samples of 266 ART...

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Autores principales: Willim, Rachel, Shadabi, Elnaz, Sampathkumar, Raghavan, Li, Lin, Balshaw, Robert, Kimani, Joshua, Plummer, Francis A., Luo, Ma, Liang, Binhua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8879707/
https://www.ncbi.nlm.nih.gov/pubmed/35215866
http://dx.doi.org/10.3390/v14020273
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author Willim, Rachel
Shadabi, Elnaz
Sampathkumar, Raghavan
Li, Lin
Balshaw, Robert
Kimani, Joshua
Plummer, Francis A.
Luo, Ma
Liang, Binhua
author_facet Willim, Rachel
Shadabi, Elnaz
Sampathkumar, Raghavan
Li, Lin
Balshaw, Robert
Kimani, Joshua
Plummer, Francis A.
Luo, Ma
Liang, Binhua
author_sort Willim, Rachel
collection PubMed
description Background: We analyzed the prevalence of pre-antiretroviral therapy (ART) drug resistance mutations (DRMs) in a Kenyan population. We also examined whether host HLA class I genes influence the development of pre-ART DRMs. Methods: The HIV-1 proviral DNAs were amplified from blood samples of 266 ART-naïve women from the Pumwani Sex Worker cohort of Nairobi, Kenya using a nested PCR method. The amplified HIV genomes were sequenced using next-generation sequencing technology. The prevalence of pre-ART DRMs was investigated. Correlation studies were performed between HLA class I alleles and HIV-1 DRMs. Results: Ninety-eight percent of participants had at least one DRM, while 38% had at least one WHO surveillance DRM. M184I was the most prevalent clinically important variant, seen in 37% of participants. The DRMs conferring resistance to one or more integrase strand transfer inhibitors were also found in up to 10% of participants. Eighteen potentially relevant (p < 0.05) positive correlations were found between HLA class 1 alleles and HIV drug-resistant variants. Conclusions: High levels of HIV drug resistance were found in all classes of antiretroviral drugs included in the current first-line ART regimens in Africa. The development of DRMs may be influenced by host HLA class I-restricted immunity.
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spelling pubmed-88797072022-02-26 High Level of Pre-Treatment HIV-1 Drug Resistance and Its Association with HLA Class I-Mediated Restriction in the Pumwani Sex Worker Cohort Willim, Rachel Shadabi, Elnaz Sampathkumar, Raghavan Li, Lin Balshaw, Robert Kimani, Joshua Plummer, Francis A. Luo, Ma Liang, Binhua Viruses Article Background: We analyzed the prevalence of pre-antiretroviral therapy (ART) drug resistance mutations (DRMs) in a Kenyan population. We also examined whether host HLA class I genes influence the development of pre-ART DRMs. Methods: The HIV-1 proviral DNAs were amplified from blood samples of 266 ART-naïve women from the Pumwani Sex Worker cohort of Nairobi, Kenya using a nested PCR method. The amplified HIV genomes were sequenced using next-generation sequencing technology. The prevalence of pre-ART DRMs was investigated. Correlation studies were performed between HLA class I alleles and HIV-1 DRMs. Results: Ninety-eight percent of participants had at least one DRM, while 38% had at least one WHO surveillance DRM. M184I was the most prevalent clinically important variant, seen in 37% of participants. The DRMs conferring resistance to one or more integrase strand transfer inhibitors were also found in up to 10% of participants. Eighteen potentially relevant (p < 0.05) positive correlations were found between HLA class 1 alleles and HIV drug-resistant variants. Conclusions: High levels of HIV drug resistance were found in all classes of antiretroviral drugs included in the current first-line ART regimens in Africa. The development of DRMs may be influenced by host HLA class I-restricted immunity. MDPI 2022-01-28 /pmc/articles/PMC8879707/ /pubmed/35215866 http://dx.doi.org/10.3390/v14020273 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Willim, Rachel
Shadabi, Elnaz
Sampathkumar, Raghavan
Li, Lin
Balshaw, Robert
Kimani, Joshua
Plummer, Francis A.
Luo, Ma
Liang, Binhua
High Level of Pre-Treatment HIV-1 Drug Resistance and Its Association with HLA Class I-Mediated Restriction in the Pumwani Sex Worker Cohort
title High Level of Pre-Treatment HIV-1 Drug Resistance and Its Association with HLA Class I-Mediated Restriction in the Pumwani Sex Worker Cohort
title_full High Level of Pre-Treatment HIV-1 Drug Resistance and Its Association with HLA Class I-Mediated Restriction in the Pumwani Sex Worker Cohort
title_fullStr High Level of Pre-Treatment HIV-1 Drug Resistance and Its Association with HLA Class I-Mediated Restriction in the Pumwani Sex Worker Cohort
title_full_unstemmed High Level of Pre-Treatment HIV-1 Drug Resistance and Its Association with HLA Class I-Mediated Restriction in the Pumwani Sex Worker Cohort
title_short High Level of Pre-Treatment HIV-1 Drug Resistance and Its Association with HLA Class I-Mediated Restriction in the Pumwani Sex Worker Cohort
title_sort high level of pre-treatment hiv-1 drug resistance and its association with hla class i-mediated restriction in the pumwani sex worker cohort
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8879707/
https://www.ncbi.nlm.nih.gov/pubmed/35215866
http://dx.doi.org/10.3390/v14020273
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