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Variability in HIV-1 Integrase Gene and 3′-Polypurine Tract Sequences in Cameroon Clinical Isolates, and Implications for Integrase Inhibitors Efficacy

Integrase strand-transfer inhibitors (INSTIs) are now included in preferred first-line antiretroviral therapy (ART) for HIV-infected adults. Studies of Western clade-B HIV-1 show increased resistance to INSTIs following mutations in integrase and nef 3′polypurine tract (3′-PPT). With anticipated shi...

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Autores principales: Acharya, Arpan, Tagny, Claude T., Mbanya, Dora, Fonsah, Julius Y., Nchindap, Emilienne, Kenmogne, Léopoldine, Jihyun, Ma, Njamnshi, Alfred K., Kanmogne, Georgette D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7084836/
https://www.ncbi.nlm.nih.gov/pubmed/32106437
http://dx.doi.org/10.3390/ijms21051553
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author Acharya, Arpan
Tagny, Claude T.
Mbanya, Dora
Fonsah, Julius Y.
Nchindap, Emilienne
Kenmogne, Léopoldine
Jihyun, Ma
Njamnshi, Alfred K.
Kanmogne, Georgette D.
author_facet Acharya, Arpan
Tagny, Claude T.
Mbanya, Dora
Fonsah, Julius Y.
Nchindap, Emilienne
Kenmogne, Léopoldine
Jihyun, Ma
Njamnshi, Alfred K.
Kanmogne, Georgette D.
author_sort Acharya, Arpan
collection PubMed
description Integrase strand-transfer inhibitors (INSTIs) are now included in preferred first-line antiretroviral therapy (ART) for HIV-infected adults. Studies of Western clade-B HIV-1 show increased resistance to INSTIs following mutations in integrase and nef 3′polypurine tract (3′-PPT). With anticipated shifts in Africa (where 25.6-million HIV-infected people resides) to INSTIs-based ART, it is critical to monitor patients in African countries for resistance-associated mutations (RAMs) affecting INSTIs efficacy. We analyzed HIV-1 integrase and 3′-PPT sequences in 345 clinical samples from INSTIs-naïve HIV-infected Cameroonians for polymorphisms and RAMs that affect INSTIs. Phylogeny showed high genetic diversity, with the predominance of HIV-1 CRF02_AG. Major INSTIs RAMs T66A and N155K were found in two (0.6%) samples. Integrase polymorphic and accessory RAMs found included T97A, E157Q, A128T, M50I, S119R, L74M, L74I, S230N, and E138D (0.3′23.5% of samples). Ten (3.2%) samples had both I72V+L74M, L74M+T97A, or I72V+T97A mutations; thirty-one (9.8%) had 3′-PPT mutations. The low frequency of major INSTIs RAMs shows that INSTIs-based ART can be successfully used in Cameroon. Several samples had ≥1 INSTIs accessory RAMs known to reduce INSTIs efficacy; thus, INSTIs-based ART would require genetic surveillance. The 3′-PPT mutations could also affect INSTIs. For patients failing INSTIs-based ART with no INSTIs RAMs, monitoring 3′-PPT sequences could reveal treatment failure etiology.
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spelling pubmed-70848362020-03-23 Variability in HIV-1 Integrase Gene and 3′-Polypurine Tract Sequences in Cameroon Clinical Isolates, and Implications for Integrase Inhibitors Efficacy Acharya, Arpan Tagny, Claude T. Mbanya, Dora Fonsah, Julius Y. Nchindap, Emilienne Kenmogne, Léopoldine Jihyun, Ma Njamnshi, Alfred K. Kanmogne, Georgette D. Int J Mol Sci Article Integrase strand-transfer inhibitors (INSTIs) are now included in preferred first-line antiretroviral therapy (ART) for HIV-infected adults. Studies of Western clade-B HIV-1 show increased resistance to INSTIs following mutations in integrase and nef 3′polypurine tract (3′-PPT). With anticipated shifts in Africa (where 25.6-million HIV-infected people resides) to INSTIs-based ART, it is critical to monitor patients in African countries for resistance-associated mutations (RAMs) affecting INSTIs efficacy. We analyzed HIV-1 integrase and 3′-PPT sequences in 345 clinical samples from INSTIs-naïve HIV-infected Cameroonians for polymorphisms and RAMs that affect INSTIs. Phylogeny showed high genetic diversity, with the predominance of HIV-1 CRF02_AG. Major INSTIs RAMs T66A and N155K were found in two (0.6%) samples. Integrase polymorphic and accessory RAMs found included T97A, E157Q, A128T, M50I, S119R, L74M, L74I, S230N, and E138D (0.3′23.5% of samples). Ten (3.2%) samples had both I72V+L74M, L74M+T97A, or I72V+T97A mutations; thirty-one (9.8%) had 3′-PPT mutations. The low frequency of major INSTIs RAMs shows that INSTIs-based ART can be successfully used in Cameroon. Several samples had ≥1 INSTIs accessory RAMs known to reduce INSTIs efficacy; thus, INSTIs-based ART would require genetic surveillance. The 3′-PPT mutations could also affect INSTIs. For patients failing INSTIs-based ART with no INSTIs RAMs, monitoring 3′-PPT sequences could reveal treatment failure etiology. MDPI 2020-02-25 /pmc/articles/PMC7084836/ /pubmed/32106437 http://dx.doi.org/10.3390/ijms21051553 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Acharya, Arpan
Tagny, Claude T.
Mbanya, Dora
Fonsah, Julius Y.
Nchindap, Emilienne
Kenmogne, Léopoldine
Jihyun, Ma
Njamnshi, Alfred K.
Kanmogne, Georgette D.
Variability in HIV-1 Integrase Gene and 3′-Polypurine Tract Sequences in Cameroon Clinical Isolates, and Implications for Integrase Inhibitors Efficacy
title Variability in HIV-1 Integrase Gene and 3′-Polypurine Tract Sequences in Cameroon Clinical Isolates, and Implications for Integrase Inhibitors Efficacy
title_full Variability in HIV-1 Integrase Gene and 3′-Polypurine Tract Sequences in Cameroon Clinical Isolates, and Implications for Integrase Inhibitors Efficacy
title_fullStr Variability in HIV-1 Integrase Gene and 3′-Polypurine Tract Sequences in Cameroon Clinical Isolates, and Implications for Integrase Inhibitors Efficacy
title_full_unstemmed Variability in HIV-1 Integrase Gene and 3′-Polypurine Tract Sequences in Cameroon Clinical Isolates, and Implications for Integrase Inhibitors Efficacy
title_short Variability in HIV-1 Integrase Gene and 3′-Polypurine Tract Sequences in Cameroon Clinical Isolates, and Implications for Integrase Inhibitors Efficacy
title_sort variability in hiv-1 integrase gene and 3′-polypurine tract sequences in cameroon clinical isolates, and implications for integrase inhibitors efficacy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7084836/
https://www.ncbi.nlm.nih.gov/pubmed/32106437
http://dx.doi.org/10.3390/ijms21051553
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