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Highly prevalent Russian HIV-1 V3-loop sequence variants are susceptible to maraviroc

INTRODUCTION: Maraviroc inhibits CCR5-tropic HIV-1 across different subtypes in vitro and has demonstrated efficacy in clinical trials. V3-loop amino acid variants observed in individual maraviroc-resistant viruses have not been found to be predictive of reduced susceptibility. Sequence-database sea...

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Autores principales: Lewis, ME, Jubb, B, Simpson, P, Lopatukhin, A, Kireev, D, Bobkova, M, Craig, C, van der Ryst, E, Westby, M, Butler, SL
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8236768/
https://www.ncbi.nlm.nih.gov/pubmed/34160290
http://dx.doi.org/10.1177/20402066211025156
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author Lewis, ME
Jubb, B
Simpson, P
Lopatukhin, A
Kireev, D
Bobkova, M
Craig, C
van der Ryst, E
Westby, M
Butler, SL
author_facet Lewis, ME
Jubb, B
Simpson, P
Lopatukhin, A
Kireev, D
Bobkova, M
Craig, C
van der Ryst, E
Westby, M
Butler, SL
author_sort Lewis, ME
collection PubMed
description INTRODUCTION: Maraviroc inhibits CCR5-tropic HIV-1 across different subtypes in vitro and has demonstrated efficacy in clinical trials. V3-loop amino acid variants observed in individual maraviroc-resistant viruses have not been found to be predictive of reduced susceptibility. Sequence-database searches have demonstrated that approximately 7.3% of viruses naturally encode these variants, raising concerns regarding potential pre-existing resistance. A study from Russia reported that combinations of these same amino acids are present in the V3 loops of the Russian variant subtype A (IDU-A, now A6) with a much greater prevalence (range: 74.4%–92.3%) depending on the combination. However, these studies and database searches did not include phenotypic evaluation. METHODS: Sixteen Russian HIV-1 isolates (including sub-subtype A6 viruses) were assessed for V3 loop sequence and phenotypic susceptibility to maraviroc. RESULTS: All 12 of the A6 viruses and 2/4 subtype B isolates encoded V3-loop variants that have previously been identified in individual virus isolates with reduced susceptibility to maraviroc. However, despite the prevalence of these V3-loop amino acid variants among the tested viruses, phenotypic sensitivity to maraviroc was observed in all instances. Similarly, reduced susceptibility to maraviroc was not found in virus from participants who experienced virologic failure in a clinical study of maraviroc in Russia (A4001101, [NCT01275625]). DISCUSSION: Altogether, these data confirm that the presence of individual or combinations of V3-loop amino acid residues in sub-subtype A6 viruses alone does not predict natural resistance to maraviroc and that V3-loop genotype analysis of R5 virus prior to treatment is not helpful in predicting clinical outcome.
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spelling pubmed-82367682021-07-08 Highly prevalent Russian HIV-1 V3-loop sequence variants are susceptible to maraviroc Lewis, ME Jubb, B Simpson, P Lopatukhin, A Kireev, D Bobkova, M Craig, C van der Ryst, E Westby, M Butler, SL Antivir Chem Chemother Short Communication INTRODUCTION: Maraviroc inhibits CCR5-tropic HIV-1 across different subtypes in vitro and has demonstrated efficacy in clinical trials. V3-loop amino acid variants observed in individual maraviroc-resistant viruses have not been found to be predictive of reduced susceptibility. Sequence-database searches have demonstrated that approximately 7.3% of viruses naturally encode these variants, raising concerns regarding potential pre-existing resistance. A study from Russia reported that combinations of these same amino acids are present in the V3 loops of the Russian variant subtype A (IDU-A, now A6) with a much greater prevalence (range: 74.4%–92.3%) depending on the combination. However, these studies and database searches did not include phenotypic evaluation. METHODS: Sixteen Russian HIV-1 isolates (including sub-subtype A6 viruses) were assessed for V3 loop sequence and phenotypic susceptibility to maraviroc. RESULTS: All 12 of the A6 viruses and 2/4 subtype B isolates encoded V3-loop variants that have previously been identified in individual virus isolates with reduced susceptibility to maraviroc. However, despite the prevalence of these V3-loop amino acid variants among the tested viruses, phenotypic sensitivity to maraviroc was observed in all instances. Similarly, reduced susceptibility to maraviroc was not found in virus from participants who experienced virologic failure in a clinical study of maraviroc in Russia (A4001101, [NCT01275625]). DISCUSSION: Altogether, these data confirm that the presence of individual or combinations of V3-loop amino acid residues in sub-subtype A6 viruses alone does not predict natural resistance to maraviroc and that V3-loop genotype analysis of R5 virus prior to treatment is not helpful in predicting clinical outcome. SAGE Publications 2021-06-23 /pmc/articles/PMC8236768/ /pubmed/34160290 http://dx.doi.org/10.1177/20402066211025156 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by-nc/4.0/Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).
spellingShingle Short Communication
Lewis, ME
Jubb, B
Simpson, P
Lopatukhin, A
Kireev, D
Bobkova, M
Craig, C
van der Ryst, E
Westby, M
Butler, SL
Highly prevalent Russian HIV-1 V3-loop sequence variants are susceptible to maraviroc
title Highly prevalent Russian HIV-1 V3-loop sequence variants are susceptible to maraviroc
title_full Highly prevalent Russian HIV-1 V3-loop sequence variants are susceptible to maraviroc
title_fullStr Highly prevalent Russian HIV-1 V3-loop sequence variants are susceptible to maraviroc
title_full_unstemmed Highly prevalent Russian HIV-1 V3-loop sequence variants are susceptible to maraviroc
title_short Highly prevalent Russian HIV-1 V3-loop sequence variants are susceptible to maraviroc
title_sort highly prevalent russian hiv-1 v3-loop sequence variants are susceptible to maraviroc
topic Short Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8236768/
https://www.ncbi.nlm.nih.gov/pubmed/34160290
http://dx.doi.org/10.1177/20402066211025156
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