HIV-1 Gag gene mutations, treatment response and drug resistance to protease inhibitors: A systematic review and meta-analysis protocol.

<h4>Background</h4>Some mutations in the HIV-1 Gag gene are known to confer resistance to ritonavir-boosted protease inhibitors (PI/r), but their clinical implications remain controversial. This review aims at summarizing current knowledge on HIV-1 Gag gene mutations that are selected un...

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Autores principales:	Alex Durand Nka, Georges Teto, Maria Mercedes Santoro, Valantine Ngum Ndze, Désiré Takou, Beatrice Dambaya, Ezechiel Ngoufack Jagni Semengue, Lavinia Fabeni, Carlo-Federico Perno, Vittorio Colizzi, Francesca Ceccherini-Silberstein, Joseph Fokam
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/46632ce0566b4e68b52f7803d71e690d
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spelling	oai:doaj.org-article:46632ce0566b4e68b52f7803d71e690d2021-12-02T20:09:48ZHIV-1 Gag gene mutations, treatment response and drug resistance to protease inhibitors: A systematic review and meta-analysis protocol.1932-620310.1371/journal.pone.0253587https://doaj.org/article/46632ce0566b4e68b52f7803d71e690d2021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0253587https://doaj.org/toc/1932-6203<h4>Background</h4>Some mutations in the HIV-1 Gag gene are known to confer resistance to ritonavir-boosted protease inhibitors (PI/r), but their clinical implications remain controversial. This review aims at summarizing current knowledge on HIV-1 Gag gene mutations that are selected under PI/r pressure and their distribution according to viral subtypes.<h4>Materials and methods</h4>Randomized and non-randomized trials, cohort and cross-sectional studies evaluating HIV-1 Gag gene mutations and protease resistance associated mutations, will all be included. Searches will be conducted (from January 2000 onwards) in PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Latin American and Caribbean Health Sciences Literature (LILAC), Web of Science, African Journals Online, and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases. Hand searching of the reference lists of relevant reviews and trials will be conducted and we will also look for conference abstracts. Genotypic profiles of both Gag gene and the protease region as well as viral subtypes (especially B vs. non B) will all serve as comparators. Primary outcomes will be the "prevalence of Gag mutations" and the "prevalence of PI/r resistance associated mutations". Secondary outcomes will be the "rate of treatment failure" and the distribution of Gag mutations according to subtypes. Two reviewers will independently screen titles and abstracts, assess the full texts for eligibility, and extract data. If data permits, random effects models will be used where appropriate. This study will be reported according to the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta Analyses.<h4>Discussion</h4>This systematic review will help identify HIV-1 Gag gene mutations associated to PI/r-based regimen according to viral subtypes. Findings of this review will help to better understand the implications of the Gag gene mutations in PI/r treatment failure. This may later justify considerations of Gag-genotyping within HIV drug resistance interpretation algorithms in the clinical management of patients receiving PI/r regimens.<h4>Systematic review registration</h4>PROSPERO: CRD42019114851.Alex Durand NkaGeorges TetoMaria Mercedes SantoroValantine Ngum NdzeDésiré TakouBeatrice DambayaEzechiel Ngoufack Jagni SemengueLavinia FabeniCarlo-Federico PernoVittorio ColizziFrancesca Ceccherini-SilbersteinJoseph FokamPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 7, p e0253587 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Alex Durand Nka Georges Teto Maria Mercedes Santoro Valantine Ngum Ndze Désiré Takou Beatrice Dambaya Ezechiel Ngoufack Jagni Semengue Lavinia Fabeni Carlo-Federico Perno Vittorio Colizzi Francesca Ceccherini-Silberstein Joseph Fokam HIV-1 Gag gene mutations, treatment response and drug resistance to protease inhibitors: A systematic review and meta-analysis protocol.
description	<h4>Background</h4>Some mutations in the HIV-1 Gag gene are known to confer resistance to ritonavir-boosted protease inhibitors (PI/r), but their clinical implications remain controversial. This review aims at summarizing current knowledge on HIV-1 Gag gene mutations that are selected under PI/r pressure and their distribution according to viral subtypes.<h4>Materials and methods</h4>Randomized and non-randomized trials, cohort and cross-sectional studies evaluating HIV-1 Gag gene mutations and protease resistance associated mutations, will all be included. Searches will be conducted (from January 2000 onwards) in PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Latin American and Caribbean Health Sciences Literature (LILAC), Web of Science, African Journals Online, and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases. Hand searching of the reference lists of relevant reviews and trials will be conducted and we will also look for conference abstracts. Genotypic profiles of both Gag gene and the protease region as well as viral subtypes (especially B vs. non B) will all serve as comparators. Primary outcomes will be the "prevalence of Gag mutations" and the "prevalence of PI/r resistance associated mutations". Secondary outcomes will be the "rate of treatment failure" and the distribution of Gag mutations according to subtypes. Two reviewers will independently screen titles and abstracts, assess the full texts for eligibility, and extract data. If data permits, random effects models will be used where appropriate. This study will be reported according to the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta Analyses.<h4>Discussion</h4>This systematic review will help identify HIV-1 Gag gene mutations associated to PI/r-based regimen according to viral subtypes. Findings of this review will help to better understand the implications of the Gag gene mutations in PI/r treatment failure. This may later justify considerations of Gag-genotyping within HIV drug resistance interpretation algorithms in the clinical management of patients receiving PI/r regimens.<h4>Systematic review registration</h4>PROSPERO: CRD42019114851.
format	article
author	Alex Durand Nka Georges Teto Maria Mercedes Santoro Valantine Ngum Ndze Désiré Takou Beatrice Dambaya Ezechiel Ngoufack Jagni Semengue Lavinia Fabeni Carlo-Federico Perno Vittorio Colizzi Francesca Ceccherini-Silberstein Joseph Fokam
author_facet	Alex Durand Nka Georges Teto Maria Mercedes Santoro Valantine Ngum Ndze Désiré Takou Beatrice Dambaya Ezechiel Ngoufack Jagni Semengue Lavinia Fabeni Carlo-Federico Perno Vittorio Colizzi Francesca Ceccherini-Silberstein Joseph Fokam
author_sort	Alex Durand Nka
title	HIV-1 Gag gene mutations, treatment response and drug resistance to protease inhibitors: A systematic review and meta-analysis protocol.
title_short	HIV-1 Gag gene mutations, treatment response and drug resistance to protease inhibitors: A systematic review and meta-analysis protocol.
title_full	HIV-1 Gag gene mutations, treatment response and drug resistance to protease inhibitors: A systematic review and meta-analysis protocol.
title_fullStr	HIV-1 Gag gene mutations, treatment response and drug resistance to protease inhibitors: A systematic review and meta-analysis protocol.
title_full_unstemmed	HIV-1 Gag gene mutations, treatment response and drug resistance to protease inhibitors: A systematic review and meta-analysis protocol.
title_sort	hiv-1 gag gene mutations, treatment response and drug resistance to protease inhibitors: a systematic review and meta-analysis protocol.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/46632ce0566b4e68b52f7803d71e690d
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HIV-1 Gag gene mutations, treatment response and drug resistance to protease inhibitors: A systematic review and meta-analysis protocol.

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