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Restriction of V3 region sequence divergence in the HIV-1 envelope gene during antiretroviral treatment in a cohort of recent seroconverters

Title: Restriction of V3 region sequence divergence in the HIV-1 envelope gene during antiretroviral treatment in a cohort of recent seroconverters
Authors: Gall, A
Kaye, S
Hue, S
Bonsall, D
Rance, R
Baillie, GJ
Fidler, SJ
Weber, JN
McClure, MO
Kellam, P
Item Type: Journal Article
Abstract: Background: Dynamic changes in Human Immunodeficiency Virus 1 (HIV-1) sequence diversity and divergence are associated with immune control during primary infection and progression to AIDS. Consensus sequencing or single genome amplification sequencing of the HIV-1 envelope (env) gene, in particular the variable (V) regions, is used as a marker for HIV-1 genome diversity, but population diversity is only minimally, or semi-quantitatively sampled using these methods. Results: Here we use second generation deep sequencing to determine inter-and intra-patient sequence heterogeneity and to quantify minor variants in a cohort of individuals either receiving or not receiving antiretroviral treatment following seroconversion; the SPARTAC trial. We show, through a cross-sectional study of sequence diversity of the env V3 in 30 antiretroviral-naive patients during primary infection that considerable population structure diversity exists, with some individuals exhibiting highly constrained plasma virus diversity. Diversity was independent of clinical markers (viral load, time from seroconversion, CD4 cell count) of infection. Serial sampling over 60 weeks of non-treated individuals that define three initially different diversity profiles showed that complex patterns of continuing HIV-1 sequence diversification and divergence could be readily detected. Evidence for minor sequence turnover, emergence of new variants and re-emergence of archived variants could be inferred from this analysis. Analysis of viral divergence over the same time period in patients who received short (12 weeks, ART12) or long course antiretroviral therapy (48 weeks, ART48) and a non-treated control group revealed that ART48 successfully suppressed viral divergence while ART12 did not have a significant effect. Conclusions: Deep sequencing is a sensitive and reliable method for investigating the diversity of the env V3 as an important component of HIV-1 genome diversity. Detailed insights into the complex early intra-patient dynamics of env V3 diversity and divergence were explored in antiretroviral-naïve recent seroconverters. Long course antiretroviral therapy, initiated soon after seroconversion and administered for 48 weeks, restricts HIV-1 divergence significantly. The effect of ART12 and ART48 on clinical markers of HIV infection and progression is currently investigated in the SPARTAC trial.
Issue Date: 18-Jan-2013
Date of Acceptance: 27-Apr-2012
URI: http://hdl.handle.net/10044/1/49837
DOI: https://dx.doi.org/10.1186/1742-4690-10-8
ISSN: 1742-4690
Publisher: BioMed Central
Journal / Book Title: Retrovirology
Volume: 10
Copyright Statement: © 2013 Gall et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Sponsor/Funder: National Institute for Health Research
Funder's Grant Number: NF-SI-0507-10313
Keywords: Science & Technology
Life Sciences & Biomedicine
Virology
VIROLOGY
HIV
Envelope
Deep sequencing
Primary infection
Diversity
Divergence
HAART
Short course antiretroviral therapy
AIDS
Coreceptor tropism
VIRUS TYPE-1 ENV
CORECEPTOR USAGE
INFECTION
THERAPY
DNA
IDENTIFICATION
RECOMBINATION
EVOLUTION
BREAKPOINTS
PREDICTION
Antiretroviral Therapy, Highly Active
Cohort Studies
Cross-Sectional Studies
Genes, env
Genetic Variation
HIV Antibodies
HIV Envelope Protein gp120
HIV Infections
HIV-1
Humans
Mutation
Peptide Fragments
Sequence Analysis, DNA
Time Factors
Treatment Outcome
SPARTAC Trial Investigators
1103 Clinical Sciences
Publication Status: Published
Article Number: ARTN 8
Appears in Collections:Department of Medicine
Faculty of Medicine



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