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

Gall, Astrid, Kaye, Steve, Hue, Stephane, Bonsall, David, Rance, Richard, Baillie, Gregory J., Fidler, Sarah J., Weber, Jonathan N., McClure, Myra O., Kellam, Paul and SPARTAC Trial Investigators (2013) Restriction of V3 region sequence divergence in the HIV-1 envelope gene during antiretroviral treatment in a cohort of recent seroconverters. Retrovirology, 10 1: 8.1-8.15. doi:10.1186/1742-4690-10-8


Author Gall, Astrid
Kaye, Steve
Hue, Stephane
Bonsall, David
Rance, Richard
Baillie, Gregory J.
Fidler, Sarah J.
Weber, Jonathan N.
McClure, Myra O.
Kellam, Paul
SPARTAC Trial Investigators
Title Restriction of V3 region sequence divergence in the HIV-1 envelope gene during antiretroviral treatment in a cohort of recent seroconverters
Journal name Retrovirology   Check publisher's open access policy
ISSN 1742-4690
Publication date 2013-01
Sub-type Article (original research)
DOI 10.1186/1742-4690-10-8
Open Access Status DOI
Volume 10
Issue 1
Start page 8.1
End page 8.15
Total pages 15
Place of publication London, United Kingdom
Publisher BioMed Central
Collection year 2014
Language eng
Formatted 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.
Keyword HIV
Envelope
Deep sequencing
Primary infection
Diversity
Divergence
HAART
Short course antiretroviral therapy
AIDS
Coreceptor tropism
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Non HERDC
Institute for Molecular Bioscience - Publications
 
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Citation counts: TR Web of Science Citation Count  Cited 6 times in Thomson Reuters Web of Science Article | Citations
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Created: Fri, 14 Jun 2013, 11:16:02 EST by Gregory Baillie on behalf of Institute for Molecular Bioscience