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Journal of the International AIDS Society
Published in: Journal of the International AIDS Society 1/2010

Open Access 01-12-2010 | Research

Impact of HIV-1 viral subtype on disease progression and response to antiretroviral therapy

Authors: Philippa J Easterbrook, Mel Smith, Jane Mullen, Siobhan O'Shea, Ian Chrystie, Annemiek de Ruiter, Iain D Tatt, Anna Maria Geretti, Mark Zuckerman

Published in: Journal of the International AIDS Society | Issue 1/2010

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Abstract

Background

Our intention was to compare the rate of immunological progression prior to antiretroviral therapy (ART) and the virological response to ART in patients infected with subtype B and four non-B HIV-1 subtypes (A, C, D and the circulating recombinant form, CRF02-AG) in an ethnically diverse population of HIV-1-infected patients in south London.

Methods

A random sample of 861 HIV-1-infected patients attending HIV clinics at King's and St Thomas' hospitals' were subtyped using an in-house enzyme-linked immunoassay and env sequencing. Subtypes were compared on the rate of CD4 cell decline using a multi-level random effects model. Virological response to ART was compared using the time to virological suppression (< 400 copies/ml) and rate of virological rebound (> 400 copies/ml) following initial suppression.

Results

Complete subtype and epidemiological data were available for 679 patients, of whom 357 (52.6%) were white and 230 (33.9%) were black African. Subtype B (n = 394) accounted for the majority of infections, followed by subtypes C (n = 125), A (n = 84), D (n = 51) and CRF02-AG (n = 25). There were no significant differences in rate of CD4 cell decline, initial response to highly active antiretroviral therapy and subsequent rate of virological rebound for subtypes B, A, C and CRF02-AG. However, a statistically significant four-fold faster rate of CD4 decline (after adjustment for gender, ethnicity and baseline CD4 count) was observed for subtype D. In addition, subtype D infections showed a higher rate of virological rebound at six months (70%) compared with subtypes B (45%, p = 0.02), A (35%, p = 0.004) and C (34%, p = 0.01)

Conclusions

This is the first study from an industrialized country to show a faster CD4 cell decline and higher rate of subsequent virological failure with subtype D infection. Further studies are needed to identify the molecular mechanisms responsible for the greater virulence of subtype D.
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Metadata
Title
Impact of HIV-1 viral subtype on disease progression and response to antiretroviral therapy
Authors
Philippa J Easterbrook
Mel Smith
Jane Mullen
Siobhan O'Shea
Ian Chrystie
Annemiek de Ruiter
Iain D Tatt
Anna Maria Geretti
Mark Zuckerman
Publication date
01-12-2010
Publisher
BioMed Central
Published in
Journal of the International AIDS Society / Issue 1/2010
Electronic ISSN: 1758-2652
DOI
https://doi.org/10.1186/1758-2652-13-4

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