Research

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

Philippa J Easterbrook¹ , Mel Smith² , Jane Mullen³ , Siobhan O'Shea³ , Ian Chrystie³ , Annemiek de Ruiter³ , Iain D Tatt^4,6 , Anna Maria Geretti⁵ and Mark Zuckerman²

¹  Department of HIV/GU Medicine, King's College London School of Medicine at Guy's, King's College and St Thomas' hospitals, Weston Education Centre, 10 Cutcombe Road, London, SE5 9RJ, UK

²  Health Protection Agency London, London South Specialist Virology Centre, Bessemer Road, London, SE5 9RS, UK

³  Department of Virology and HIV/GU Medicine, St Thomas' Hospital, Westminster Bridge Road, London, SE1 7EH, UK

⁴  Virus Reference Department, Health Protection Agency, Centre for Infections, 61 Colindale Avenue, London, NW9 5HT, UK

⁵  Department of Virology, Royal Free Hospital and Royal Free and University College Medical School, Pond Street, London, NW3 2QG, UK

⁶  Pharmaceuticals Division, Hofffman-La Roche AG, Basel, Switzerland

author email corresponding author email

Journal of the International AIDS Society 2010, 13:4doi:10.1186/1758-2652-13-4

Published:	3 February 2010

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.