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

Journal of the International AIDS Society - 2010
Philippa Easterbrook1, Mel Smith2, Jane Mullen3, Siobhan O’Shea3, I. L. Chrystie3, Annemiek de Ruiter3, Iain Tatt4,5, Anna María Geretti6, Mark Zuckerman2
1Department 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
2Health Protection Agency London, London South Specialist Virology Centre, Bessemer Road, London, SE5 9RS, UK
3Department of Virology and HIV/GU Medicine, St Thomas' Hospital, Westminster Bridge Road, London, SE1 7EH, UK
4Pharmaceuticals Division, Hofffman-La Roche AG, Basel, Switzerland
5Virus Reference Department, Health Protection Agency, Centre for Infections, 61 Colindale Avenue, London, NW9 5HT, UK
6Department of Virology, Royal Free Hospital and Royal Free and University College Medical School, Pond Street, London, NW3 2QG, UK

Tóm tắt

BackgroundOur 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.MethodsA 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.ResultsComplete 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)ConclusionsThis 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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Journal of the International AIDS Society

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