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HLA B*5701 status, disease progression, and response to antiretroviral therapy

The UK Collaborative HIV Cohort Study Steering Committee

doi: 10.1097/01.aids.0000432613.95455.71
Clinical Science: Concise Communication

Objective: In addition to hypersensitivity reactions to abacavir, HLA B*5701 has been associated with slow or nonprogression of HIV infection. We explored the effect of HLA B*5701 on CD4+ cell count and viral load in untreated patients and on responses to nonabacavir-containing combination antiretroviral therapy (cART) in a large UK-based cohort.

Design: Analysis of a cohort of HIV-infected adults.

Methods: In untreated patients, CD4+ cell count and viral load at study entry were compared in HLAB*5701-positive and HLAB*5701-negative individuals and linear regression tested for an interaction effect of viral load and HLA B*5701 on CD4+ cell count. In patients starting a nonabacavir cART regimen, Cox proportional hazards models compared virological responses to cART among HLA B*5701-negative, HLA B*5701-positive, and those not tested. Six-month and 12-month changes in CD4+ cell count were used as outcomes in linear regression to compare immunological response to cART in these groups.

Results: ART-naive HLA B*5701-positive individuals had higher CD4+ cell count (P <0.0001) and lower viral load (P <0.0001) at study entry than negatives; however, HLA B*5701 status was not found to effect the association between viral load and CD4+ cell count (interaction P value = 0.09). HLA B*5701-positive patients were more likely to achieve viral suppression than negative patients on a nonabacavir regimen [hazard ratio = 1.29, 95% confidence interval, CI (1.15–1.54)] and less likely to experience viral rebound [hazard ratio = 0.61, 95% CI (0.37–0.99)].

Conclusion: Better virological but not immunological responses to cART were seen in HLA B*5701-positive patients on nonabacavir regimens. This study provides further evidence of the potentially beneficial effect of HLA B*5701 on HIV progression.

Research Department of Infection & Population Health, UCL, London, UK.

Correspondence to Miss Sophie Jose, HIV Epidemiology & Biostatistics Group, Research Department of Infection & Population Health, UCL, Floor 1, Royal Free Campus, London NW3 2PF, UK. Tel: +44207 794 0500 ext. 36763; e-mail: sophie.jose@ucl.ac.uk

This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivitives 3.0 License, where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially. http://creativecommons.org/licenses/by-nc-nd/3.0.

Received May 7, 2013

Accepted July 1, 2013

© 2013 Lippincott Williams & Wilkins, Inc.