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

OBJECTIVE: In addition to hypersensitivity reactions to abacavir, HLA B5701 has been associated with slow or nonprogression of HIV infection. We explored the effect of HLA B5701 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 HLAB5701-positive and HLAB5701-negative individuals and linear regression tested for an interaction effect of viral load and HLA B5701 on CD4 cell count. In patients starting a nonabacavir cART regimen, Cox proportional hazards models compared virological responses to cART among HLA B5701-negative, HLA B5701-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 B5701-positive individuals had higher CD4 cell count (P<0.0001) and lower viral load (P<0.0001) at study entry than negatives; however, HLA B5701 status was not found to effect the association between viral load and CD4 cell count (interaction P value=0.09). HLA B5701-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 B5701-positive patients on nonabacavir regimens. This study provides further evidence of the potentially beneficial effect of HLA B5701 on HIV progression.