114 SPECIFIC HLA-B ALLELES KNOWN TO INFLUENCE UNTREATED HIV-1 DISEASE PROGRESSION DO NOT APPEAR TO AFFECT RESPONSE TO HIGHLY ACTIVE ANTIRETROVIRAL THERAPY CJ Brumme1, C Chui1, C Woods1, B Wynhoven1, R Hogg2, J Montaner2, PR Harrigan2, ZL Brumme2 Background: Host genetic variation within the HLA-B locus influences untreated HIV disease progression. Specifically, HLA-B*5701 and B*27 are associated with protective effects, whereas HLA-B*35Px (comprising B*3502,*3503,*3504 and *5301) and B22 serogroup (comprising B*54, *55 and *56) are associated with disease progression. We investigated associations between these HLA-B alleles and therapeutic outcomes in a cohort of 765 antiretroviral-naive individuals initiating HAART.
1BC Centre for Excellence in HIV/AIDS; 2BC Centre for Excellence in HIV/AIDS, Faculty of Medicine -University of British Columbia, Vancouver, British Columbia
Methods: HLA-B sequence-based typing of study subjects (N=765) was performed with a validated protocol. Alleles were resolved to intermediate-level resolution. Associations between HLA-B alleles and baseline (pre-therapy) parameters were investigated in a cross-sectional analysis. Cox proportional hazards regression was used to investigate the effect of HLA-B alleles on therapeutic outcomes. Endpoints included time to pVL suppression below 500 copies/ml, subsequent time to pVL rebound, time to CD4 decline below baseline, and time to non-accidental death.
Results: HLA-B*5701, B*27, B*35Px and B22 alleles were observed in N=47, 52, 37 and 39 individuals, respectively. At baseline, HLA-B*5701 was associated with significantly lower pVL (p=0.001) whereas B22 was associated with higher pVL (p=0.02). No significant differences in baseline CD4 counts were observed. In multivariate analyses controlling for baseline parameters, initial therapy type, adherence estimates, and other host and viral genetic markers of HIV disease progression, we observed no significant association between these HLA-B alleles and virologic or immunologic treatment outcomes, or survival following HAART initiation (p>0.05). Of interest, the B*35Py alleles (comprising B*3501 and B*3508) (N=62) were significantly associated with poorer immunological response and decreased survival following HAART initiation (multivariate p<0.01).
Conclusion: Alleles HLA-B*5701, B*27, B22 and B*35Px appear to have no influence on therapeutic outcomes in individuals initiating HAART. The association between B*35Py alleles and poorer therapeutic outcomes suggests that HAART outcomes may be influenced by a different set of HLA-B alleles than untreated outcomes.