Effects of human leukocyte antigen class I genetic parameters on clinical outcomes and survival after initiation of highly active antiretroviral therapy

Background. Human leukocyte antigen (HLA) class I variation influences the progression of untreated human immunodeficiency virus (HIV) disease; however, it is not known whether HLA class I variation may influence clinical outcomes after initiation of highly active antiretroviral therapy (HAART). Methods. Associations between HLA class I genotypes and pretherapy clinical parameters were investigated in a cohort of 765 antiretroviral- naive adults initiating HAART. Cox proportional hazards regression was used to investigate the effects of HLA class I genotypes on time to suppression of the viral load to < 500 HIV RNA copies/ mL, time to an increase in the CD4 cell count to > 100 cells/mm(3) above the baseline count, and time to nonaccidental death over a > 5-year period after initiation of HAART. Results. Homozygosity at any HLA class I locus and possession of common HLA alleles were associated with a higher pretherapy viral load (P < .05). In multivariate analyses controlling for sociodemographic and clinical parameters at baseline, HLA class I homozygosity was significantly associated with a poorer CD4 cell response (P= .008), whereas possession of uncommon HLA alleles was associated with slower virologic suppression after initiation of HAART (P = .02). We observed no significant association between HLA parameters and time to nonaccidental death after initiation of HAART (P > .05 univariate analysis). Conclusion. HLA class I zygosity-dependent and frequency-dependent effects may influence short- termHAART outcomes, and, thus, they deserve further investigation. No effects of these HLA parameters on survival after initiation of HAART were observed.