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

Brumme ZL, Brumme CJ, Chui C, Mo T, Wynhoven B, Woods CK, Henrick BM, Hogg RS, Montaner JS, Harrigan PR

British Columbia Centre for Excellence in HIV/AIDS, Vancouver, BC, Canada.

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-term HAART outcomes, and, thus, they deserve further investigation. No effects of these HLA parameters on survival after initiation of HAART were observed.

Published 1 May 2007 in J Infect Dis, 195(11): 1694-704.
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