Human leukocyte antigen class I supertypes and HIV-1 control in African Americans

Aleksandr Lazaryan, Wei Song, Elena Lobashevsky, Jianming Tang, Sadeep Shrestha, Kui Zhang, Lytt I. Gardner, Janet M. McNicholl, Craig M. Wilson, Robert S. Klein, Anne Rompalo, Kenneth Mayer, Jack Sobel, Richard A. Kaslow

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23 Scopus citations

Abstract

The role of human leukocyte antigen (HLA) class I supertypes in controlling human immunodeficiency virus type 1 (HIV-1) infection in African Americans has not been established. We examined the effects of the HLA-A and HLA-B alleles and supertypes on the outcomes of HIV-1 clade B infection among 338 African American women and adolescents. HLA-B58 and -B62 supertypes (B58s and B62s) were associated with favorable HIV-1 disease control (proportional odds ratio [POR] of 0.33 and 95% confidence interval [95% CI] of 0.21 to 0.52 for the former and POR of 0.26 and 95% CI of 0.09 to 0.73 for the latter); B7s and B44s were associated with unfavorable disease control (POR of 2.39 and 95% CI of 1.54 to 3.73 for the former and POR of 1.63 and 95% CI of 1.08 to 2.47 for the latter). In general, individual alleles within specific B supertypes exerted relatively homogeneous effects. A notable exception was B27s, whose protective influence (POR, 0.58; 95% CI, 0.35 to 0.94) was masked by the opposing effect of its member allele B*1510. The associations of most B supertypes (e.g., B58s and B7s) were largely explained either by well-known effects of constituent B alleles or by effects of previously unimplicated B alleles aggregated into a particular supertype (e.g., B44s and B62s). A higher frequency of HLA-B genotypic supertypes correlated with a higher mean viral load (VL) and lower mean CD4 count (Pearson's r = 0.63 and 0.62, respectively; P = 0.03). Among the genotypic supertypes, B58s and its member allele B*57 contributed disproportionately to the explainable VL variation. The study demonstrated the dominant role of HLA-B supertypes in HIV-1 clade B-infected African Americans and further dissected the contributions of individual class I alleles and their population frequencies to the supertype effects.

Original languageEnglish (US)
Pages (from-to)2610-2617
Number of pages8
JournalJournal of virology
Volume84
Issue number5
DOIs
StatePublished - Mar 2010

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    Lazaryan, A., Song, W., Lobashevsky, E., Tang, J., Shrestha, S., Zhang, K., Gardner, L. I., McNicholl, J. M., Wilson, C. M., Klein, R. S., Rompalo, A., Mayer, K., Sobel, J., & Kaslow, R. A. (2010). Human leukocyte antigen class I supertypes and HIV-1 control in African Americans. Journal of virology, 84(5), 2610-2617. https://doi.org/10.1128/JVI.01962-09