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Journal of Virology, August 2002, p. 8276-8284, Vol. 76, No. 16
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.16.8276-8284.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Favorable and Unfavorable HLA Class I Alleles and Haplotypes in Zambians Predominantly Infected with Clade C Human Immunodeficiency Virus Type 1

Jianming Tang,1 Shenghui Tang,1 Elena Lobashevsky,2 Angela D. Myracle,2 Ulgen Fideli,2 Grace Aldrovandi,3 Susan Allen,2 Rosemary Musonda,4 Richard A. Kaslow,1,2* and the Zambia-UAB HIV Research Project{dagger}

Departments of Medicine,1 Epidemiology and International Health,2 Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama 35294,3 Tropical Disease Research Center, Ndola, Zambia4

Received 4 February 2002/ Accepted 13 May 2002

The setpoint of viral RNA concentration (viral load [VL]) during chronic human immunodeficiency virus type 1 (HIV-1) infection reflects a virus-host equilibration closely related to CD8+ cytotoxic T-lymphocyte (CTL) responses, which rely heavily on antigen presentation by the human major histocompatibility complex (MHC) (i.e., HLA) class I molecules. Differences in HIV-1 VL among 259 mostly clade C virus-infected individuals (137 females and 122 males) in the Zambia-UAB HIV Research Project (ZUHRP) were associated with several HLA class I alleles and haplotypes. In particular, general linear model analyses revealed lower log10 VL among those with HLA allele B*57 (P = 0.002 [without correction]) previously implicated in favorable response and in those with HLA B*39 and A*30-Cw*03 (P = 0.002 to 0.016); the same analyses also demonstrated higher log10 VL among individuals with A*02-Cw*16, A*23-B*14, and A*23-Cw*07 (P = 0.010 to 0.033). These HLA effects remained strong (P = 0.0002 to 0.075) after adjustment for age, gender, and duration of infection and persisted across three orders of VL categories (P = 0.001 to 0.084). In contrast, neither B*35 (n = 15) nor B*53 (n = 53) showed a clear disadvantage such as that reported elsewhere for these closely related alleles. Other HLA associations with unusually high (A*68, B*41, B*45, and Cw*16) or low (B*13, Cw*12, and Cw*18) VL were either unstable or reflected their tight linkage respecting disequilibria with other class I variants. The three consistently favorable HLA class I variants retained in multivariable models and in alternative analyses were present in 30.9% of subjects with the lowest (<10,000 copies per ml) and 3.1% of those with the highest (>100,000) VL. Clear differential distribution of HLA profiles according to level of viremia suggests important host genetic contribution to the pattern of immune control and escape during HIV-1 infection.

* Corresponding author. Mailing address: Department of Epidemiology and International Health, University of Alabama at Birmingham, 220A Ryals Bldg., 1665 University Blvd., Birmingham, AL 35294. Phone: (205) 975-8698. Fax: (205) 934-8665. E-mail: rkaslow{at}uab.edu.

{dagger} Investigators on the Zambia-UAB HIV Research Project who contributed to this study were as follows: for Epidemiology and Clinical Studies, Susan Allen, University of Alabama at Birmingham (UAB), and Isaac Zulu, Elwyn Chomba, and Alan Haworth, University of Zambia School of Medicine (UZSM); for Virology, Beatrice Hahn, Feng Gao, Ulgen Fideli, and Grace Aldrovandi, UAB, Francis Kasolo, UZSM, and Eric Hunter, UAB; for Immunology, Steffanie Sabbaj and Mark Mulligan, UAB, and Bruce Walker, Marylyn Addo, and Marcus Altfelt, Harvard University; and for Immunogenetics, Jianming (James) Tang and Richard A. Kaslow, UAB.

Journal of Virology, August 2002, p. 8276-8284, Vol. 76, No. 16
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.16.8276-8284.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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