327-W. Human Major Histocompatibility Complex (HLA) Class I Variants in HIV-1-Infected Zambians and Their Relative Effect on Plasma Viral RNA Concentration in the Absence of Antiretroviral Therapy

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Session 51 Poster Session
Impact of Host Genetics on Viral Transmission and Disease Progression
Session Time: 4:30-6:30 pm
Room 4E-F

327-W.

Human Major Histocompatibility Complex (HLA) Class I Variants in HIV-1-Infected Zambians and Their Relative Effect on Plasma Viral RNA Concentration in the Absence of Antiretroviral Therapy
J. Tang*¹, S. Tang¹, U. Fideli¹, R. Musonda², E. Lobashevsky¹, S. Allen¹, G. Aldrovandi¹, and R. A. Kaslow¹
¹Univ. of Alabama, Birmingham and ²Tropical Disease Res. Ctr., Ndola, Zambia

Background: Allelic forms of human major histocompatibility complex (HLA) class I molecules differentially present endogenous antigens to CD8+ cytotoxic T-lymphocytes (CTLs) for immune surveillance. The impact of HLA alleles on HIV-1 disease progression has often differed in the magnitude and consistency across cohorts, ethnicity, and various stages of infection. We examined the relative contribution of HLA class I alleles to the variability in HIV viral load (VL) among relatively healthy seroconverted and seroprevalent participants in the Zambia-UAB HIV Research Project.
Methods: HLA class I alleles in 259 HIV-1 clade C virus-infected Zambians (137 females and 122 males) were resolved by molecular techniques including PCR with sequence-specific primers, reference-strand conformation analysis, and DNA sequencing. The distributions of major HLA alleles and haplotypes (carrier frequency > 2%) were compared among participants categorized according to their plasma HIV-1 RNA concentration, which predicts both disease progression and sexual transmission. The relative HLA effects on mean log₁₀VL were assessed by multivariable analytic techniques.
Results: HIV VL was lower in HLA B*39, B*5703, and A*30-Cw*03 carriers (p=0.001-0.003) and higher in those carrying B*18, B*41, B*45, and A*23-B*14 (p=0.01-0.09). These effects persisted with adjustment for age, gender, and duration of infection. In contrast, neither B*35 (n=15) nor B*53 (n=53) showed any of the disadvantage reported elsewhere for those alleles. Associations of additional alleles (A*68, Cw*12, Cw*16, and Cw*18) with unusually high or low VL (p=0.0003-0.04) were largely due to their tight linkage disequilibria with HLA-B variants. Overall, the favorable HLA class I variants were found in 35% of subjects with VL <10,000 and 3% of those with VL >100,000.
Conclusions: HLA class I alleles and haplotypes that influence HIV-1 VL in clade C virus-infected Zambians appeared rather dissimilar to those seen earlier in clade B virus-infected Caucasians. In successive generations of clade C HIV-1-infected populations, diminished frequency of unfavorable and concomitant accumulation of favorable antigen presenting molecules can alter the genetic composition of HIV/AIDS vaccine target groups.

Š2002 9^th Conference on Retroviruses and Opportunistic Infections