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Session 61 Poster Abstracts
Pathogenesis: Host Genetic Studies
Thursday, 1:30 - 3:30 pm
Hall D


296    
Differential Effects of Individual B58 Supertype Alleles on Control of HIV-1 Disease in Native Africans
Aleksandr Lazaryan*1, E Lobashevsky1, J Mulenga2, E Karita3, S Allen4, J Tang1, and R Kaslow1
1Univ of Alabama at Birmingham, USA; 2Natl Blood Transfusion Svc, Lusaka, Zambia; 3Project San Francisco, Kigali, Rwanda; and 4Emory Univ, Atlanta, GA, USA

Background:  Within the B58 supertype (B58s), HLA-B*57 has been consistently associated with favorable outcomes during HIV-1 infection. This study further explored the association of each separate allelic member of the B58s with HIV-1 viral load or disease progression in native Africans.

Methods:  In untreated HIV-1-seropositive Zambians (n = 367) and Rwandans (n = 202), we used molecular HLA typing to define alleles in the B58s. Allelic associations with viral load in Zambians were assessed by multivariable methods for continuous data; allele distributions across 3 groups of Rwandans with increasing rates of HIV-1 disease progression (slow, intermediate, rapid) were analyzed by categorical data methods

Results:  In 109 Zambians and 73 Rwandans with B58s, no clear association with viral load or disease progression was observed. In a multivariable linear model controlling for age, gender and other established favorable and unfavorable HLA markers in Zambians, mean log10 viral load was lower in B*5703-positives (n = 35) [β estimate ± SE equal to ­0.34 ± 0.14 (p = 0.017)]. B*5801 carriers (n = 34) demonstrated a similar although non-significant trend (­0.16 ± 0.14, p = 0.27). In contrast, subjects with B*5802 (n = 29) had significantly higher log10 viral load (+0.37 ± 0.15, p = 0.018). Small numbers of carriers of B*1516 or B*1517 (n = 11) also had slightly higher log10 viral load (+0.18 ± 0.24, p = 0.45). Findings in Rwandans paralleled those in Zambians:  B*57 (n = 28) and B*5802 (n = 28) were associated with slow (p = 0.06) and rapid (p = 0.003) HIV-1 disease progression, respectively, whereas the distributions of B*5801 (n = 14) and B63 (n = 8) alleles were not appreciably different across the 3 disease progression groups (p > 0.4).

Conclusions:  In Zambians with subtype C and Rwandans with subtype A HIV-1 infection, individual B58s alleles, rather than the supertype as a whole, showed strikingly different associations with the available outcome measures. These findings caution against treating the B58s as a homogeneous designation in the context of HIV/AIDS in every population.

Keywords: HLA; Supertype; African