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Session 61
Poster Abstracts Pathogenesis: Host Genetic Studies Thursday, 1:30 - 3:30 pm Hall D |
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/
Keywords: HLA; Supertype; African
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