Human Leukocyte Antigen (HLA) Genotype and Risk of HIV Disease

3 While HLA genotype has been associated with the rate of HIV disease progression in untreated patients, little is 4 known regarding these relationships in patients using highly active antiretroviral therapy (HAART). The limited 5 data reported to date identified few HLA–HIV disease associations in patients using HAART, and even 6 occasional associations opposite those found in untreated patients. We conducted high resolution HLA class I 7 and II genotyping in a random sample (N=860) of HIV-seropositive women enrolled in a long-term cohort 8 initiated in 1994. HLA-HIV disease associations before and after initiation of HAART were examined using 9 multivariate analyses. In untreated HIV-seropositive patients we observed many of the predicted associations, 10 consistent with prior studies. For example, HLA-B*57 (β =-0.7, 95% CI =-0.9–-0.5; P=5 x10 -11 ) and Bw4 (β=11 0.2 (-0.4–-0.1; P=0.009) were inversely associated with baseline HIV viral load, and B*57 was associated with 12 low risk of rapid CD4+ decline (OR=0.2, 95% CI=0.1-0.6; P=0.002). Conversely, in treated patients, the odds 13 of a virological response to HAART were lower for B*57:01 (OR=0.2; 95% CI: 0.0-0.9; P=0.03) and Bw4 14 (OR=0.4; 95% CI: 0.1-1.0; P=0.04) was associated with low odds of an immunological response. The 15 associations of HLA genotype with HIV disease are different and sometimes even opposite in treated and 16 untreated patients. 17

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