title: Human leukocyte antigen genotype and risk of HIV disease progression before and after initiation of antiretroviral therapy.
abstract: While the human leukocyte antigen (HLA) genotype has been associated with the rate of HIV disease progression in untreated patients, little is known regarding these relationships in patients using highly active antiretroviral therapy (HAART). The limited data reported to date identified few HLA-HIV disease associations in patients using HAART and even occasional associations that were opposite of those found in untreated patients. We conducted high-resolution HLA class I and II genotyping in a random sample (n = 860) of HIV-seropositive women enrolled in a long-term cohort initiated in 1994. HLA-HIV disease associations before and after initiation of HAART were examined using multivariate analyses. In untreated HIV-seropositive patients, we observed many of the predicted associations, consistent with prior studies. For example, HLA-B*57 (β = -0.7; 95% confidence interval [CI] = -0.9 to -0.5; P = 5 × 10⁻¹¹) and Bw4 (β = -0.2; 95% CI = -0.4 to -0.1; P = 0.009) were inversely associated with baseline HIV viral load, and B*57 was associated with a low risk of rapid CD4+ decline (odds ratio [OR] = 0.2; 95% CI = 0.1 to 0.6; P = 0.002). Conversely, in treated patients, the odds of a virological response to HAART were lower for B*57:01 (OR = 0.2; 95% CI = 0.0 to 0.9; P = 0.03), and Bw4 (OR = 0.4; 95% CI = 0.1 to 1.0; P = 0.04) was associated with low odds of an immunological response. The associations of HLA genotype with HIV disease are different and sometimes even opposite in treated and untreated patients.
authors.affiliation: Department of Epidemiology & Population Health, Albert Einstein College of Medicine, Belfer Building, Room 1308, 1300 Morris Park Ave., Bronx, NY 10461, USA. mark.kuniholm@einstein.yu.edu
authors.forename: Mark H
authors.initials: MH
authors.lastname: Kuniholm
authors.forename: Xiaojiang
authors.initials: X
authors.lastname: Gao
authors.forename: Xiaonan
authors.initials: X
authors.lastname: Xue
authors.forename: Andrea
authors.initials: A
authors.lastname: Kovacs
authors.forename: Kathryn
authors.initials: K
authors.lastname: Anastos
authors.forename: Darlene
authors.initials: D
authors.lastname: Marti
authors.forename: Ruth M
authors.initials: RM
authors.lastname: Greenblatt
authors.forename: Mardge H
authors.initials: MH
authors.lastname: Cohen
authors.forename: Howard
authors.initials: H
authors.lastname: Minkoff
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Gange
authors.forename: Melissa
authors.initials: M
authors.lastname: Fazzari
authors.forename: Mary A
authors.initials: MA
authors.lastname: Young
authors.forename: Howard D
authors.initials: HD
authors.lastname: Strickler
authors.forename: Mary
authors.initials: M
authors.lastname: Carrington
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D018450:Disease Progression; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000235:genetics*; D006680:HLA Antigens / Q000235:genetics*; D006801:Humans; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D006680:HLA Antigens