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Human Leukocyte Antigen Genotype and Risk of HIV Disease Progression before and after Initiation of Antiretroviral Therapy

  1. Author:
    Kuniholm, M. H.
    Gao, X. J.
    Xue, X. N.
    Kovacs, A.
    Anastos, K.
    Marti, D.
    Greenblatt, R. M.
    Cohen, M. H.
    Minkoff, H.
    Gange, S. J.
    Fazzari, M.
    Young, M. A.
    Strickler, H. D.
    Carrington, M.
  2. Author Address

    [Kuniholm, MH; Xue, XN; Anastos, K; Fazzari, M; Strickler, HD] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10461 USA. [Gao, XJ; Marti, D; Carrington, M] SAIC Frederick Inc, NCI Frederick, Canc & Inflammat Program, Expt Immunol Lab, Frederick, MD USA. [Gao, XJ; Marti, D; Carrington, M] Ragon Inst MGH MIT & Harvard, Charlestown, MA USA. [Kovacs, A] Univ So Calif, Dept Pediat, Los Angeles, CA 90089 USA. [Anastos, K] Montefiore Med Ctr, Dept Med, Bronx, NY 10467 USA. [Greenblatt, RM] Univ Calif San Francisco, Dept Clin Pharm, San Francisco, CA 94143 USA. [Cohen, MH] CORE Ctr, Cook Cty Bur Hlth Serv, Chicago, IL USA. [Minkoff, H] Maimonides Hosp, Dept Obstet & Gynecol, Brooklyn, NY 11219 USA. [Gange, SJ] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Young, MA] Georgetown Univ, Med Ctr, Dept Med, Washington, DC 20007 USA.;Kuniholm, MH (reprint author), Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Belfer Bldg,Room 1308,1300 Morris Pk Ave, Bronx, NY 10461 USA;mark.kuniholm@einstein.yu.edu
    1. Year: 2011
    2. Date: Oct
  1. Journal: Journal of Virology
    1. 85
    2. 20
    3. Pages: 10826-10833
  2. Type of Article: Article
  3. ISSN: 0022-538X
  1. 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 (beta = -0.7; 95% confidence interval [CI] = -0.9 to -0.5; P = 5 x 10(-11)) and Bw4 (beta = -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.

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External Sources

  1. DOI: 10.1128/jvi.00804-11
  2. WOS: 000296254100038

Library Notes

  1. Fiscal Year: FY2011-2012
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