Human leukocyte antigen genotype and risk of HIV disease progression before and after initiation of antiretroviral therapy

Mark H. Kuniholm, Xiaojiang Gao, Xiaonan Xue, Andrea Kovacs, Kathryn Anastos, Darlene Marti, Ruth M. Greenblatt, Mardge H. Cohen, Howard Minkoff, Stephen J. Gange, Melissa Fazzari, Mary A. Young, Howard D. Strickler, Mary Carrington

Research output: Contribution to journalArticle

17 Citations (Scopus)

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, HLAB*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.

Original languageEnglish (US)
Pages (from-to)10826-10833
Number of pages8
JournalJournal of Virology
Volume85
Issue number20
DOIs
StatePublished - Oct 2011

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HLA Antigens
disease course
Disease Progression
Genotype
HIV
Highly Active Antiretroviral Therapy
therapeutics
confidence interval
genotype
Confidence Intervals
odds ratio
Odds Ratio
Therapeutics
viral load
HLA antigens
Viral Load
genotyping
Multivariate Analysis
immune response

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Human leukocyte antigen genotype and risk of HIV disease progression before and after initiation of antiretroviral therapy. / Kuniholm, Mark H.; Gao, Xiaojiang; Xue, Xiaonan; Kovacs, Andrea; Anastos, Kathryn; Marti, Darlene; Greenblatt, Ruth M.; Cohen, Mardge H.; Minkoff, Howard; Gange, Stephen J.; Fazzari, Melissa; Young, Mary A.; Strickler, Howard D.; Carrington, Mary.

In: Journal of Virology, Vol. 85, No. 20, 10.2011, p. 10826-10833.

Research output: Contribution to journalArticle

Kuniholm, MH, Gao, X, Xue, X, Kovacs, A, Anastos, K, Marti, D, Greenblatt, RM, Cohen, MH, Minkoff, H, Gange, SJ, Fazzari, M, Young, MA, Strickler, HD & Carrington, M 2011, 'Human leukocyte antigen genotype and risk of HIV disease progression before and after initiation of antiretroviral therapy', Journal of Virology, vol. 85, no. 20, pp. 10826-10833. https://doi.org/10.1128/JVI.00804-11
Kuniholm, Mark H. ; Gao, Xiaojiang ; Xue, Xiaonan ; Kovacs, Andrea ; Anastos, Kathryn ; Marti, Darlene ; Greenblatt, Ruth M. ; Cohen, Mardge H. ; Minkoff, Howard ; Gange, Stephen J. ; Fazzari, Melissa ; Young, Mary A. ; Strickler, Howard D. ; Carrington, Mary. / Human leukocyte antigen genotype and risk of HIV disease progression before and after initiation of antiretroviral therapy. In: Journal of Virology. 2011 ; Vol. 85, No. 20. pp. 10826-10833.
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