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HLA Alleles are Associated With Altered Risk for Disease Progression and Central Nervous System Impairment of HIV-Infected Children

Singh, Kumud K PhD*; Gray, Ping Kathryn PhD†‡; Wang, Yan MS; Fenton, Terence EdD; Trout, Rodney N BS*; Spector, Stephen A MD

JAIDS Journal of Acquired Immune Deficiency Syndromes: May 1st, 2011 - Volume 57 - Issue 1 - p 32-39
doi: 10.1097/QAI.0b013e3182119244
Clinical Science

Objective: To examine the effects of human leukocyte antigen (HLA) alleles on HIV-1-related disease progression and central nervous system (CNS) impairment in children.

Design: Five hundred seventy-two HIV-1-infected children, identified as disease progressors or nonprogressors, were selected from PACTG P152 and P300 through a case-cohort sampling scheme. Study endpoints were HIV-1-related disease progression-free survival and time to CNS impairment.

Methods: DNA was genotyped for HLA alleles using a Luminex 100 platform. Weighted Kaplan-Meier methods, and Cox proportional hazards models were used to assess the effects of HLA alleles on study endpoints.

Results: Presence of the B-27 allele (n = 20) was associated with complete protection against disease progression and CNS impairment over the median follow-up of 26 months (P < 0.0001 for both). These findings held in multivariate analyses controlling for baseline covariates including race, gender, age, log HIV-1 RNA, CD4+ lymphocyte count and percent, weight for age z score and treatment, and for other genotypes shown to affect HIV-1-related disease progression. Also, although the Cw-2 allele protected against disease progression [Hazard ratio (HR), 0.48; 95% confidence interval (CI): 0.28 to 0.81; P = 0.006], the A-24 allele was associated with more rapid CNS impairment (HR: 2.01; 95% CI: 1.04 to 3.88; P = 0.04). The HLA class II DQB1-2 allele was associated with a delayed disease progression (HR: 0.66; 95% CI: 0.47-0.92; P = 0.01) and CNS impairment (HR: 0.58; 95% CI: 0.36 to 0.93; P = 0.02).

Conclusions: Presence of B-27, Cw-2, or DQB1-2 alleles was associated with delayed HIV-1 disease progression, while B-27, A-24, and DQB1-2 alleles were associated with altered progression to CNS impairment in children.

From the *Department of Pediatrics, Division of Infectious Diseases, University of California San Diego, La Jolla, CA; †Center for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, MA; ‡Department of Biostatistics and Computational Biology, Dana Farber Cancer Institute, Boston, MA; and §Department of Pediatrics, Division of Infectious Diseases, Rady Children's Hospital San Diego, San Diego, CA.

Received for publication October 16, 2010; accepted January 20, 2011.

Supported by grants from the National Institute of Allergy and Infectious Diseases, the International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) Network (AI-069536) and 5R01MH085608.

Presented in part at the XVI Conference on Retroviruses and Opportunistic Infections, February 8-11, 2009, Montreal, Canada (poster presentation no. 893).

Informed consent was obtained from study participants.

This study followed the human experimentation guidelines of the US Department of Health and Human Services and the UCSD review board.

Correspondence to: Stephen A. Spector, MD, Department of Pediatrics, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0672 (e-mail: saspector@ucsd.edu) or Kumud K. Singh, PhD, Department of Pediatrics, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0672 (e-mail: kusingh@ucsd.edu).

© 2011 Lippincott Williams & Wilkins, Inc.