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J Acquir Immune Defic Syndr. 2011 May 1;57(1):32-9. doi: 10.1097/QAI.0b013e3182119244.

HLA alleles are associated with altered risk for disease progression and central nervous system impairment of HIV-infected children.

Author information

1
Department of Pediatrics, Division of Infectious Diseases, University of California San Diego, La Jolla, CA 92093-0672, USA. kusingh@ucsd.edu

Abstract

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.

PMID:
21283014
PMCID:
PMC3107908
DOI:
10.1097/QAI.0b013e3182119244
[Indexed for MEDLINE]
Free PMC Article
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