Department of Pediatrics, Division of Infectious Diseases, University of California San Diego, La Jolla, CA 92093-0672, USA.
J Acquir Immune Defic Syndr. 2011 May 1;57(1):32-9. doi: 10.1097/QAI.0b013e3182119244.
To examine the effects of human leukocyte antigen (HLA) alleles on HIV-1-related disease progression and central nervous system (CNS) impairment in children.
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.
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.
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).
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.
探讨人类白细胞抗原（HLA）等位基因对 HIV-1 相关疾病进展和儿童中枢神经系统（CNS）损害的影响。
通过病例-队列抽样方案，从 PACTG P152 和 P300 中选择了 572 名 HIV-1 感染的儿童，将其确定为疾病进展者或非进展者。研究终点为 HIV-1 相关疾病无进展生存和发生 CNS 损害的时间。
使用 Luminex 100 平台对 HLA 等位基因进行基因分型。采用加权 Kaplan-Meier 方法和 Cox 比例风险模型评估 HLA 等位基因对研究终点的影响。
20 名 B-27 等位基因（n = 20）的存在与 26 个月的中位随访期间完全免受疾病进展和 CNS 损害有关（均 P < 0.0001）。在控制基线协变量（包括种族、性别、年龄、HIV-1 RNA 对数、CD4 淋巴细胞计数和百分比、体重年龄 z 评分和治疗以及其他已证明影响 HIV-1 相关疾病进展的基因型）的多变量分析中，这些发现仍然存在。此外，尽管 Cw-2 等位基因可预防疾病进展（风险比[HR]，0.48；95%置信区间[CI]：0.28 至 0.81；P = 0.006），但 A-24 等位基因与更快速的 CNS 损害相关（HR：2.01；95% CI：1.04 至 3.88；P = 0.04）。HLA Ⅱ类 DQB1-2 等位基因与疾病进展延迟相关（HR：0.66；95% CI：0.47 至 0.92；P = 0.01）和 CNS 损害（HR：0.58；95% CI：0.36 至 0.93；P = 0.02）。
B-27、Cw-2 或 DQB1-2 等位基因的存在与 HIV-1 疾病进展延迟相关，而 B-27、A-24 和 DQB1-2 等位基因与儿童中枢神经系统损害的进展改变相关。
