From the *University of California, San Diego; †Rady Children's Hospital, San Diego, CA; and ‡Center for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, MA.
Pediatr Infect Dis J. 2013 Nov;32(11):1230-6. doi: 10.1097/INF.0b013e31829e4d06.
Vitamin D deficiency is common in HIV infection and has been associated with advanced disease. This study investigated whether vitamin D-related genetic variants were associated with disease progression in HIV-infected children.
The Fok-I (C/T), Bsm-I (G/A), GC (A/C), DHCR7 (G/T) and CYP2R1 (G/A) genetic variants were detected by real-time polymerase chain reaction in HIV-infected children who participated in the Pediatric AIDS Clinical Trials Group P152 and P300 protocols, which predated the availability of effective combination antiretroviral therapy. The primary endpoints included time to progression to the first HIV-related disease endpoint (≥2 opportunistic infection, weight growth failure) or death, which constituted the progression-free survival. Analyses were performed for age>2 years and ≤2 years separately adjusting for race and treatment effect.
Of the 998 children evaluated, 139 experienced HIV disease progression. For children>2 years, rapid disease progression was associated with the DHCR7 G allele compared with the T allele (G/G vs. T/T: hazard ratio [HR]=5.0, P = 0.035; G/T vs. T/T: HR=4.5, P=0.042; G/G+G/T vs. T/T: HR=4.8, P=0.036) and the Bsm-I A allele compared with the G allele (A/G vs. G/G: HR=2.2, P=0.014 and A/G+A/A vs. G/G: HR=2.0, P=0.026). In children≤2 years, the Bsm-I A allele increased the risk of disease progression in Hispanics (A/A vs. G/A+G/G: HR=2.8, P=0.03 and A/A vs. G/G: HR=2.8, P=0.046) and whites (A/A vs. G/G: HR=6.6, P=0.025 and A/A vs. G/A+G/G: HR=3.6, P=0.038).
Vitamin D-related host genetic variants that alter the availability and activity of vitamin D are associated with risk of HIV disease progression in children and may vary by age and race.
维生素 D 缺乏在 HIV 感染中很常见，并且与疾病的进展有关。本研究旨在调查维生素 D 相关的遗传变异是否与 HIV 感染儿童的疾病进展有关。
采用实时聚合酶链反应检测了参与儿科艾滋病临床试验组 P152 和 P300 方案的 HIV 感染儿童的 Fok-I（C/T）、Bsm-I（G/A）、GC（A/C）、DHCR7（G/T）和 CYP2R1（G/A）基因变异。这些儿童在有效联合抗逆转录病毒治疗之前就参与了这些方案。主要终点包括进展为首次与 HIV 相关的疾病终点（≥2 种机会性感染、体重增长失败）或死亡的时间，这构成了无进展生存。分析分别针对年龄>2 岁和≤2 岁的儿童进行，同时调整了种族和治疗效果。
在 998 名接受评估的儿童中，有 139 名发生了 HIV 疾病进展。对于年龄>2 岁的儿童，与 T 等位基因相比，DHCR7 G 等位基因与快速疾病进展相关（G/G 与 T/T：风险比[HR]=5.0，P=0.035；G/T 与 T/T：HR=4.5，P=0.042；G/G+G/T 与 T/T：HR=4.8，P=0.036），与 Bsm-I A 等位基因相比，G 等位基因与快速疾病进展相关（A/G 与 G/G：HR=2.2，P=0.014；A/G+A/A 与 G/G：HR=2.0，P=0.026）。对于年龄≤2 岁的儿童，Bsm-I A 等位基因增加了西班牙裔（A/A 与 G/A+G/G：HR=2.8，P=0.03；A/A 与 G/G：HR=2.8，P=0.046）和白人（A/A 与 G/G：HR=6.6，P=0.025；A/A 与 G/A+G/G：HR=3.6，P=0.038）发生疾病进展的风险。
改变维生素 D 的可用性和活性的维生素 D 相关宿主遗传变异与儿童 HIV 疾病进展的风险相关，并且可能因年龄和种族而异。
