Qin Min, Brummel Sean, Singh Kumud K, Fenton Terence, Spector Stephen A
From the *Center for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, MA; and †University of California, San Diego, La Jolla, CA and Rady Children's Hospital, San Diego, CA.
Pediatr Infect Dis J. 2014 Sep;33(9):946-52. doi: 10.1097/INF.0000000000000330.
CD4 T-lymphocyte (CD4) counts and HIV plasma RNA concentration (RNA) are 2 key HIV disease markers. The complex interplay between virus and host genetics may contribute to differences in viral set point and CD4 status. Determining the effects of host genetic variation on HIV disease markers is often complicated by the use of antiretroviral therapy. In this study, the association between genetic variants and baseline HIV RNA and CD4 counts was examined in a large cohort of antiretroviral naïve children.
Specimens from 1053 HIV-infected children were screened for single nucleotide polymorphisms in 78 regions from 17 genes. Linear regression with a robust variance estimator was used to test the association between genetic markers with HIV RNA and CD4 count, controlling for age, race/ethnicity and study. False discovery rate (FDR) controlling was used to adjust for multiple testing.
The study population was 60% black, 26% Hispanic and 13% white; median age 2.35 years; 55% female. Baseline median CD4 count was 780/mm; median log10 HIV RNA was 5.17 copies/mL. For analyses of the associations of genetic makers with baseline CD4 count, 6 HLA and 4 additional markers exhibited P < 0.05, but none met the criteria for statistical significance with FDR controlled at 0.05. For baseline HIV RNA, HLA DRB115, DRB110, B-27/57, B-14, Cw-8, B-57 were statistically significant with FDR controlled at 0.05.
These results provide strong evidence that HLA DRB115, DRB110, B-27/57, B-14, Cw-8, B-57 are associated with HIV RNA and play a role in HIV pathogenesis in infected children.
CD4 T淋巴细胞（CD4）计数和HIV血浆RNA浓度（RNA）是两个关键的HIV疾病标志物。病毒与宿主基因之间复杂的相互作用可能导致病毒载量设定点和CD4状态的差异。确定宿主基因变异对HIV疾病标志物的影响通常因抗逆转录病毒疗法的使用而变得复杂。在本研究中，在一大群未接受过抗逆转录病毒治疗的儿童中，研究了基因变异与基线HIV RNA及CD4计数之间的关联。
对1053名HIV感染儿童的样本进行筛查，以检测17个基因中78个区域的单核苷酸多态性。使用具有稳健方差估计器的线性回归来检验基因标志物与HIV RNA及CD4计数之间的关联，并对年龄、种族/民族和研究进行控制。采用错误发现率（FDR）控制方法对多重检验进行校正。
研究人群中60%为黑人，26%为西班牙裔，13%为白人；中位年龄2.35岁；55%为女性。基线CD4计数中位数为780/mm；HIV RNA对数中位数为5.17拷贝/mL。在分析基因标志物与基线CD4计数的关联时，6个HLA和另外4个标志物的P值<0.05，但在FDR控制为0.05时，均未达到统计学显著性标准。对于基线HIV RNA，在FDR控制为0.05时，HLA DRB115、DRB110、B-27/57、B-14、Cw-8、B-57具有统计学显著性。
这些结果提供了强有力证据，表明HLA DRB115、DRB110、B-27/57、B-14、Cw-8、B-57与HIV RNA相关，并在受感染儿童的HIV发病机制中起作用。
