Department of Medicine.
J Infect Dis. 2014 Jan 1;209(1):66-73. doi: 10.1093/infdis/jit425. Epub 2013 Aug 6.
Determinants of intersubtype differences in human immunodeficiency virus type 1 (HIV-1) clinical disease progression remain unknown.
HIV-1 subtype was independently determined for 5 separate genomic regions in 396 HIV-1 seroconverters from Rakai, Uganda, using a multiregion hybridization assay. Replication capacities (RC) in samples from a subset of 145 of these subjects were determined. HIV-1 genomic regions and pol RC were examined for association with disease progression. Amino acid polymorphisms were examined for association with pol RC.
In multivariate analyses, the hazard for progression to the composite end point (defined as a CD4(+) T-cell count <250 cells/mm(3), antiretroviral therapy initiation, or death) among patients with subtype D pol infection was 2.4 times the hazard for those infected with subtype A pol infection (P = .001). Compared with subtype A pol (the reference group), the hazard for progression to the composite end point for subtype D pol infection with a pol RC >67% (ie, the median pol RC) was significantly greater (HR, 4.6; 95% confidence interval [CI], 1.9-11.0; P = .001), whereas the hazard for progression to the composite end point for subtype D pol infection with a pol RC ≤67% was not significantly different (HR, 2.2; 95% CI, 1.0-4.9; P = .051). Amino acid substitutions at protease positions 62 and 64 and at reverse transcriptase position 272 were associated with significant differences in pol RC.
HIV-1 pol gene intersubtype and RC differences are associated with disease progression and may be influenced by amino acid polymorphisms.
人类免疫缺陷病毒 1 型（HIV-1）临床疾病进展的亚型间差异的决定因素尚不清楚。
使用多重区域杂交测定法，在来自乌干达 Rakai 的 396 名 HIV-1 血清转换者的 5 个独立的 HIV-1 亚型基因组区域中独立确定 HIV-1 亚型。在其中 145 名受试者的样本中测定了复制能力（RC）。检查 HIV-1 基因组区域和 pol RC 与疾病进展的关联。检查氨基酸多态性与 pol RC 的关联。
在多变量分析中，D 型 pol 感染患者进展为复合终点（定义为 CD4(+)T 细胞计数<250 个/毫米 3、开始抗逆转录病毒治疗或死亡）的风险是 A 型 pol 感染患者的 2.4 倍（P =.001）。与 A 型 pol（参照组）相比，pol RC >67%（即 pol RC 的中位数）的 D 型 pol 感染患者进展为复合终点的风险显著更高（HR，4.6；95%置信区间[CI]，1.9-11.0；P =.001），而 pol RC ≤67%的 D 型 pol 感染患者进展为复合终点的风险无显著差异（HR，2.2；95%CI，1.0-4.9；P =.051）。蛋白酶位置 62 和 64 以及逆转录酶位置 272 的氨基酸取代与 pol RC 显著差异相关。
HIV-1 pol 基因亚型间和 RC 差异与疾病进展相关，并且可能受氨基酸多态性影响。
