Table_1_HIV-1 tropism in low-level viral load HIV-1 infections during HAART in Guangdong, China.xlsx

BackgroundSince only a few studies have been conducted on the factors associated with different HIV-1 tropisms in low-level viral load HIV-1 infections in China, we investigated the sequences of HIV-1 V3 loop in prevalent HIV-1 subtypes and factors related to HIV-1 tropism and immune recovery in HIV-1 infections after 6 months of highly active antiretroviral therapy (HAART) in Guangdong, China.
MethodsPlasma samples with HIV-1 RNA of 400–999 copies/mL were collected. We analyzed the amino acid sequence of the V3 loop by in silico prediction algorithms. Mann–Whitney and Chi-square tests were used for statistical comparison. Furthermore, logistic regression and multiple linear regression were used, respectively, for factors associated with 351 HIV-1 tropism and immune recovery of 67 cases with continued CD4+ T cell count during HAART.
ResultsThere was a lower percentage of HIV-1 R5-tropic virus in CRF01_AE (66.3%) (p < 0.0001) and CRF55_01B (52.6%) (p < 0.0001) compared with both CRF07_BC (96.1%) and CRF08_BC (97.4%), respectively. Compared with the R5-tropic virus, higher proportions of IIe8/Val8, Arg11/Lys11, and Arg18/His18/Lys18 were observed in the X4-tropic virus of CRF01_AE and CRF07_BC (p < 0.0001). The baseline CD4+ T cell count (p < 0.0001) and baseline CD4+ T/CD8+ T ratio (p = 0.0006) of all R5-tropic infections were higher than those in the X4-tropic infection. The baseline CD4+ T cell count (odds ratio [OR] 0.9963, p = 0.0097), CRF07_BC (OR 0.1283, p = 0.0002), and CRF08_BC (OR 0.1124, p = 0.0381) were associated with less HIV-1 X4-tropism. The baseline CD4+ T cell count was a positive factor (p < 0.0001) in the recovery of CD4+ T cell count during HAART.
ConclusionR5-tropism represented the majority in low-level viral load HIV-1 infections receiving HAART for more than 6 months in Guangdong, China. The baseline immune level in the HIV-1 R5-tropic infections was higher than that in the X4-tropic infections. The amino acids of the 8th, 11th, and 18th of the HIV-1 V3 loop were more variable in the X4-tropic HIV-1. CRF01_AE, CRF55_01B, and lower baseline CD4+ T cell count were associated with more HIV-1 X4-tropism. The immune recovery during HAART was positively related to baseline CD4+ T cell count.

研究背景：鉴于目前中国针对低病毒载量HIV-1感染中与不同HIV-1嗜性相关的影响因素的研究较为匮乏，本研究针对中国广东省接受高效抗反转录病毒治疗（highly active antiretroviral therapy, HAART）满6个月的HIV-1感染者，对其流行的HIV-1亚型的V3环序列、与HIV-1嗜性及免疫重建相关的影响因素展开调查。
研究方法：收集HIV-1 RNA载量为400~999 copies/mL的血浆样本。通过计算机模拟（in silico）预测算法分析V3环的氨基酸序列。采用曼-惠特尼U检验（Mann–Whitney test）与卡方检验（Chi-square test）开展统计学比较。此外，分别采用logistic回归与多重线性回归，分析67例HAART治疗期间CD4+T细胞计数持续稳定的感染者中，与351株HIV-1嗜性及免疫重建相关的影响因素。
研究结果：与CRF07_BC（96.1%）及CRF08_BC（97.4%）相比，CRF01_AE（66.3%）与CRF55_01B（52.6%）毒株中HIV-1 R5嗜性病毒的占比更低（均p<0.0001）。相较于R5嗜性病毒，CRF01_AE与CRF07_BC的X4嗜性病毒中，第8位异亮氨酸/缬氨酸、第11位精氨酸/赖氨酸及第18位精氨酸/组氨酸/赖氨酸的占比更高（p<0.0001）。所有R5嗜性感染者的基线CD4+T细胞计数（p<0.0001）与基线CD4+/CD8+T细胞比值（p=0.0006）均高于X4嗜性感染者。基线CD4+T细胞计数（优势比[OR]=0.9963，p=0.0097）、CRF07_BC（OR=0.1283，p=0.0002）及CRF08_BC（OR=0.1124，p=0.0381）与更低的HIV-1 X4嗜性发生风险相关。基线CD4+T细胞计数是HAART治疗期间CD4+T细胞计数恢复的正向影响因素（p<0.0001）。
研究结论：在中国广东省接受超过6个月HAART治疗的低病毒载量HIV-1感染者中，R5嗜性病毒为主要流行株。HIV-1 R5嗜性感染者的基线免疫水平高于X4嗜性感染者。HIV-1 V3环第8、11、18位氨基酸在X4嗜性HIV-1中变异度更高。CRF01_AE、CRF55_01B亚型及较低的基线CD4+T细胞计数与更高的HIV-1 X4嗜性发生风险相关。HAART治疗期间的免疫重建与基线CD4+T细胞计数呈正相关。