Daar E S, Lynn H, Donfield S, Gomperts E, Hilgartner M W, Hoots K, Chernoff D, Winkler C, O'Brien S J
Cedars-Sinai Burns & Allen Research Institute, Department of Medicine, and the University of California Los Angeles School of Medicine, 90048, USA.
J Acquir Immune Defic Syndr. 1999 Aug 1;21(4):317-25. doi: 10.1097/00126334-199908010-00010.
We have investigated the effects of plasma HIV RNA, CD4+ T lymphocytes and chemokine receptors CCR5 and CCR2b on HIV disease progression in hemophiliacs. We prospectively observed during follow-up 207 HIV-infected hemophiliacs in the Hemophilia Growth and Development Study. Plasma HIV RNA was measured on cryopreserved plasma from enrollment using the Chiron Corporation bDNA (version 2.0) assay. Genoytpe variants CCR2b-641 and CCR5-delta32 were detected using standard molecular techniques. Those with the mutant allele for CCR2b, and to a lesser extent CCR5, had lower plasma HIV RNA, and higher CD4+ T lymphocytes than did those without these genetic variants. After controlling for the effects of plasma HIV RNA and CD4+ T lymphocytes, those with the CCR2b mutant allele compared with those wild-type, had a trend toward a lower risk of progression to AIDS, adjusted relative hazard of 1.94 (95% confidence interval [CI], 0.9-4.18; p = .092), and AIDS-related death, relative hazard 1.97 (95% CI, 0.98-4.00; p = .059). We conclude that plasma HIV RNA, CD4+ T lymphocytes, and CCR genotypes are correlated, and the protective affect of CCR2b against HIV disease progression is not completely explained by plasma HIV RNA or CD4+ T-lymphocyte number.
我们研究了血浆HIV RNA、CD4+ T淋巴细胞以及趋化因子受体CCR5和CCR2b对血友病患者HIV疾病进展的影响。在血友病生长与发育研究中，我们对207例HIV感染的血友病患者进行了前瞻性随访观察。使用Chiron公司的bDNA（2.0版）检测法，对入组时冻存的血浆进行血浆HIV RNA检测。采用标准分子技术检测CCR2b - 641和CCR5 - delta32基因型变异。携带CCR2b突变等位基因的患者，以及携带CCR5突变等位基因程度较轻的患者，其血浆HIV RNA水平低于未携带这些基因变异的患者，CD4+ T淋巴细胞水平则高于后者。在控制了血浆HIV RNA和CD4+ T淋巴细胞的影响后，与野生型相比，携带CCR2b突变等位基因的患者向艾滋病进展的风险有降低趋势，调整后的相对风险为1.94（95%置信区间[CI]，0.9 - 4.18；p = 0.092），与艾滋病相关死亡的相对风险为1.97（95% CI，0.98 - 4.00；p = 0.059）。我们得出结论，血浆HIV RNA、CD4+ T淋巴细胞和CCR基因型相互关联，CCR2b对HIV疾病进展的保护作用不能完全由血浆HIV RNA或CD4+ T淋巴细胞数量来解释。
