San Raffaele Scientific Institute, Milan, Italy.
J Antimicrob Chemother. 2012 May;67(5):1224-7. doi: 10.1093/jac/dkr600. Epub 2012 Jan 31.
To investigate the value of tropism (determined by genotypic testing) to predict CD4 depletion in HIV-infected antiretroviral-naive patients with high CD4 counts.
Viral tropism was determined by geno2pheno (false positive rate = 10%) in 223 HIV-infected subjects naive to antiretrovirals with CD4 count ≥350 cells/μL and HIV-RNA >500 copies/mL enrolled in the ICONA Foundation Study for whom a stored plasma sample (baseline) was retrospectively tested. We monitored CD4 cell count and identified predictors of decline before antiretroviral therapy initiation, applying a mixed linear model with covariates (age, gender, tropism, HIV risk factor, calendar year of HIV infection, months from HIV diagnosis to baseline, hepatitis C virus status, CD4 and HIV-RNA at sample collection and duration of follow-up).
Two hundred and twenty-three subjects met the eligibility criteria; 137 (61%) were male and the median age was 35 (31-40) years. Median follow-up was 16.4 (3.2-37.2) months. Median CD4 decrease during follow-up was -157 (-278 to -13) cells/μL. At baseline, 192 (86%) subjects were defined as harbouring R5 virus and 31 (14%) non-R5. Median CD4 count was 571 (458-729) cells/μL and median HIV-RNA was 4.08 (3.57-4.55) log(10) copies/mL. At multivariable analysis, a greater mean CD4 decrease was associated with non-R5 viral tropism (-159.9 ± 12.22, P = 0.0002) at baseline. Other significant covariates were female gender, older age, intravenous drug use, longer duration of follow-up, and higher CD4 cell count and higher HIV-RNA at sample collection.
In patients with CD4 counts ≥350 cells/μL, non-R5 viral tropism by geno2pheno is predictive of CD4 decrease independent of their viral set point and CD4 counts.
通过基因分型检测来探究病毒嗜性（即病毒趋向性）对预测 HIV 感染且未接受过抗逆转录病毒治疗、初始 CD4 计数较高（≥350 个/μL）的患者中 CD4 细胞耗竭的价值。
在 ICONA 基金会研究中，对 223 名 HIV 感染且初治、初始 CD4 计数≥350 个/μL 且 HIV-RNA＞500 拷贝/mL 的患者进行基因 2 表型（假阳性率为 10%）检测，以确定病毒嗜性，这些患者有储存的血浆样本（基线）进行回顾性检测。我们监测 CD4 细胞计数，并应用包含协变量（年龄、性别、病毒嗜性、HIV 风险因素、HIV 感染的年份、从 HIV 诊断到基线的时间、丙型肝炎病毒状态、样本采集时的 CD4 和 HIV-RNA、随访时间）的混合线性模型，来确定抗逆转录病毒治疗开始前 CD4 细胞计数下降的预测因素。
223 名符合入选标准的患者中，137 名（61%）为男性，中位年龄为 35（31-40）岁。中位随访时间为 16.4（3.2-37.2）个月。中位随访期间 CD4 细胞下降值为-157（-278 至-13）个/μL。基线时，192 名（86%）患者被定义为携带 R5 病毒，31 名（14%）患者携带非 R5 病毒。中位 CD4 计数为 571（458-729）个/μL，中位 HIV-RNA 为 4.08（3.57-4.55）log10 拷贝/mL。多变量分析显示，基线时非 R5 病毒嗜性与平均 CD4 下降值较大相关（-159.9±12.22，P=0.0002）。其他显著的协变量包括女性、年龄较大、静脉吸毒、随访时间较长、样本采集时 CD4 计数较高和 HIV-RNA 较高。
在 CD4 计数≥350 个/μL 的患者中，基因 2 表型检测的非 R5 病毒嗜性可预测 CD4 下降，独立于病毒设定点和 CD4 计数。
