Wolbers Marcel, Battegay Manuel, Hirschel Bernard, Furrer Hansjakob, Cavassini Matthias, Hasse Barbara, Vernazza Pietro L, Bernasconi Enos, Kaufmann Gilbert, Bucher Heiner C
Basel Institute for Clinical Epidemiology, University Hospital Basel, Switzerland.
Antivir Ther. 2007;12(6):889-97.
CD4+ T-cell recovery in patients with continuous suppression of plasma HIV-1 viral load (VL) is highly variable. This study aimed to identify predictive factors for long-term CD4+ T-cell increase in treatment-naive patients starting combination antiretroviral therapy (cART).
Treatment-naive patients in the Swiss HIV Cohort Study reaching two VL measurements <50 copies/ml >3 months apart during the 1st year of cART were included (n=1816 patients). We studied CD4+ T-cell dynamics until the end of suppression or up to 5 years, subdivided into three periods: 1st year, years 2-3 and years 4-5 of suppression. Multiple median regression adjusted for repeated CD4+ T-cell measurements was used to study the dependence of CD4+ T-cell slopes on clinical covariates and drug classes.
Median CD4+ T-cell increases following VL suppression were 87, 52 and 19 cells/microl per year in the three periods. In the multiple regression model, median CD4+ T-cell increases over all three periods were significantly higher for female gender, lower age, higher VL at cART start, CD4+ T-cell <650 cells/microl at start of the period and low CD4+ T-cell increase in the previous period. Patients on tenofovir showed significantly lower CD4+ T-cell increases compared with stavudine.
In our observational study, long-term CD4+ T-cell increase in drug-naive patients with suppressed VL was higher in regimens without tenofovir. The clinical relevance of these findings must be confirmed in, ideally, clinical trials or large, collaborative cohort projects but could influence treatment of older patients and those starting cART at low CD4+ T-cell levels.
血浆HIV-1病毒载量(VL)持续受到抑制的患者,其CD4+ T细胞的恢复情况差异很大。本研究旨在确定初治患者开始联合抗逆转录病毒治疗(cART)后长期CD4+ T细胞增加的预测因素。
纳入瑞士HIV队列研究中的初治患者,这些患者在cART的第1年中,有两次VL测量值<50拷贝/ml且间隔超过3个月(n = 1816例患者)。我们研究了CD4+ T细胞动力学,直至抑制结束或长达5年,分为三个阶段:抑制的第1年、第2 - 3年和第4 - 5年。采用针对重复CD4+ T细胞测量进行调整的多元中位数回归,研究CD4+ T细胞斜率对临床协变量和药物类别之间的依赖性。
在这三个阶段中,VL抑制后CD4+ T细胞的中位数增加分别为每年87、52和19个细胞/微升。在多元回归模型中,在所有三个阶段,女性、年龄较小、cART开始时VL较高、阶段开始时CD4+ T细胞<650个细胞/微升以及上一阶段CD4+ T细胞增加较低的患者,其CD4+ T细胞中位数增加显著更高。与司他夫定相比,使用替诺福韦的患者CD4+ T细胞增加显著更低。
在我们的观察性研究中,未使用替诺福韦的方案中,病毒载量受到抑制的初治患者长期CD4+ T细胞增加更高。这些发现的临床相关性,理想情况下必须在临床试验或大型合作队列项目中得到证实,但可能会影响老年患者以及CD4+ T细胞水平较低时开始cART的患者的治疗。