Kesselring Anouk M, Wit Ferdinand W, Sabin Caroline A, Lundgren Jens D, Gill M John, Gatell Jose M, Rauch Andri, Montaner Julio S, de Wolf Frank, Reiss Peter, Mocroft Amanda
HIV Monitoring Foundation, The Netherlands.
AIDS. 2009 Aug 24;23(13):1689-99. doi: 10.1097/QAD.0b013e32832d3b54.
This collaboration of seven observational clinical cohorts investigated risk factors for treatment-limiting toxicities in both antiretroviral-naive and experienced patients starting nevirapine-based combination antiretroviral therapy (NVPc).
Patients starting NVPc after 1 January 1998 were included. CD4 cell count at starting NVPc was classified as high (>400/microl/>250/microl for men/women, respectively) or low. Cox models were used to investigate risk factors for discontinuations due to hypersensitivity reactions (HSR, n = 6547) and discontinuation of NVPc due to treatment-limiting toxicities and/or patient/physician choice (TOXPC, n = 10,186). Patients were classified according to prior antiretroviral treatment experience and CD4 cell count/viral load at start NVPc. Models were stratified by cohort and adjusted for age, sex, nadir CD4 cell count, calendar year of starting NVPc and mode of transmission.
Median time from starting NVPc to TOXPC and HSR were 162 days [interquartile range (IQR) 31-737] and 30 days (IQR 17-60), respectively. In adjusted Cox analyses, compared to naive patients with a low CD4 cell count, treatment-experienced patients with high CD4 cell count and viral load more than 400 had a significantly increased risk for HSR [hazard ratio 1.45, confidence interval (CI) 1.03-2.03] and TOXPC within 18 weeks (hazard ratio 1.34, CI 1.08-1.67). In contrast, treatment-experienced patients with high CD4 cell count and viral load less than 400 had no increased risk for HSR 1.10 (0.82-1.46) or TOXPC within 18 weeks (hazard ratio 0.94, CI 0.78-1.13).
Our results suggest it may be relatively well tolerated to initiate NVPc in antiretroviral-experienced patients with high CD4 cell counts provided there is no detectable viremia.
这项由七个观察性临床队列组成的合作研究，调查了初治和经治患者在开始基于奈韦拉平的联合抗逆转录病毒治疗（NVPc）时出现治疗受限毒性的危险因素。
纳入1998年1月1日后开始NVPc治疗的患者。开始NVPc治疗时的CD4细胞计数分为高（男性>400/μl/女性>250/μl）或低。采用Cox模型研究因超敏反应（HSR，n = 6547）导致停药以及因治疗受限毒性和/或患者/医生选择导致停用NVPc（TOXPC，n = 10,186）的危险因素。根据既往抗逆转录病毒治疗经验以及开始NVPc治疗时的CD4细胞计数/病毒载量对患者进行分类。模型按队列分层，并对年龄、性别、最低CD4细胞计数、开始NVPc治疗的日历年和传播方式进行了调整。
从开始NVPc治疗到出现TOXPC和HSR的中位时间分别为162天[四分位间距（IQR）31 - 737]和30天（IQR 17 - 60）。在调整后的Cox分析中，与CD4细胞计数低的初治患者相比，CD4细胞计数高且病毒载量超过400的经治患者发生HSR的风险显著增加[风险比1.45，置信区间（CI）1.03 - 2.03]，并且在18周内发生TOXPC的风险也显著增加（风险比1.34，CI 1.08 - 1.67）。相比之下，CD4细胞计数高且病毒载量低于400的经治患者发生HSR的风险未增加[1.10（0.82 - 1.46）]，在18周内发生TOXPC的风险也未增加（风险比0.94，CI 0.78 - 1.13）。
我们的结果表明，对于CD4细胞计数高且无可检测病毒血症的经治患者，开始使用NVPc可能耐受性相对较好。
