Ford Deborah, Robins James M, Petersen Maya L, Gibb Diana M, Gilks Charles F, Mugyenyi Peter, Grosskurth Heiner, Hakim James, Katabira Elly, Babiker Abdel G, Walker A Sarah
Am J Epidemiol. 2015 Oct 1;182(7):633-43. doi: 10.1093/aje/kwv083. Epub 2015 Aug 26.
In Africa, antiretroviral therapy (ART) is delivered with limited laboratory monitoring, often none. In 2003-2004, investigators in the Development of Antiretroviral Therapy in Africa (DART) Trial randomized persons initiating ART in Uganda and Zimbabwe to either laboratory and clinical monitoring (LCM) or clinically driven monitoring (CDM). CD4 cell counts were measured every 12 weeks in both groups but were only returned to treating clinicians for management in the LCM group. Follow-up continued through 2008. In observational analyses, dynamic marginal structural models on pooled randomized groups were used to estimate survival under different monitoring-frequency and clinical/immunological switching strategies. Assumptions included no direct effect of randomized group on mortality or confounders and no unmeasured confounders which influenced treatment switch and mortality or treatment switch and time-dependent covariates. After 48 weeks of first-line ART, 2,946 individuals contributed 11,351 person-years of follow-up, 625 switches, and 179 deaths. The estimated survival probability after a further 240 weeks for post-48-week switch at the first CD4 cell count less than 100 cells/mm(3) or non-Candida World Health Organization stage 4 event (with CD4 count <250) was 0.96 (95% confidence interval (CI): 0.94, 0.97) with 12-weekly CD4 testing, 0.96 (95% CI: 0.95, 0.97) with 24-weekly CD4 testing, 0.95 (95% CI: 0.93, 0.96) with a single CD4 test at 48 weeks (baseline), and 0.92 (95% CI: 0.91, 0.94) with no CD4 testing. Comparing randomized groups by 48-week CD4 count, the mortality risk associated with CDM versus LCM was greater in persons with CD4 counts of <100 (hazard ratio = 2.4, 95% CI: 1.3, 4.3) than in those with CD4 counts of ≥100 (hazard ratio = 1.1, 95% CI: 0.8, 1.7; interaction P = 0.04). These findings support a benefit from identifying patients immunologically failing first-line ART at 48 weeks.
在非洲，抗逆转录病毒疗法（ART）的实施缺乏充分的实验室监测，往往根本没有监测。在2003 - 2004年，非洲抗逆转录病毒疗法发展（DART）试验的研究人员将在乌干达和津巴布韦开始接受ART治疗的患者随机分为实验室和临床监测组（LCM）或临床驱动监测组（CDM）。两组均每12周测量一次CD4细胞计数，但仅将结果反馈给LCM组的主治医生用于治疗管理。随访持续到2008年。在观察性分析中，对合并的随机分组使用动态边际结构模型来估计不同监测频率以及临床/免疫指标转换策略下的生存率。假设包括随机分组对死亡率或混杂因素无直接影响，且不存在影响治疗转换、死亡率或治疗转换以及时间依赖性协变量的未测量混杂因素。在一线ART治疗48周后，2946名个体提供了11351人年的随访数据，发生了625次治疗转换，179人死亡。对于首次CD4细胞计数低于100个细胞/mm³或非念珠菌性世界卫生组织4期事件（CD4计数<250）后48周进行治疗转换的患者，在接下来240周的估计生存概率为：每12周检测一次CD4时为0.96（95%置信区间（CI）：0.94，0.97），每24周检测一次CD4时为0.96（95%CI：0.95，0.97），在48周（基线）时进行一次CD4检测时为0.95（95%CI：0.93，0.96），不进行CD4检测时为0.92（95%CI：0.91，0.94）。按48周时的CD4计数比较随机分组，CD4计数<100的患者中，与CDM组相比，LCM组的死亡风险更高（风险比 = 2.4，95%CI：1.3，4.3），而CD4计数≥100的患者中风险比为1.1（95%CI：0.8，1.7；交互作用P = 0.04）。这些发现支持在48周时识别一线ART免疫治疗失败患者的益处。
