Infectious Diseases Department, Hospital Universitario Ramón y Cajal and Instituto de Investigación Sanitaria (IRYCIS), Madrid, Spain.
J Antimicrob Chemother. 2012 Feb;67(2):312-21. doi: 10.1093/jac/dkr478. Epub 2011 Nov 29.
Initiation of highly active antiretroviral therapy (HAART) with low CD4 lymphocyte counts is associated with AIDS-related and non-AIDS-related events and increased mortality. However, no clear association has been found with an increased rate of treatment failure.
We conducted a meta-analysis including randomized clinical trials of currently recommended HAART in naive patients to evaluate treatment response in very late starters (VLSs). Studies with information on response in at least one of the two strata (≤ 50 versus >50 CD4 cells/mm(3) and/or ≤ 200 versus >200 CD4 cells/mm(3)) and follow-up of at least 48 weeks were analysed. A pooled odds ratio of the effect of starting HAART with ≤ 50 versus >50 or ≤ 200 versus >200 CD4 cells/mm(3) for each arm by fitting a random-effect logistic regression model was computed. Sources of heterogeneity [sex, age, year of study initiation, nucleos(-t)ide pair and third drug] were investigated.
We included 25 treatment arms from 13 randomized clinical trials. Being a VLS consistently impairs treatment outcomes at 48 and 96 weeks. Only hepatitis C virus (HCV)/hepatitis B virus (HBV) coinfection was associated with a reduced impact of late initiation of HAART; at 48 weeks for 50 and 200 cells/mm(3) thresholds (P = 0.013 and P = 0.032, respectively). None of the remaining sources of heterogeneity explored was significantly associated with the impact of being a VLS.
We found that initiation of antiretroviral therapy with very low CD4 lymphocyte counts is consistently associated with poorer outcomes of HAART. This effect could be modulated by HBV/HCV coinfection, but not by the individual components of the HAART regimen.
在 CD4 淋巴细胞计数较低时启动高效抗逆转录病毒治疗(HAART)与艾滋病相关和非艾滋病相关事件以及死亡率增加有关。然而,尚未发现与治疗失败率增加有明确关联。
我们进行了一项荟萃分析,纳入了目前推荐的针对初治患者的 HAART 随机临床试验,以评估非常晚期开始治疗(VLS)的治疗反应。分析了至少有一个分层(≤50 与>50 CD4 细胞/mm(3)和/或≤200 与>200 CD4 细胞/mm(3))有反应信息且随访至少 48 周的研究。通过拟合随机效应逻辑回归模型计算每个手臂开始 HAART 时≤50 与>50 或≤200 与>200 CD4 细胞/mm(3)的治疗效果的合并优势比。研究了异质性来源(性别、年龄、研究启动年份、核苷(酸)类似物和第三药物)。
我们纳入了来自 13 项随机临床试验的 25 个治疗组。作为 VLS 始终会在 48 周和 96 周影响治疗结果。只有丙型肝炎病毒(HCV)/乙型肝炎病毒(HBV)合并感染与 HAART 晚期启动的影响降低相关;在 50 和 200 个细胞/mm(3)的阈值时(P=0.013 和 P=0.032)。未发现探索的其余异质性来源与作为 VLS 的影响有显著关联。
我们发现,以非常低的 CD4 淋巴细胞计数启动抗逆转录病毒治疗与 HAART 的结果较差始终相关。这种影响可能由 HBV/HCV 合并感染调节,但不受 HAART 方案的个体成分调节。