Golub Elizabeth T, Benning Lorie, Sharma Anjali, Gandhi Monica, Cohen Mardge H, Young Mary, Gange Stephen J
Johns Hopkins Bloomberg School of Public Health, Department of Epidemiology, Baltimore, Maryland 21205, USA.
Clin Infect Dis. 2008 Jan 15;46(2):305-12. doi: 10.1086/524752.
It is important to elucidate differences among initial highly active antiretroviral therapy (HAART) regimen types in comparative studies of therapy effectiveness. We aimed to identify predictors of initiation with different HAART regimen types and the effect of initial regimen type on switching and immunologic response to therapy--controlling for those predictors--among human immunodeficiency virus (HIV)-infected women in the United States.
Participants in the Women's Interagency HIV Study underwent semiannual interview, venipuncture, and clinical examination. Those beginning with protease inhibitor-based, nonnucleoside reverse-transcriptase inhibitor (NNRTI)-based, or triple-nucleoside reverse-transcriptase inhibitor (NRTI)-based HAART during April 1996-March 2005 were eligible for analysis. Predictors of initial regimen type were assessed with polytomous logistic regression. Correlates of switching were assessed with discrete-time proportional hazards models, and immunologic response to therapy was assessed with linear regression.
Among 1555 HAART initiators, CD4(+) lymphocyte count and HIV load were significant predictors of initial regimen type during 1996-2002; only sociodemographic predictors were significant during 2002-2005. Initial regimen type was not a significant predictor of subsequent regimen switching. Compared with those whose initial treatment was protease inhibitor-based HAART, those who began with triple-NRTI-based regimens had significantly lower CD4(+) cell counts at 1 year (P=.006) and 2 years (P=.004) after initiation; NNRTI initiators had lower CD4(+) cell counts after 2 years (P=.05).
We demonstrate that predictors of initial regimen type among women in the United States have been changing over time. Protease inhibitor initiators had significantly higher CD4(+) cell counts than did NNRTI or triple-NRTI initiators up to 2 years after HAART initiation. Adjustment for biological predictors of initial regimen is important to avoid confounding in the study of treatment effectiveness.
在治疗效果的比较研究中，阐明初始高效抗逆转录病毒治疗（HAART）方案类型之间的差异很重要。我们旨在确定美国感染人类免疫缺陷病毒（HIV）的女性中，不同HAART方案类型起始治疗的预测因素，以及初始方案类型对治疗转换和免疫反应的影响（在控制这些预测因素的情况下）。
女性机构间HIV研究的参与者每半年接受一次访谈、静脉穿刺和临床检查。在1996年4月至2005年3月期间开始接受基于蛋白酶抑制剂、基于非核苷类逆转录酶抑制剂（NNRTI）或基于三联核苷类逆转录酶抑制剂（NRTI）的HAART治疗的患者符合分析条件。使用多分类逻辑回归评估初始方案类型的预测因素。使用离散时间比例风险模型评估治疗转换的相关因素，并使用线性回归评估对治疗的免疫反应。
在1555名开始接受HAART治疗的患者中，CD4（+）淋巴细胞计数和HIV载量是1996 - 2002年期间初始方案类型的显著预测因素；在2002 - 2005年期间，只有社会人口统计学预测因素具有显著性。初始方案类型不是后续治疗方案转换的显著预测因素。与初始治疗为基于蛋白酶抑制剂的HAART的患者相比，开始接受基于三联NRTI方案治疗的患者在开始治疗后1年（P = 0.006）和2年（P = 0.004）时CD4（+）细胞计数显著更低；开始接受基于NNRTI方案治疗的患者在2年后CD4（+）细胞计数更低（P = 0.05）。
我们证明，美国女性中初始方案类型的预测因素随时间发生了变化。在HAART治疗开始后的2年内，开始接受蛋白酶抑制剂治疗的患者的CD4（+）细胞计数显著高于开始接受NNRTI或三联NRTI治疗的患者。在治疗效果研究中，对初始方案的生物学预测因素进行调整对于避免混淆很重要。
