期刊
AMERICAN JOURNAL OF EPIDEMIOLOGY
卷 158, 期 7, 页码 687-694出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/aje/kwg206
关键词
acquired immunodeficiency syndrome; antiretroviral therapy; highly active; causality; confounding factors (epidemiology)
资金
- NCRR NIH HHS [5-M01-RR-00722, M01-RR00083] Funding Source: Medline
- NIAID NIH HHS [U01-AI-31834, U01-AI-34989, U01-AI-34993, U01-AI-34994, U01-AI-35004, U01-AI-35039, R01-AI-32475, K08-AI-49392, U01-AI-35040, U01-AI35042, U01-AI-42590, U01-AI-37984, U01-AI-37613, U01-AI-35043, U01-AI-35041] Funding Source: Medline
- NICHD NIH HHS [U01-HD-32632] Funding Source: Medline
To estimate the net (i.e., overall) effect of highly active antiretroviral therapy (HAART) on time to acquired immunodeficiency syndrome (AIDS) or death, the authors used inverse probability-of-treatment weighted estimation of a marginal structural model, which can appropriately adjust for time-varying confounders affected by prior treatment or exposure. Human immunodeficiency virus (HIV)-positive men and women (n = 1,498) were followed in two ongoing cohort studies between 1995 and 2002. Sixty-one percent (n = 918) of the participants initiated HAART during 6,763 person-years of follow-up, and 382 developed AIDS or died. Strong confounding by indication for HAART was apparent; the unadjusted hazard ratio for AIDS or death was 0.98. The hazard ratio from a standard time-dependent Cox model that included time-varying CD4 cell count, HIV RNA level, and other time-varying and fixed covariates as regressors was 0.81 (95% confidence interval: 0.61, 1.07). In contrast, the hazard ratio from a marginal structural survival model was 0.54 (robust 95% confidence interval: 0.38, 0.78), suggesting a clinically meaningful net benefit of HAART. Standard Cox analysis failed to detect a clear net benefit, because it does not appropriately adjust for time-dependent covariates, such as HIV RNA level and CD4 cell count, that are simultaneously confounders and intermediate variables.
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