TY - JOUR
T1 - Effect of highly active antiretroviral therapy on time to acquired immunodeficiency syndrome or death using marginal structural models
AU - Cole, Stephen R.
AU - Hernán, Miguel A.
AU - Robins, James M.
AU - Anastos, Kathryn
AU - Chmiel, Joan
AU - Detels, Roger
AU - Ervin, Carolyn
AU - Feldman, Joseph
AU - Greenblatt, Ruth
AU - Kingsley, Lawrence
AU - Lai, Shenghan
AU - Young, Mary
AU - Cohen, Mardge
AU - Muñoz, Alvaro
N1 - Funding Information:
The Multicenter AIDS Cohort Study is funded by the National Institute of Allergy and Infectious Diseases, with additional supplemental funding from the National Cancer Institute (grants UO1-AI-35042, 5-MO1-RR-00722 (General Clinical Research Center), UO1-AI-35043, UO1-AI-37984, UO1-AI-35039, UO1-AI-35040, UO1-AI-37613, and UO1-AI-35041). The Women’s Interagency HIV Study is funded by the National Institute of Allergy and Infectious Diseases, with supplemental funding from the National Cancer Institute, the National Institute of Child Health and Human Development, the National Institute on Drug Abuse, the National Institute of Dental and Craniofacial Research, the Agency for Health Care Policy and Research, and the Centers for Disease Control and Prevention (grants U01-AI-35004, U01-AI-31834, U01-AI-34994, U01-AI-34989, U01-HD-32632 (National Institute of Child Health and Human Development), U01-AI-34993, U01-AI-42590, and M01-RR00083). (Study websites are located at http:// www.statepi.jhsph.edu.) Dr. Miguel Hernán was supported by National Institutes of Health grant K08-AI-49392, and Dr. James Robins was supported by National Institutes of Health grant R01-AI-32475.
PY - 2003/10/1
Y1 - 2003/10/1
N2 - 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.
AB - 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.
KW - Acquired immunodeficiency syndrome
KW - Antiretroviral therapy
KW - Causality
KW - Confounding factors (epidemiology)
KW - Highly active
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U2 - 10.1093/aje/kwg206
DO - 10.1093/aje/kwg206
M3 - Article
C2 - 14507605
AN - SCOPUS:0141620176
SN - 0002-9262
VL - 158
SP - 687
EP - 694
JO - American Journal of Epidemiology
JF - American Journal of Epidemiology
IS - 7
ER -