American Journal of Epidemiology Advance Access published online on November 24, 2009
American Journal of Epidemiology, doi:10.1093/aje/kwp329
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Practice of Epidemiology |
Using Marginal Structural Measurement-Error Models to Estimate the Long-term Effect of Antiretroviral Therapy on Incident AIDS or Death
* Correspondence to Dr. Stephen R. Cole, University of North Carolina Gillings School of Global Public Health, MacGavran-Greenberg Hall, CB#7435, Chapel Hill, NC 27599-7435 (e-mail: cole{at}unc.edu).
Received for publication March 25, 2009. Accepted for publication September 16, 2009.
To estimate the net effect of imperfectly measured highly active antiretroviral therapy on incident acquired immunodeficiency syndrome or death, the authors combined inverse probability-of-treatment-and-censoring weighted estimation of a marginal structural Cox model with regression-calibration methods. Between 1995 and 2007, 950 human immunodeficiency virus–positive men and women were followed in 2 US cohort studies. During 4,054 person-years, 374 initiated highly active antiretroviral therapy, 211 developed acquired immunodeficiency syndrome or died, and 173 dropped out. Accounting for measured confounders and determinants of dropout, the weighted hazard ratio for acquired immunodeficiency syndrome or death comparing use of highly active antiretroviral therapy in the prior 2 years with no therapy was 0.36 (95% confidence limits: 0.21, 0.61). This association was relatively constant over follow-up (P = 0.19) and stronger than crude or adjusted hazard ratios of 0.75 and 0.95, respectively. Accounting for measurement error in reported exposure using external validation data on 331 men and women provided a hazard ratio of 0.17, with bias shifted from the hazard ratio to the estimate of precision as seen by the 2.5-fold wider confidence limits (95% confidence limits: 0.06, 0.43). Marginal structural measurement-error models can simultaneously account for 3 major sources of bias in epidemiologic research: validated exposure measurement error, measured selection bias, and measured time-fixed and time-varying confounding.
acquired immunodeficiency syndrome; bias (epidemiology); cohort studies; confounding factors (epidemiology); epidemiologic measurements; HIV; pharmacoepidemiology; selection bias
Abbreviations: AIDS, acquired immunodeficiency syndrome; CL, confidence limits; HAART, highly active antiretroviral therapy; HIV, human immunodeficiency virus; IPTC, inverse probability of treatment and censoring; MACS, Multicenter AIDS Cohort Study; SE, standard error