Effect of highly active antiretroviral therapy on time to acquired immunodeficiency syndrome or death using marginal structural models

Stephen R. Cole, Miguel A. Hernán, James M. Robins, Kathryn Anastos, Joan Chmiel, Roger Detels, Carolyn Ervin, Joseph Feldman, Ruth Greenblatt, Lawrence Kingsley, Shenghan Lai, Mary Young, Mardge Cohen, Alvaro Muñoz

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)687-694
Number of pages8
JournalAmerican Journal of Epidemiology
Volume158
Issue number7
DOIs
StatePublished - Oct 1 2003

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Keywords

  • Acquired immunodeficiency syndrome
  • Antiretroviral therapy
  • Causality
  • Confounding factors (epidemiology)
  • Highly active

ASJC Scopus subject areas

  • Epidemiology

Cite this

Cole, S. R., Hernán, M. A., Robins, J. M., Anastos, K., Chmiel, J., Detels, R., Ervin, C., Feldman, J., Greenblatt, R., Kingsley, L., Lai, S., Young, M., Cohen, M., & Muñoz, A. (2003). Effect of highly active antiretroviral therapy on time to acquired immunodeficiency syndrome or death using marginal structural models. American Journal of Epidemiology, 158(7), 687-694. https://doi.org/10.1093/aje/kwg206