Marginal Structural Models for Estimating the Effect of Highly Active Antiretroviral Therapy Initiation on CD4 Cell Count

Authors:
  • MHMiguel A. Hernán
    Miguel A. Hernán
  • JMJoseph B. Margolick
    Joseph B. Margolick
  • MCMardge H. Cohen
    Mardge H. Cohen
  • JRJames M. Robins
    James M. Robins
Open Access
Publisher website
Google Scholar
Abstract
The effect of highly active antiretroviral therapy (HAART) on the evolution of CD4-positive T-lymphocyte (CD4 cell) count among human immunodeficiency virus (HIV)-positive participants was estimated using inverse probability-of-treatment-and-censoring (IPTC)-weighted estimation of a marginal structural model. Of 1,763 eligible participants from two US cohort studies followed between 1996 and 2002, 60 percent initiated HAART. The IPTC-weighted estimate of the difference in mean CD4 cell count at 1 year among participants continuously treated versus those never treated was 71 cells/mm3 (95% confidence interval: 47.5, 94.6), which agrees with the reported results of randomized experiments. The corresponding estimate from a standard generalized estimating equations regression model that included baseline and most recent CD4 cell count and HIV type 1 RNA viral load as regressors was 26 cells/mm3 (95% confidence interval: 17.7, 34.3). These results indicate that nonrandomized studies of HIV treatment need to be analyzed with methods (e.g., IPTC-weighted estimation) that, in contrast to standard methods, appropriately adjust for time-varying covariates that are simultaneously confounders and intermediate variables. The 1-year estimate of 71 cells/mm3 was followed by an estimated continued increase of 29 cells/mm3 per year (estimated effect at 6 years: 216 cells/mm3), providing evidence that the large short-term effect found in randomized experiments persists and continues to improve over 6 years.

This publication has 25 references indexed in Scilit: