Effect of discontinuing antiretroviral therapy on survival of women initiated on highly active antiretroviral therapy

Objective: To estimate the effect of discontinuing antiretroviral therapy (ART) on survival, among women who initiated highly active antiretroviral therapy (HAART). Design: A multicenter cohort study. Methods: A total of 951 HAART-initiated women were followed for total mortality between 1995 and 2002. The relative hazard (RH) of death attributable to discontinuing all ART was estimated using an inverse probability of treatment-weighted marginal structural Cox proportional hazards model, as well as standard Cox models. Results: Three hundred and forty-three out of 951 women discontinued all ART during the 3187 person-years of follow-up, and 116 died. The RH of death attributable to discontinuation was 1.97 [95% confidence interval (CI) 1.17, 3.31] from the marginal structural Cox model. A RH of 1.49 (95% CI 0.94, 2.35) was observed using the same set of covariates in a standard Cox model. Conclusion: An increased risk of mortality for those HAART initiators who discontinued ART was observed using a marginal structural Cox model. This increased risk was independent of measured treatment failure, and was greatly attenuated in a standard Cox model with time-varying covariates.