Modeling AIDS survival after initiation of antiretroviral treatment by Weibull models with changepoints

Abstract

Background: Mortality of HIV-infected patients initiating antiretroviral therapy in the developing world is very high immediately after the start of ART therapy and drops sharply thereafter. It is necessary to use models of survival time that reflect this change. Methods: In this endeavor, parametric models with changepoints such as Weibull models can be useful in order to explicitly model the underlying failure process, even in the case where abrupt changes in the mortality rate are present. Estimation of the temporal location of possible mortality changepoints has important implications on the effective management of these patients. We briefly describe these models and apply them to the case of estimating survival among HIV-infected patients who are initiating antiretroviral therapy in a care and treatment programme in sub-Saharan Africa. Results: As a first reported data-driven estimate of the existence and location of early mortality changepoints after antiretroviral therapy initiation, we show that there is an early change in risk of death at three months, followed by an intermediate risk period lasting up to 10 months after therapy. Conclusion: By explicitly modelling the underlying abrupt changes in mortality risk after initiation of antiretroviral therapy we are able to estimate their number and location in a rigorous, data-driven manner. The existence of a high early risk of death after initiation of antiretroviral therapy and the determination of its duration has direct implications for the optimal management of patients initiating therapy in this setting.