Characterizing features of the viral rebound trajectories and identifying host, virological, and immunological factors that are predictive of the viral rebound trajectories are central to HIV cure research. In this paper, we investigate if key features of HIV viral decay and CD4 trajectories during antiretroviral therapy (ART) are associated with characteristics of HIV viral rebound following ART interruption. Nonlinear mixed effect (NLME) models are used to model viral load trajectories before and following ART interruption, incorporating left censoring due to lower detection limits of viral load assays. A stochastic approximation EM (SAEM) algorithm is used for parameter estimation and inference. To circumvent the computational intensity associated with maximizing the joint likelihood, we propose an easy-to-implement three-step method. We evaluate the performance of this method through simulation studies and apply it to data from the Zurich Primary HIV Infection Study. We find that some key features of viral load and CD4 trajectories during ART (e.g., viral decay rate) are significantly associated with important characteristics of viral rebound following ART interruption (e.g., viral set point).
Gao, Sihaoyu; Wu, Lang; Yu, Tingting; Kouyos, Roger; Gunthard, Huldrych F.; and Wang, Rui, "Nonlinear Mixed-Effects Models for HIV Viral Load Trajectories Before and After Antiretroviral Therapy Interruption, Incorporating Left Censoring" (December 2021). Harvard University Biostatistics Working Paper Series. Working Paper 232.