Risks and benefits of structured antiretroviral drug therapy interruptionsin HIV-1 infection

Background: Structured interruptions of antiretroviral therapy of HIV-1 inf ected individuals are currently being tested in clinical trials to study th e effect interruptions have on the immune responses and control of virus re plication. Objective: To investigate the potential risks and benefits of interrupted t herapy using standard population dynamical models of HIV replication kineti cs. Methods: Standard population dynamical models were used to study the effect of structured therapy interruptions on the immune effector cells, the late nt cell compartment and the emergence of drug resistance. Conclusions: The models suggest that structured therapy interruption only l eads to transient or sustained virus control if the immune effector cells i ncrease during therapy. This increase must more than counterbalance the inc rease in susceptible target cells induced by therapy. The risk of inducing drug resistance by therapy interruptions or the risk of repopulating the po ol of latent cells during drug-free periods may be small if the virus popul ation remains at levels considerably below baseline. However, if the virus load increases during drug-free periods to levels similar to or higher than baseline before therapy, both these risks increase dramatically. (C) 2000 Lippincott Williams & Wilkins.