Outcomes for therapeutic vaccines trials.
OBJECTIVE
This article briefly reviews the concept of therapeutic vaccination in HIV management, with a focus on the outcomes measures for clinical trials. In light of new information on the adverse consequences of uncontrolled viral replication during treatment interruption, outcome measures used in some recent trials are compared with current standards for antiretroviral therapy.


RESULTS
Immunogenicity may not translate to clinical benefit. Experimental therapeutic vaccines that were preliminarily shown to be immunogenic failed to control viral replication on further investigation. Two major studies of structured treatment interruption - an intervention that bears some similarities to therapeutic immunization - were prematurely discontinued by data safety and monitoring boards because of worse morbidity or mortality among patients whose treatments were interrupted. Uncontrolled viral replication was probably culpable in the adverse outcomes.


CONCLUSIONS
The design of therapeutic vaccine clinical trials has not kept pace with clinical standards for HIV care. Future trials should evaluate immunogenicity, but also investigate the impact of vaccine-induced immune responses on viral replication and the clinical course. Ideally, the studies should aim to demonstrate non-inferiority to uninterrupted, fully suppressive highly active antiretroviral therapy and define virological failure as a sustained plasma viral load greater than 50-400 copies/ml.
Taiwo
Babafemi
B
Division of Infectious Diseases, Feinberg School of Medicine Northwestern University, Chicago, Illinois, USA. b-taiwo@northwestern.edu
Murphy
Robert
R