Treatment interruption as a tool to measure changes in immunologic response to HIV-1

Abstract

Purpose of review: Introduction of potent combination antiretroviral therapy has led to the successful treatment of HIV infection, although adverse side effects, toxicities and drug resistance to currently available antiretroviral therapy regimens emerge, resulting in poorer outcomes. Alternative therapeutic interventions are needed to enhance HIV-1-specific immunity. The review will discuss the rationale for use of therapeutic immunization as a method to enhance HIV-1-specific immunity, and support the use of analytical treatment interruption to obtain and define immune correlates.

Recent findings: Results of recent studies using structured treatment interruption strategies demonstrate that with proper features to protect against drug resistance and drops in CD4 cell counts, viral endpoints following analytical treatment interruption can be used as a tool for measuring efficacy of immunologic therapeutic interventions. The viral rebound dynamics during and viral set points established following analytical treatment interruptions should be used as study endpoints as they represents the host's anti-HIV immune response to the therapeutic vaccine.

Summary: The results of recent treatment interruption studies support the use of an analytical treatment interruption as an effective tool to identify and define immune function correlates, and to generate data to support the subsequent conduct of larger, more definitive phase II/III studies.