Targeting viral reservoirs: ability of antiretroviral therapy to stop viral replication

Maldarelli, Frank

Current Opinion in HIV & AIDS: January 2011 - Volume 6 - Issue 1 - p 49–56
doi: 10.1097/COH.0b013e32834134ea
HIV reservoirs: from pathogenesis to drug development: Edited by Robert F. Siliciano and Janet D. Siliciano

Purpose of review: HIV infection is controlled but not cured by combination antiretroviral therapy. HIV may persist for a number of reasons, including ongoing cycles of HIV infection or viral persistence as latent, or HIV replication in long-lived cells containing HIV proviruses. Therapeutic consequences of these alternative mechanisms are significant and distinct. If ongoing replication remains during current antiretroviral therapy, then improvements in potency will be useful in eradication strategies. Alternatively, long-lived cells with integrated proviruses will not be affected by improvements in therapy directed against active infection, and new strategies will be necessary for HIV eradication. Technologic advances have made it possible to carry out a series of drug intensification protocols in well suppressed patients; these and other analyses for HIV replication have been useful to elucidate the nature of HIV persistence on therapy.

Recent findings: A number of clinical studies intensifying antiretroviral therapy carried out in the last several years have yielded new findings regarding the ability to detect the presence of ongoing replication. Decreases in persistent viremia have not been consistently detected in individuals on potent combination antiretroviral therapy. Evidence for persistent replication has been reported in patients using sensitive assays of cell-associated HIV.

Summary: HIV viremia persists despite combination antiretroviral therapy. Antiretroviral drug intensification does not lower the level of HIV measured in plasma, suggesting current therapy arrests active virus replication. HIV eradication will most likely require therapy in addition to potent antiretroviral therapy.

HIV Drug Resistance Program, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA

Correspondence to Frank Maldarelli, Staff Physician, HIV Drug Resistance Program, National Cancer Institute, National Institutes of Health, Building 10 Rm 5A06, 10 Center Drive, Bethesda, MD 20892, USA Tel: +1 301 435 8019; fax: +1 301 480 1735; e-mail:

© 2011 Lippincott Williams & Wilkins, Inc.