Highly active antiretroviral therapy (HAART) can reduce viremia to below the limit of detection of current clinical assays (50 copies of HIV RNA/mL plasma), but viral reservoirs and low level residual viremia persist. Recent studies of HAART intensification show that the residual viremia is not due to ongoing replication, but rather release from stable reservoirs. Pharmacodynamic studies of antiretroviral drugs have shown that some classes of drugs have steep dose response curves, reflecting a unique form of intermolecular cooperativity that allows for up to 10 logs of inhibition of a single round of replication by some of the best drugs. The development of methods for calculating the combined inhibitory potential of drug combinations has allowed for the first time a direct comparison of the antiviral activity of different drug regimens and the definition of a minimum threshold for effective HAART. This quantitative approach to understanding HAART may be useful in the choice of HAART regimens for patients with wild type and resistant virus.
(C) 2012 Lippincott Williams & Wilkins, Inc.