HIV-1 infection and low steady state viral loads

Highly active antiretroviral therapy (HAART) reduces the viral burden in human immunodeficiency virus type 1 (HIV-1) infected patients below the threshold of detectability. However, substantial evidence indicates that viral replication persists in these individuals. In this paper we examine the ability of several biologically motivated models of HIV-1 dynamics to explain sustained low viral loads. At or near drug efficacies that result in steady state viral loads below detectability, most models are extremely sensitive to small changes in drug efficacy. We argue that if these models reflect reality many patients should have cleared the virus, contrary to observation. We find that a model in which the infected cell death rate is dependent on the infected cell density does not suffer this shortcoming. The shortcoming is also overcome in two more conventional models that include small populations of cells in which the drug is less effective than in the main population, suggesting that difficulties with drug penetrance and maintenance of effective intracellular drug concentrations in all cells susceptible to HIV infection may underlie ongoing viral replication. (C) 2002 Society for Mathematical Biology.