HIV-1 DYNAMICS AFTER TRANSIENT ANTIRETROVIRAL THERAPY - IMPLICATIONS FOR PATHOGENESIS AND CLINICAL MANAGEMENT

Simple models of CD4 lymphocyte interactions with human immunodeficien cy virus (HIV) lead to the hypothesis that progression of HIV infectio n involves an increase in viral replicative capacity, due either to ch anges in the virus or in the host environment, or both. In order to co nsider how changes in plasma virus load after transient, potent antire troviral therapy can be used to test the above hypothesis-a simple mat hematical model that encompasses the processes of(1) arrival of new CD 4 lymphocytes, (2) death/removal of these cells by HIV-independent mec hanisms, (3) infection of susceptible CD4 lymphocytes by HIV, and (4) death/removal of infected cells was investigated. This showed that the in vivo rate of increase in plasma virus load immediately after trans ient therapy provides a measure of the viral replicative capacity. Thu s, the hypothesis that progression of HIV infection involves an increa se in viral replicative capacity can be tested by measuring this viral growth rate in patients with high CD4 counts and in patients with low CD4 counts. Studies should thus investigate dynamics of changes in vi rus levels after stopping antiretroviral therapy a nd, in particular, measure rates of increase in virus in patients at high and low CD4 cou nts. In practice, such data may assist in therapeutic management of pa tients with HIV infection. (C) 1997 Wiley-Liss, Inc.