Quantification of in vivo replicative capacity of HIV-1 in different compartments of infected cells

Based on a mathematical model, we analyze the dynamics of CD4(+) cells, act ively, latently, persistently, and defectively infected cells and plasma vi rus after initiation of antiretroviral therapy in 14 HIV-1-infected asympto matic patients. By simultaneous fitting of our model to clinical data of pl asma HIV-1 RNA, peripheral blood mononuclear cell (PBMC)-gag RNA, proviral DNA, and CD4(+) cell counts, we estimate kinetic parameters to determine th e basic reproductive rate (R-0) of the virus in different infected cell com partments as a measure of the replicative capacity of the virus in vivo. We find that the basic reproductive rate is larger than 1 before treatment on ly in actively infected cells (mean R-0(act) approximate to 2.46) indicatin g that only in this compartment the virus can maintain an ongoing infection . In latently and persistently infected cells the basic reproductive rate i s considerably smaller (R-0(lat) approximate to 0.03 and R-0(pers) approxim ate to 0.008, respectively) indicating that these compartments contribute l ittle to the total basic reproductive rate and cannot maintain an ongoing i nfection in absence of actively infected cells.