KINETICS OF HIV-1 RNA CONCENTRATION CHANGES IN PEDIATRIC-PATIENTS

Recent studies have used potent antiviral agents to investigate the ki netics of HIV infection in vivo [1-3]. They provided estimates for imp ortant kinetic parameters, including the decay constants for circulati ng virus and infected CD4+ cells. However, since all of these studies fundamentally rely on the use of antiviral agents, it would be useful to develop other approaches capable of independently verifying the val ues of the kinetic parameters through other means. Since CD4+ cells ar e known to exhibit diurnal variations and since there have been sugges tions that circulating virus concentrations also vary in a diurnal fas hion, as well as nonperiodically, we developed a mathematical model to describe those natural variations. The model predicted variations in viral RNA concentrations and produced estimates of the values of viral kinetic parameters without the use of antiviral agents. To compare th e model with experimental data we measured the temporal dependence of the concentration of plasma viral RNA obtained from pediatric HIV-1 pa tients. The data analysis led to finding diurnal variation in the vira l RNA and an estimate of the circulating virus half-life in the order of few hours, in reasonable agreement with the estimates obtained usin g antiviral agents. These results are the first demonstration of diurn al variations in AIDS patients and confirm the order of magnitude of t he virus half-life found by using antiviral drugs [3]. These findings may have implications for understanding HIV-1 pathogenesis and the dev elopment of therapeutic protocols.