Kinetics of HIV-1 RNA concentration changes in pediatric patients

Recent studies have used potent antiviral agents to investigate the kinetics of HIV infection in vivo. They provided estimates for important kinetic parameters, including the decay constants for circulating 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 values of the kinetic parameters through other means. Since CD4+ cells are known to exhibit diurnal variations and since there have been suggestions that circulating virus concentrations also vary in a diurnal fashion, 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 the model with experimental data we measured the temporal dependence of the concentration of plasma viral RNA obtained from pediatric HIV-1 patients. The data analysis led to finding diurnal variation in the viral RNA and an estimate of the circulating virus half-life in the order of few hours, in reasonable agreement with the estimates obtained using antiviral agents. These results are the first demonstration of diurnal variations in AIDS patients and confirm the order of magnitude of the virus half-life found by using antiviral drugs. These findings may have implications for understanding HIV-1 pathogenesis and the development of therapeutic protocols.