Comparative Analysis Of HIV/SHIV Dynamics In Cultured Cells, Primary Infections In Monkeys And Humans Off Therapy

D.S. Dimitrov, I. Sidorov, R.A. Lempicki, J. Kovacs, R.T. Davey, H.C. Lane, J. Lifson and M.A. Martin

Analysis of HIV dynamics in acute infections is important for understanding mechanisms of pathogenesis and evaluation of vaccines. By titering HIV-1 in cultured cells we previously experimentally quantitated and mathematically described the dynamics of HIV-1 infection using a simple model based on virus dissemination by subsequent cycles of infection (1) and a more sophisticated model based on a system of differential equations (2,3). We found that an effective infection rate constant, k, ranging from 0.2 to 1.8 day-1 reproducibly and consistently characterized the dynamics of the initial stage of virus dissemination for a number of virus/cell systems (1). We and others (M. Feinberg and his collaborators) estimated values of k in the same range or even higher for primary SIV or SHIV infections in monkeys and found that they may or may not be correlated to clinical outcome (4 and citations therein). Recently, similar but somewhat lower values of k ranging from 0.12 to 0.91 day-1 were measured in humans with HIV-1 infections after interruption of HAART (5 and citations therein). The lower values of k could be due to immune responses, lower number of susceptible cells, lower susceptibility to infection or/and other reasons. These similarities and differences between the values of k (and several other parameters characterizing the dynamics of acute infections) for cultured cells and in vivo infections, and correlations with other virological and immunological parameters may help in the elucidation of the mechanisms of virus pathogenesis and evaluation of vaccines.

References

  1. Dimitrov, D.S., Willey, R.L., Sato, H., Chang, L.-Ji, Blumenthal, R., Martin, M.A. (1993) Quantitation of HIV-1 infection kinetics. J. Virology, 67, 2182-2190.
  2. Spouge, J.L., Shrager, R.I., Dimitrov, D.S. (1996) HIV-1 infection kinetics in tissue cultures. Bull Math Biosci, 138, 1-22.
  3. Dimitrov, D.S. (1998) Modeling HIV infection kinetics. In: Computer Modeling of Complex Biological Systems, edited by Iyengar, S.S., CRC Press, ch 6, pp. 79-100.
  4. Endo Y., Igarashi, T., Nishimura Y., Buckler C., Buckler-White A., Plishka R., Dimitrov D.S., Martin M.A. The short and long term clinical outcomes in rhesus monkeys inoculated with a highly pathogenic SIV/HIV chimeric virus, submitted.
  5. Davey R.T., Bhat N., Yoder C., Chun T., Metcalf J.A., Dewar R., Natarajan V., Lempicki R.A., Adelsberger J.W., Miller K.D., Kovacs J.A., Polis M.A., Walker R.E., Falloon J., Masur H., Gee D., Baseler M., Dimitrov D.S., Fauci A.S., Lane H.C. (1999) HIV-1 and T Cell Dynamics Following Interruption of HAART in Patients with a History of Sustained Viral Suppression. Proc Natl Acad Sci U S A, 96, 7496-7501.


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