Two preprints are now available by electronic mail:
1. Anderson RW.
Mathematical models of HIV pathogenesis.
Nature Medicine, 3(9):936-7 (1997).
[commentary on Grossman and Herberman (1997)]
2. Russell W. Anderson, Michael S. Ascher, and Haynes W. Sheppard
Direct HIV cytopathicity cannot account for CD4 decline in AIDS
in the presence of homeostasis. A worst-case dynamical analysis
J. AIDS & Human Retroviruses (in press: 1997)
[Abstract below]
If you would like to receive a text version of either paper,
please contact me at the address below:
Russell W. Anderson
Smith-Kettlewell Eye Research Institute
2232 Webster Street
San Francisco, CA 94115
Office: (415) 561-1715
FAX: (415) 561-1610
anderson at skivs.ski.org
or
rwa at milo.berkeley.eduhttp://www.geocitites.com/Athens/4155
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ABSTRACT
The central paradox of HIV pathogenesis is that the viral burden
(either free or cellular) seems far too low to deplete the CD4
population by direct killing. Until recently, there were few data which
could be used to critically compare direct and indirect pathogenic
theories. Clinical trials with potent new antiviral agents have
measured important kinetic parameters of HIV infection, including viral
and infected cell half-lives. This has led to the construction of
explicit models of direct killing. Using a worst-case dynamical
analysis, we show that such cytopathic models are untenable.
Rates of infected cell removal are orders of magnitude too low to
significantly suppress steady state CD4 counts in the face of
lymphocyte replenishment, especially in early infection. Furthermore,
the direct cytopathic models, as proposed, predict an extremely
variable disease course across the broad range of observed
viral burdens (five orders of magnitude), which is inconsistent
with the relatively small differences in disease progression
observed between patients. In contrast, immunological theories
of pathogenesis, such as homeostatic dysregulation based on
immune activation, do not suffer from these difficulties
and are more consistent with the natural history of HIV infection.
