Having established the chimpanzee as an animal model for HIV infection, in the second phase of our studies, emphasis is being placed on establishing a reproducible disease model for AIDS. To induce clinical manifestations, conditions simulating the human experience have been employed, namely repeated inoculation of virus, confection with other viruses, and immunologic stimulation. In the second phase of this study, we attempted to induce a reproducible disease model and to assess the parameters in addition to HIV, which may be essential to disease development. We have evaluated the use of repeated virus inoculation and the effect of repeated antigenic stimulation primarily in the form of factor VIII concentrates. We also have looked at the effect of simultaneous CMV, HBV, and NANBV infection. None of these manipulations has resulted in a consistent disease model. In the third phase of studies, we exposed the animals to large volume allogeneic stimulation by the cross-transfusion of allogenic lymphocytes that contain class I and class II determinants. This too has failed to induce HIV related disease. Currently, we are conifecting animals with Mycoplasma Ferientans which has recently been proposed as a cofactor in Human AIDS. In addition we are using the chimpanzee model to assess the early events of HIV infection and to determine if any new test parameters can narrow the early window of HIV infectivity. This study shows that HIV infection evident by culture and PCR within 4 weeks of exposure, but not evident by antibody seroconversion until 9 weeks after exposure. Testing for p-24 antigen did not reduce the serologic window.
