DEVELOP MODEL OF PNEUMOCYSTIS CARINII PNEUMONIA IN RHESUS MONKEY: SIV

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Pneumocystis carinii pneumonia (PCP) is the most frequently reported opportunistic infectious complication in HIV infected individuals. Numerous rodent models of PCP are available. Occasionally PCP occurs in the simian immunodeficiency virus (SIV) infected rhesus monkey during the later immunosuppressive phase of disease. Unfortunately, the occurance of PCP is not predictable in SIV infected animals due to individual host variablility, different SIV strains used, and because of differences in prevalence of P. carinii in the environment. A reproducible model of PCP in rhesus monkeys could be utilized to study the pathogenesis of the disease and to allow drug therapy trials. Using previously published information on the PCP mouse model, we undertook a pilot study using dexamethasone to immunosuppress two rhesus monkeys. The animals were housed conventionally in a room in single cages. We followed the animals clinically by daily observation, weekly physical examination, weekly complete blood counts (CBC) and weekly serum chemistries. Dosing was instituted at 2.5 mg/kg IM every 12 hours. The dose was tapered over an eight week period to 0.5 mg/kg/day. Prophylactic antibiotic therapy was administered during treatment. Absolute lymphopenia occurred in both animals within the first week of dosing. Lymphocyt counts returned to normal by 35 days of treatment. This time point corresponded with the tapered dosing of 0.5 mg/kg/day. At no time during dosing was neutropenia noted. Physical examination revealed weight loss in both animals. One animal demondstrated failure to epithelialize a deep self-trauma bite wound that occurred during the initial days of the study. This wound later became infected and required discontinuation of dexamethasone and intensive multiple drug antibiotic therapy to cure. Future experiments will utilize conbination immunosuppressive drug protocols to minimize complications associated with high dose corticosteriod administration. The use of laminar flow housing will also be explored as well as the use of a broader spectrum