CLINICAL-FEATURES AND PREDICTIVE MARKERS OF DISEASE PROGRESSION IN CYNOMOLGUS MONKEYS EXPERIMENTALLY INFECTED WITH SIMIAN IMMUNODEFICIENCY VIRUS

Objective: To study the pathogenicity of simian immunodeficiency virus (SIV(sm)) in cynomolgus monkeys in order to establish an animal model for human AIDS. Methods: Thirty-three cynomolgus monkeys were monitored for more than 2 years following experimental infection with SIV(sm). Results: All the macaques became SIV-infected, as demonstrated by virus recovery from peripheral blood lymphocytes and by the appearance of viral antibodies. SIV(sm) was found to be pathogenic, killing 29 out of the 33 monkeys (88%) within 26 months. Clinically, infected monkeys developed lymphadenopathy, splenomegaly, diarrhoea, weight loss, neurological symptoms and a remarkably high incidence (39%) of malignant lymphomas. All lymphomas were high-grade malignant and of B-cell origin. Disease progression was associated with low CD4+ lymphocyte count, involution of initially hyperplastic follicular B-cell areas in lymph nodes, reappearance of viral antigen in serum, loss of anti-Gag antibodies and development of systemic giant cell disease in 55% of the monkeys. Conclusions: There are many similarities between SIV(sm)-induced AIDS in cynomolgus monkeys and human AIDS with regard to clinical, virological, immunological and pathological manifestations.