DEVELOPMENT OF A MONKEY MODEL FOR TESTING OF ANTIVIRAL AGENTS AGAINST HIV1

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A good animal model for HIV-1 is essential for AIDS vaccine studies and development of efficacious anti-viral agents. Pig-tailed macaques have been found to be susceptible to HIV-1 infection (Agy, et al., 1992). Based upon this initial report, we previously infected 2 pig-tailed macaques (designated as PT86 and PT99) with HIV-1/LAI and have monitored long-term infection and clinical changes. Each animal responded uniquely to the infection. In the case of PT86 viral sequences (DNA and RNA) were detected in the PBMC in the first year whereas the lymph nodes were positive even at 3 years P.I. Antibodies to HIV-1 gag and env proteins have persisted in PT86 at 5 years post-infection although a decrease in the gag antibodies was seen. The CD4+/CD8+ ratio continues to gradually decline. In the case of PT99 viral DNA sequences were seen in the PBMCs up to 1 year and in the lymph node 3 years PI. Antibodies to the env proteins have persisted at 5 year PI. The CD4+/CD8+ ratio remained stable. No clinical symptoms have developed in PT86 or PT99. Since the clinical symptoms of AIDS in humans generally develop in 5-10 years and developed after about 10 years post-infection in one chimpanzee, it is most likely too early to see clinical symptoms in the infected pig-tailed macaques. The results thus far indicate that HIV-1 infection of pig-tailed macaques may be similar to the infection seen in some humans: in the case of PT99 the infection is non-progressing whereas PT86 might represent a long-term survivor. The pig-tailed macaque model will be used to evaluate protection by HIV-1 plasmid DNA vaccine against homologous challenge virus infection (HIV-1/LAI).