Antiretroviral drug studies in nonhuman primates: a valid animal model for innovative drug efficacy and pathogenesis experiments.

Several nonhuman primate models are used in HIV and AIDS research. In contrast to HIV-1 infection of chimpanzees, infection of macaque species with simian immunodeficiency virus (SIV) isolates results in a disease (simian AIDS) that shares many similarities with HIV infection and AIDS in humans. Although each animal model has its limitations and can never completely mimic HIV infection of humans, a carefully designed study allows experimental approaches, such as the control of certain variables, that are not feasible in humans, but that are often the most direct way to gain better insights in disease pathogenesis and provide proof-of-concept for novel intervention strategies. In the early days of the HIV pandemic, nonhuman primate models played a relatively minor role in the anti-HIV drug development process. During the past decade, however, the development of better virologic and immunologic assays, a better understanding of disease pathogenesis, and the availability of better drugs have made these animal models more practical for drug studies. In particular, nonhuman primate models have played an important role in demonstrating: (i) preclinical efficacy of novel drugs such as tenofovir; (ii) the benefits of chemoprophylaxis, early treatment and immunotherapeutic strategies; (iii) the virulence and clinical significance of drug-resistant viral mutants; and (iv) the role of antiviral immune responses during drug therapy. Comparison of results obtained in primate models with those observed in human studies will lead to further validation and improvement of these animal models. Accordingly, well-designed drug studies in nonhuman primates can continue to provide a solid scientific basis to advance our scientific knowledge and to guide future clinical trials.