Evaluation of antiretrovirals in animal models of HIV infection

Animal models of HIV infection have played an important role in the development of antiretroviral drugs. Although each animal model has its limitations and never completely mimics HIV infection of humans, a carefully designed study allows experimental approaches that are not feasible in humans, but that can help to better understand disease pathogenesis and to provide proof-of-concept of novel intervention strategies. While rodent and feline models are useful for initial screening, further testing is best done in non-human primate models, such as simian immunodeficiency virus (SIV) infection of macaques, because they share more similarities with HIV infection of humans. In the early years of the HIV pandemic, non-human primate models played a relatively minor role in the antiretroviral drug development process. Since then, a better understanding of the disease and the development of better drugs and assays to monitor antiviral efficacy have increased the usefulness of the animal models. In particular, non-human primate models have provided proof-of-concept for (i) the benefits of chemoprophylaxis and early treatment, (ii) the preclinical efficacy of novel drugs such as tenofovir, (iii) the virulence and clinical significance of drug-resistant viral mutants, and (iv) the role of antiviral immune responses during drug therapy. Ongoing comparison of results obtained in animal models with those observed in human studies will further validate and improve these animal models so they can continue to help advance our scientific knowledge and to guide clinical trials. This article forms part of a special issue of Antiviral Research marking the 25th anniversary of antiretroviral drug discovery and development, Vol 85, issue 1, 2010.