HIV Reservoirs: Modeling, Quantification, and Approaches to a Cure.

Biomedical research in animal models depends heavily on nonhuman primates (NHP) (Phillips et al., Am J Primatol 76(9):801-827, 2014). In their physiology, neurobiology, and, most importantly, their susceptibility to infectious diseases and subsequent immune responses, NHPs have many parallels with humans (Rhesus Macaque Genome Sequencing and Analysis Consortium et al., Science 316(5822):222-234, 2007). Different species of NHPs have served as important animal models for numerous infectious diseases spanning a wide range of pathogens (Gardner and Luciw, ILAR J 49(2):220-255, 2008). As a result of recognizing their utility in HIV research, NHPs have contributed to groundbreaking studies of disease pathogenesis, vaccination, and curative research (London et al., Lancet 2(8355):869-873, 1983; Henrickson et al., Lancet 1 (8321):388-390, 1983). Many African NHPs are considered natural hosts for SIV in which SIV infection is usually nonprogressive and does not cause acquired immunodeficiency syndrome (AIDS) (Chahroudi et al., Science 335(6073):1188-1193, 2012; Taaffe et al., J Virol 84(11):5476-5484, 2010). However, cross-species transmission of SIV strains to other NHPs or to humans (nonnatural hosts) leads to progressive disease and AIDS (Paiardini et al., Annu Rev Med 60:485-495, 2009). In particular, SIV infection of Asian rhesus macaques recapitulates many features of HIV infection in humans and therefore has become a widely used approach for contemporary HIV research into virus persistence and cure strategies (Gardner and Luciw, FASEB J 3(14):2593-2606, 1989). There are multiple factors that should be considered in HIV/SIV studies using NHPs including the particular monkey species and geographic background, age and sex, certain genetic properties, virus strain, route and dose of infection, interventional treatments, and prespecified study outcomes. Here, we discuss consideration of these factors to address specific questions in HIV cure research.