Shytaj et al.[1] report that complete suppression of SIVmac replication can be achieved in rhesus macaques by a combination of five antiretroviral (ARV) drugs, which the authors term ‘‘mega-HAART’’. This combination consists of the threedrug nucleoside reverse transcriptase inhibitor (tenofovir/emtricitabine) and integrase inhibitor (raltegravir) regimen often used in treatment studies of simian immunodeficiency virus (SIV)-infected rhesus macaques, intensified with the protease inhibitor darunavir (pharmacokinetically enhanced by ritonavir) and the CCR5 antagonist maraviroc. Achieving complete suppression of SIVmac in rhesus macaques is an important step in developing an animal model for HIV-1 cure research because it parallels the effects of antiretroviral therapy in HIV-infected humans. Without complete suppression, testing of therapeutic strategies to reduce viral reservoirs is confounded by ongoing cycles of viral replication that can replete such reservoirs.

Over the last two decades, rhesus macaque models of AIDS have revealed key aspects of HIV-1 pathogenesis, such as virus transmission and early events postinfection, the sites of viral replication and CD4+ T cell depletion, and virus and cell turnover [2–8]. These models have also been instrumental for vaccine research, allowing the evaluation of increasingly potent DNA and vector immunogens and combinations of these vectors in various prime-boost combinations [9–11]. Macaque models of preexposure prophylaxis (PrEP) have also helped elucidate the ARV exposures and the timing of exposure required to maximize protection from virus challenge [12].