Abstract
HIV infection requires lifelong antiretroviral therapy (ART) to control disease progression. Although ART has greatly extended the life expectancy of persons living with HIV (PWH), PWH nonetheless suffer from an increase in AIDS-related and non-AIDS related comorbidities resulting from HIV pathogenesis. Thus, an HIV cure is imperative to improve the quality of life of PWH. In this review, we discuss the origins of various SIV strains utilized in cure and comorbidity research as well as their respective animal species used. We briefly detail the life cycle of HIV and describe the pathogenesis of HIV/SIV and the integral role of chronic immune activation and inflammation on disease progression and comorbidities, with comparisons between pathogenic infections and nonpathogenic infections that occur in natural hosts of SIVs. We further discuss the various HIV cure strategies being explored with an emphasis on immunological therapies and “shock and kill”.
Highlights
Introduction and the Origin of SIVmacIn the early 1970s, an outbreak of lymphomas, resembling Burkitt’s lymphoma, was reported in RMs housed at the California National Primate Research Center (CNPRC) [9,10,11,12] and would later be demonstrated to play a role in the SIVmac infections at New England Regional Primate Research Center (NEPRC)
The virus isolated from the macaques in NEPRC and CNPRC was closely related to the simian immunodeficiency virus (SIV) naturally infecting sooty mangabeys (Cercocebus atys, SM) [19]
In conjunction with data demonstrating that immune activation rapidly decreases with antiretroviral therapy (ART), it is likely that viral loads (VLs) is one of the drivers of the immune activation set-point [139,140,141]
Summary
In the early 1970s, an outbreak of lymphomas, resembling Burkitt’s lymphoma, was reported in RMs housed at the California National Primate Research Center (CNPRC) [9,10,11,12] and would later be demonstrated to play a role in the SIVmac infections at NEPRC. Direct passaging of SIVsab92018 (SIVsab) into RMs results in a state of functional cure, whereby the RMs naturally control the virus replication to below the limits of detection, immune populations are restored during chronic infection, and immune activation and inflammation (IA/INFL) are controlled back to baseline levels [71,72] We utilize this model for experimental agent testing due to the ability to reactivate virus and bolster viral production by de novo infection off of antiretrovirals, thereby increasing resolution of viral reactivation. Even the CCR5-tropic SHIVs are not necessarily ideal due to the use of env sequences from chronically infected PWH and their passaging in NHPs results in modified env sequences [82,84,90] They are not as clinically relevant for vaccine studies as transmitted founder (TF) viruses which have special characteristics that increase fitness, and importantly, will have the relevant Env for targeting in vaccine or antibody studies [91]. The study of the early events of HIV/SIV transmission showed that the immune response to infection is a double-edged sword: it helps establish the transmission bottleneck and eliminate virus, but the cellular activation contributes to infection by increasing the amount of target cells at the site of entry [117]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
