Abstract
Antiretroviral therapy (ART) controls human immunodeficiency virus 1 (HIV-1) replication and prevents disease progression but does not eradicate HIV-1. The persistence of a reservoir of latently infected cells represents the main barrier to a cure. “Shock and kill” is a promising strategy involving latency reversing agents (LRAs) to reactivate HIV-1 from latently infected cells, thus exposing the infected cells to killing by the immune system or clearance agents. Here, we review advances to the “shock and kill” strategy made through the nonhuman primate (NHP) model, highlighting recently identified latency reversing agents and approaches such as mimetics of the second mitochondrial activator of caspase (SMACm), experimental CD8+ T cell depletion, immune checkpoint blockade (ICI), and toll-like receptor (TLR) agonists. We also discuss the advantages and limits of the NHP model for HIV cure research and methods developed to evaluate the efficacy of in vivo treatment with LRAs in NHPs.
Highlights
Antiretroviral therapy (ART) controls human immunodeficiency virus 1 (HIV-1) replication and prevents disease progression but does not eradicate HIV-1
We found that plasma viral loads on ART did not significantly differ between macaques treated with GS-986 and ART-only controls, indicating that GS-986 did not serve as an latency reversing agents (LRAs) in this setting
The methods described above allow investigation into the source of viral reactivation on a level not possible in people living with HIV-1, highlighting a key contribution that the nonhuman primate (NHP) model of simian immunodeficiency virus (SIV) and simian/human immunodeficiency virus (SHIV) infection can make in the quest for an HIV-1 cure
Summary
NHPs have long been established as robust animal models of HIV-1 infection, revealing critical aspects of HIV-1 immunopathogenesis and providing outstanding platforms for vaccine research. These studies showed that viral RNA and DNA decreased on ART in lymphoid tissues but remained stable in the CNS of ART-suppressed rhesus macaque infants and identified the GI tract as a site of persistent low-level viral transcription during ART [25,26] This model allows the testing of potential HIV-1 cure strategies in a pediatric setting that is difficult to assess in humans [27]. Characterization of persisting proviruses in ART-suppressed rhesus macaques showed several differences in terms of sequence evolution as compared to HIV-1, including the detection of more frequent intact proviruses, a larger fraction of G-to-A hypermutations, and less frequent large internal deletions [33] Another key difference was the limited number of identical SIV sequences an earlier study using integration site analysis suggested similar clonal expansion of latently infected cells in macaques and humans [43].
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
