Simian Immunodeficiency Virus (SIV) rebound observed in the rhesus macaque model four days after antiretroviral therapy interruption
Stroupe, Claudia C.
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While antiretroviral therapy (ART) effectively suppresses simian immunodeficiency virus (SIV) replication in infected individuals, the virus maintains its presence within the body through the integration of replication-competent proviruses with the body’s own cells. Consequently, when ART is interrupted these cells, which constitute the latent reservoir, switch from latency to active SIV production. Given current knowledge on latent reservoirs, this study attempted to define where latently infected cells can be found, and at what point viral rebound can be seen in tissues. Four Rhesus Macaques were infected with SIVmac239ff via vaginal and rectal challenges, and placed on ART for days after infection for six months. Following ART cessation, the macaques waited 4, 5, 7, or 10 days before undergoing PET/CT scans, necropsy, and tissue staining for viral envelope and gag. Infected cells were found in the ascending colon, vagina, and mesenteric lymph nodes. Moreover, active SIV infection begins rapidly after ART interruption, with strong PET/CT signal and high infected cell count seen within four days of ART cessation. These results underscore the robustness of SIV rebound and the challenges faced by the scientific community in the search for a cure for HIV. Multiple tissue types are susceptible to recruitment as reservoir cells, and are acutely responsive to ART cessation. On the whole, both the widespread nature of these reservoirs, as well as the sensitivity and intensity of rebound indicate that while targeting latent reservoirs may be key to the understanding HIV’s evasion of immune responses, and extensive establishment in the body, there is much to learn about the dynamics of rebound and the role of latent reservoirs.