Effect of Combination Antiretroviral Therapy on Chinese Rhesus Macaques of Simian Immunodeficiency Virus Infection

Abstract

Definitive treatment of HIV infection remains a critical but elusive goal, with persistence of residual virus even in the face of prolonged administration of suppressive combination antiretroviral treatment (cART) providing a source for recrudescent infection if treatment is stopped. Characterization of the residual virus and devising strategies to target it for eradication are key goals in HIV treatment research. Indian rhesus macaques (In-RM) infected with SIVmac have been widely used in such research. However, it has proven challenging to achieve and sustain clinically relevant levels of suppression (< 30 vRNA copies/ml plasma) with cART in such models. As ease of viral suppression by cART is related to pretreatment levels of viral replication, and levels of replication of SIVmac239/251 are lower in Chinese rhesus macaques (Ch-RM) than in In-RM, we evaluated cART administration to SIVmac-infected Ch-RM as a potential model for studies of residual virus and eradication strategies. Four SIVmac239-infected Ch-RM received cART including reverse transcriptase inhibitors PMPA/FTC and integrase inhibitor L-870812 daily for 8 weeks. Plasma viral loads were promptly reduced to < 30 copies/ml upon initiation of cART. Cell-associated SIV DNA levels in lymphocytes from the gut were also significantly reduced. Jejunal and colonic CCR5 + CD4 + mucosal memory T cells increased significantly; restoration of these cells was associated with reductions in immune activation. In conclusion, cART effectively suppressed viral replication to < 30 vRNA copies/ml in SIVmac239-infected Ch-RM, reducing immune activation and restoring mucosal immune cell populations. SIVmac239-infected Ch-RM may be a useful model for studying responses to cART and persistent tissue reservoirs and evaluating candidate eradication strategies to cure HIV infection.

Vaccine-induced plasmablast responses in rhesus macaques: Phenotypic characterization and a source for generating antigen-specific monoclonal antibodies

“…Rhesus macaques have emerged as a major model for studies of HIV (or SIV and SHIV) pathogenesis, evaluation of novel therapeutics or antivirals, as well as for vaccine development (Hansen et al, 2013; Ling et al, 2013; Zhou et al, 2013; Roederer et al, 2014). In addition, this model is widely used to investigate many other human pathogens as well as the efficacy of new vaccine candidates (reviewed by (Gujer et al, 2011)).…”

Major Histocompatibility Complex Class I Haplotype Diversity in Chinese Rhesus Macaques

“…to study infectious diseases including simian immunodeficiency virus/ human immunodeficiency virus, avian influenza, malaria, plague, and severe acute respiratory syndrome, as well as studies of xenotransplantation, stem cell therapies, reproduction, and neurobiology (Shen et al 2007;Chen et al 2009Chen et al , 2011Chen et al , 2012Choi et al 2011;Liu et al 2011;Tian et al 2011;Wei et al 2011;Hutnick et al 2012;Li et al 2012b;Ling et al 2013;Mumbauer et al 2013). Yet comparatively little is known about the immunogenetics of these animals.…”

Aikeqing decreases viral loads in SHIV89.6-infected Chinese rhesus macaques

“…Mothé et al [ 11 ] reported Ch-RM MHC immunogenetics are more similar to HLA than those of Indian macaques, and therefore that Ch-RMs might be a better model for HIV. The SIV-infected Ch-RM has been successfully used as a model for studying responses to combination antiretroviral therapy (ART) and evaluating candidate eradication strategies to cure HIV infection [ 12 ]. Our study was performed to develop a chronically SHIV89.6-infected Ch-RM model for detailed investigation of Chinese medicine therapeutic effects.…”