title: 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.
authors: 1 Tulane National Primate Research Center , Covington, Louisiana.
authors: Binhua
authors: B
authors: Ling
authors: Linda
authors: L
authors: Rogers
authors: Ann-Marie
authors: AM
authors: Johnson
authors: Michael
authors: M
authors: Piatak
authors: Jeffrey
authors: J
authors: Lifson
authors: Ronald S
authors: RS
authors: Veazey
mesh_terms: D000818:Animals; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D004279:DNA, Viral / Q000097:blood; D004195:Disease Models, Animal; D008253:Macaca mulatta; D012367:RNA, Viral / Q000097:blood; D016097:Simian Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000302:isolation & purification; D019562:Viral Load
chemical_list: D004279:DNA, Viral; D012367:RNA, Viral
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