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A simian immunodeficiency virus macaque model of highly active antiretroviral treatment: viral latency in the periphery and the central nervous system

Clements, Janice Ea,b,c,d; Gama, Lucioa; Graham, David Ra,e; Mankowski, Joseph La,b,c; Zink, MCa,b,f

Current Opinion in HIV and AIDS: January 2011 - Volume 6 - Issue 1 - p 37–42
doi: 10.1097/COH.0b013e3283412413
HIV reservoirs: from pathogenesis to drug development: Edited by Robert F. Siliciano and Janet D. Siliciano

Purpose of review Here, simian immunodeficiency virus (SIV) macaque models are examined for their strengths in identifying in-vivo sites of HIV latency and persistent virus replication during highly active antiretroviral treatment (HAART). The best characterized HIV reservoir in HAART-treated persons is resting CD4+ T cells in blood, although residual virus also comes from other reservoirs. Nonhuman primate/SIV models of HAART have been developed to characterize potential HIV reservoirs, particularly the central nervous system (CNS) and stem cells in bone marrow, known and potential reservoirs of latent virus that are difficult to study in humans.

Recent findings Few SIV macaque models of HAART have examined plasma and cerebrospinal fluid virus decay, the number of resting CD4+ T cells harboring replication-competent latent SIV, HAART-treatment effect on the CNS, or residual viral replication or viral DNA levels in that tissue. Using a consistent, accelerated SIV macaque model, we characterized peripheral viral reservoirs, including those in the CNS, among HAART-treated macaques. The SIV model reproduces latency in memory CD4+ T cells throughout the body and indicates that the CNS contains a stable SIV DNA reservoir.

Summary An SIV macaque model of HAART recapitulating viral latency, particularly in the CNS, is required to study therapeutic approaches for a functional HIV cure.

aDepartment of Molecular and Comparative Pathobiology, USA

bDepartment of Pathology, USA

cDepartment of Neurology, USA

dDepartment of Molecular Biology and Genetics, USA

eDepartment of Medicine, Division of Cardiology, Johns Hopkins University School of Medicine, USA

fDepartment of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA

Correspondence to Janice E. Clements, 839 Broadway Research Building, 733 North Broadway, Baltimore, MD 21205, USA Tel: +1 410 955 9770; e-mail:

© 2011 Lippincott Williams & Wilkins, Inc.