Background: The goal of antiretroviral therapy (ART) is to suppress virus replication to limit immune system damage. Some have proposed combining ART with immune therapies to boost antiviral immunity. For this to be successful, ART must not impair physiological immune function.
Methods: We studied the impact of ART (tenofovir and emtricitabine) on systemic and mucosal immunity in uninfected and simian immunodeficiency (SIV)–infected Chinese rhesus macaques. Subcutaneous ART was initiated 2 weeks after tonsillar inoculation with SIVmac239.
Results: There was no evidence of immune dysregulation as a result of ART in either infected or uninfected animals. Early virus-induced alterations in circulating immune cell populations (decreased central memory T cells and myeloid dendritic cells) were detected, but normalized shortly after ART initiation. ART-treated animals showed marginal SIV-specific T-cell responses during treatment, which increased after ART discontinuation. Elevated expression of CXCL10 in oral, rectal, and blood samples and APOBEC3G mRNA in oral and rectal tissues was observed during acute infection and was down regulated after starting ART. ART did not impact the ability of the animals to respond to tonsillar application of polyICLC with increased CXCL10 expression in oral fluids and CD80 expression on blood myeloid dendritic cells.
Conclusion: Early initiation of ART prevented virus-induced damage and did not impede mucosal or systemic immune functions.
*Center for Biomedical Research, HIV/AIDS Program, Population Council, New York, NY
†Oncovir, Washington, DC
‡AIDS and Cancer Virus Program, SAIC-Frederick, National Cancer Institute, Frederick, MD
§Aaron Diamond AIDS Research Center, Rockefeller University, New York, NY
‖Tulane National Primate Research Center, Tulane University, Covington, LA
Correspondence to: Melissa Robbiani, PhD, Center for Biomedical Research, HIV and AIDS Program, Population Council, 1230 York Avenue, New York, NY 10065 (e-mail: email@example.com).
Supported by the National Institutes of Health (NIH) National Institute of Dental and Craniofacial Research Grant DE018293 and in part with federal funds from the National Cancer Institute, NIH, under Contract No. HHSN261200800001E. Partial support was provided to the Tulane National Primate Research Center by base Grant RR000164 and NIH construction Grants 1G20RR016930-01, 1G20RR018397-01, 1G20RR019628-01, 1G20RR013466-01, 1G20RR019607-01, 1G20RR21381, 1G20RR22760, and 1CO6RR012112-01. M. Robbiani is a 2002 Elizabeth Glaser Scientist.
The authors have no conflicts of interest to declare. None of the material in this manuscript has been published or is under consideration elsewhere.
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Received March 15, 2012
Accepted June 25, 2012