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Journal of Virology, March 2000, p. 2584-2593, Vol. 74, No. 6
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Containment of Simian Immunodeficiency Virus Infection: Cellular
Immune Responses and Protection from Rechallenge following Transient
Postinoculation Antiretroviral Treatment
Jeffrey D.
Lifson,1,*
Jeffrey L.
Rossio,1
Ramy
Arnaout,2
Li
Li,1
Thomas L.
Parks,1
Douglas K.
Schneider,1
Rebecca F.
Kiser,1
Vicky J.
Coalter,1
Geneva
Walsh,1
Robert J.
Imming,1
Bradley
Fisher,3
Bernard M.
Flynn,3
Norbert
Bischofberger,4
Michael
Piatak Jr.,1
Vanessa M.
Hirsch,5
Martin A.
Nowak,2 and
Dominik
Wodarz2
AIDS Vaccine Program, SAIC Frederick, National Cancer
Institute-Frederick Cancer Research and Development Center,
Frederick, Maryland 217021; Program in
Theoretical Biology, Institute for Advanced Study, Princeton, New
Jersey 085402; Animal Sciences
Branch, National Cancer Institute, Bethesda, Maryland
208923; Gilead Sciences, Inc.,
Foster City, California 944044; and
Laboratory of Molecular Microbiology, National Institute of
Allergy and Infectious Diseases, Rockville, Maryland
208525
Received 20 August 1999/Accepted 23 December 1999
To better understand the viral and host factors involved in the
establishment of persistent productive infection by primate lentiviruses, we varied the time of initiation and duration of postinoculation antiretroviral treatment with tenofovir
{9-[2-(R)-(phosphonomethoxy)propyl]adenine}while performing intensive virologic and immunologic monitoring in
rhesus macaques, inoculated intravenously with simian immunodeficiency virus SIVsmE660. Postinoculation treatment did not block the initial infection, but we identified treatment regimens that prevented the
establishment of persistent productive infection, as judged by the
absence of measurable plasma viremia following drug
discontinuation. While immune responses were heterogeneous,
animals in which treatment resulted in prevention of
persistent productive infection showed a higher frequency and higher
levels of SIV-specific lymphocyte proliferative responses during the
treatment period compared to control animals, despite the absence of
either detectable plasma viremia or seroconversion. Animals protected
from the initial establishment of persistent productive infection were
also relatively or completely protected from subsequent homologous
rechallenge. Even postinoculation treatment regimens that did not
prevent establishment of persistent infection resulted in
downmodulation of the level of plasma viremia following treatment
cessation, compared to the viremia seen in untreated control
animals, animals treated with regimens known to be ineffective, or the
cumulative experience with the natural history of plasma viremia
following infection with SIVsmE660. The results suggest that the host
may be able to effectively control SIV infection if the initial
exposure occurs under favorable conditions of low viral burden and in
the absence of ongoing high level cytopathic infection of responding
cells. These findings may be particularly important in relation to
prospects for control of primate lentiviruses in the settings of both
prophylactic and therapeutic vaccination for prevention of AIDS.
*
Corresponding author. Mailing address: Retroviral
Pathogenesis Laboratory, AIDS Vaccine Program, SAIC Frederick, National Cancer Institute-Frederick Cancer Research and Development Center, Building 535, Fifth Floor, Frederick, MD 21702. Phone: (301) 846-1408. Fax: (301) 846-5588. E-mail: lifson{at}avpaxp1.ncifcrf.gov.
Journal of Virology, March 2000, p. 2584-2593, Vol. 74, No. 6
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
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