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Journal of Virology, July 2000, p. 5747-5753, Vol. 74, No. 13
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Suppression of Acute Viremia by Short-Term Postexposure Prophylaxis of Simian/Human Immunodeficiency Virus SHIV-RT-Infected Monkeys with a Novel Reverse Transcriptase Inhibitor (GW420867) Allows for Development of Potent Antiviral Immune Responses Resulting in Efficient Containment of Infection

Kazuyasu Mori,1,2,* Yasuhiro Yasutomi,3 Shuzo Sawada,4 Francois Villinger,5 Kazushige Sugama,6 Brigitte Rosenwith,7 Jonathan L. Heeney,7 Klaus Überla,8 Shudo Yamazaki,1 Aftab A. Ansari,5 and Helga Rübsamen-Waigmann9,*

AIDS Research Center1 and Tsukuba Primate Center for Medical Sciences,2 National Institute of Infectious Diseases, Tokyo 162-8640, Department of Bioregulation, Mie University School of Medicine, Tsu 514-8507,3 Bayer Yakuhin, Osaka 532-0003,4 and Omtest Laboratory, Kyurin Corporation, Kitakyushu 806-0046,6 Japan; Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia 303225; Department of Virology, Biomedical Primate Research Center, 2288 GH Rijswijk, The Netherlands7; and Institut für Virologie, Universität Leipzig, D-04103 Leipzig,8 and Department of Virus Research, Pharma Research Center, Bayer AG, D-42096 Wuppertal,9 Germany

Received 19 January 2000/Accepted 3 April 2000

A nonnucleoside reverse transcriptase (RT) inhibitor, GW420867, was tested for postexposure prophylaxis (PEP) in rhesus macaques experimentally infected with 100 50% tissue culture infective doses of a chimeric simian/human immunodeficiency virus (SHIV) containing the RT gene of HIV-1 (SHIV-RT). Animals were either mock treated, or treated for 4 weeks starting at 8 or 24 h postinfection (p.i.) with GW420867. While such therapy led to undetectable plasma viremia in three of six monkeys, a transient plasma viremia was noted in the other three treated animals at 2 to 4 weeks following cessation of therapy. Following this transient viremia all drug-treated animals showed low or undetectable levels of plasma viremia up to the last sample examined at 90 weeks p.i. Despite low and/or undetectable viremia, virus-specific cytotoxic T lymphocyte and viral Env-specific proliferative responses were seen in the peripheral blood mononuclear cells of both mock- and drug-treated animals as early as 3 weeks p.i. Such virus-specific cellular responses, however, were better maintained in the drug-treated animals than the mock-treated animals. In contrast to the virus-specific cellular response, the magnitude and kinetics of virus specific humoral responses appeared to correlate with the detection of viremia. These data support the view that a short-term PEP with GW420867 permits the generation and maintenance of long-lasting virus-specific cell-mediated immune responses while markedly reducing viral loads to undetectable levels for a prolonged period of time (90 weeks) and leads to long-term disease protection. This model provides a unique means to define mechanisms and correlates of disease protection.

* Corresponding author. Mailing address for Kazuyasu Mori: Tsukuba Primate Center for Medical Sciences, National Institute for Infectious Diseases, 1 Hachimandai, Tsukuba 305-0843, Japan. Phone: 81-298-37-2121. Fax: 81-298-37-0218. E-mail: mori{at}nih.go.jp. Mailing address for Helga Rübsamen-Waigmann: Department of Virus Research PH-R AI Virology Pharma Research Centre, Bayer AG, Aprather Weg, Postfach 101709, D-42096 Wuppertal, Germany. Phone: 49-0202-36-4143. Fax: 49-202-36-4162. E-mail: HELGA.RUEBSAMEN-WAIGMANN.HR{at}bayer-ag.de.

Journal of Virology, July 2000, p. 5747-5753, Vol. 74, No. 13
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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