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Journal of Virology, February 2000, p. 1704-1711, Vol. 74, No. 4
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Antiretroviral Therapy during Primary Immunodeficiency Virus Infection Can Induce Persistent Suppression of Virus Load and Protection from Heterologous Challenge in Rhesus Macaques

Brigitte Rosenwirth,1 Peter ten Haaft,1 Willy M. J. M. Bogers,1 Ivonne G. Nieuwenhuis,1 Henk Niphuis,1 Eva-Maria Kuhn,1 Norbert Bischofberger,2 Jonathan L. Heeney,1 and Klaus Überla3,*

Departments of Virology and Animal Science, Biomedical Primate Research Center, 2288 GJ Rijswijk, The Netherlands1; Gilead Sciences Inc., Foster City, California 944042; and Institute of Virology, University of Leipzig, D-04103 Leipzig, Germany3

Received 29 July 1999/Accepted 22 November 1999

A limited period of chemotherapy during primary immunodeficiency virus infection might provide a long-term clinical benefit even if treatment is initiated at a time point when virus is already detectable in plasma. To evaluate this strategy, we infected rhesus macaques with the pathogenic simian/human immunodeficiency virus RT-SHIV and treated them with the antiretroviral drug (R)-9-(2-phosphonylmethoxypropyl)adenine (PMPA) for 8 weeks starting 7 or 14 days postinfection. PMPA treatment suppressed viral replication efficiently in all of the monkeys. After chemotherapy ended, virus replication rebounded and viral RNA in plasma reached levels comparable to that of the controls in four of the six monkeys. However, in the other two animals, virus loads peaked only moderately after withdrawal of the drug and then declined to low or even undetectable levels. These low levels of viremia remained stable for at least 31 weeks after cessation of therapy. At this time point, these two monkeys were challenged with SIV8980 to evaluate whether the host responses which were able to keep RT-SHIV replication under control were also sufficient to protect against infection with a highly pathogenic heterologous virus. Both monkeys proved to be protected against the heterologous virus. In one of the two animals, low levels of SIV8980 replication were detected. Thus, by chemotherapy during the acute phase of pathogenic virus replication, we could achieve not only persistent virus load suppression in two out of six monkeys but also protection from subsequent heterologous challenge. By this chemotherapeutic attenuation, the replication kinetics of attenuated viruses could be mimicked and a vaccination effect similar to that induced by live attenuated simian immunodeficiency virus vaccines was achieved.

* Corresponding author. Mailing address: Institute of Virology, University of Leipzig, Liebigstr. 24, D-04103 Leipzig, Germany. Phone: 49 341 9714314. Fax: 49 341 9714309. E-mail: ueberla{at}medizin.uni-leipzig.de.

Journal of Virology, February 2000, p. 1704-1711, Vol. 74, No. 4
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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