This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Google Scholar
Right arrow Articles by Kubo, M.
Right arrow Articles by Martin, M. A.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kubo, M.
Right arrow Articles by Martin, M. A.

 Previous Article  |  Next Article 

Journal of Virology, July 2009, p. 7099-7108, Vol. 83, No. 14
0022-538X/09/$08.00+0     doi:10.1128/JVI.02522-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Initiation of Antiretroviral Therapy 48 Hours after Infection with Simian Immunodeficiency Virus Potently Suppresses Acute-Phase Viremia and Blocks the Massive Loss of Memory CD4+ T Cells but Fails To Prevent Disease{triangledown}

Makoto Kubo,{dagger} Yoshiaki Nishimura, Masashi Shingai, Wendy Lee, Jason Brenchley, Bernard Lafont, Alicia Buckler-White, Tatsuhiko Igarashi, and Malcolm A. Martin*

Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892

Received 8 December 2008/ Accepted 29 April 2009

We investigated whether a 28-day course of potent antiretroviral therapy, initiated at a time point (48 h postinoculation) following simian immunodeficiency virus (SIV) inoculation when the acquisition of a viral infection was virtually assured, would sufficiently sensitize the immune system and result in controlled virus replication when treatment was stopped. The administration of tenofovir 48 h after SIV inoculation to six Mamu-A*01-negative rhesus macaques did, in fact, potently suppress virus replication in all of the treated rhesus macaques, but plasma viral RNA rapidly became detectable in all six animals following its cessation. Unexpectedly, the viral set points in the treated monkeys became established at two distinct levels. Three controller macaques had chronic phase virus loads in the range of 1 x 103 RNA copies/ml, whereas three noncontroller animals had set points of 2 x 105 to 8 x 105 RNA copies/ml. All of the noncontroller monkeys died with symptoms of immunodeficiency by week 60 postinfection, whereas two of the three controller animals were alive at week 80. Interestingly, the three controller macaques each carried major histocompatibility complex class I alleles that previously were reported to confer protection against SIV, and two of these animals generated cytotoxic T-lymphocyte escape viral variants during the course of their infections.

* Corresponding author. Mailing address: Bldg. 4, Rm. 315A, 4 Center Dr. MSC 0460, National Institutes of Health, Bethesda, MD 20892-0460. Phone: (301) 496-4012. Fax: (301) 402-0226. E-mail: malm{at}nih.gov

{triangledown} Published ahead of print on 6 May 2009.

{dagger} Present address: Division of Immunology, Kitasato University of Allied Health Sciences, 1-15-1 Kitasata Sagamihara, Kanagawa 228-8555, Japan.

Journal of Virology, July 2009, p. 7099-7108, Vol. 83, No. 14
0022-538X/09/$08.00+0     doi:10.1128/JVI.02522-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»