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
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Persaud, D.
Right arrow Articles by Siliciano, R. F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Persaud, D.
Right arrow Articles by Siliciano, R. F.

 Previous Article  |  Next Article 

Journal of Virology, January 2004, p. 968-979, Vol. 78, No. 2
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.2.968-979.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Continued Production of Drug-Sensitive Human Immunodeficiency Virus Type 1 in Children on Combination Antiretroviral Therapy Who Have Undetectable Viral Loads

Deborah Persaud,1* George K. Siberry,1 Aima Ahonkhai,2 Joleen Kajdas,1 Daphne Monie,2 Nancy Hutton,1 Douglas C. Watson,3 Thomas C. Quinn,2,4 Stuart C. Ray,2 and Robert F. Siliciano2,5

Department of Pediatrics,1 Department of Medicine, Johns Hopkins University School of Medicine,2 Department of Pediatrics, University of Maryland School of Medicine,3 Howard Hughes Medical Institute, Baltimore,5 National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland4

Received 11 July 2003/ Accepted 3 October 2003

Highly active antiretroviral therapy (HAART) can suppress plasma human immunodeficiency virus type 1 (HIV-1) levels to below the detection limit of ultrasensitive clinical assays. However, HIV-1 persists in cellular reservoirs, and in adults, persistent low-level viremia is detected with more sensitive assays. The nature of this viremia is poorly understood, and it is unclear whether viremia persists in children on HAART, particularly those who start therapy shortly after birth. We therefore developed a reverse transcriptase PCR (RT-PCR) assay that allows genotyping of HIV-1 protease even when viremia is present at levels as low as 5 copies of HIV-1 RNA/ml. We demonstrated that viremia persists in children with plasma virus levels below the limit of detection of clinical assays. Viremia was detected even in children who began HAART in early infancy and maintained such strong suppression of viremia that HIV-1-specific antibody responses were absent or minimal. The low-level plasma virus lacked protease inhibitor resistance mutations despite the frequent use of nelfinavir, which has a low mutational barrier to resistance. Protease sequences resembled those of viruses in the latent reservoir in resting CD4+ T cells. Thus, in most children on HAART with clinically undetectable viremia, there is continued virus production without evolution of resistance in the protease gene.

* Corresponding author. Mailing address: Department of Pediatrics, Johns Hopkins University School of Medicine, Park 256, 600 North Wolfe St., Baltimore, MD 21205. Phone: (410) 614-3917. Fax: (410) 614-1491. E-mail: dpers{at}jhmi.edu.

Journal of Virology, January 2004, p. 968-979, Vol. 78, No. 2
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.2.968-979.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Dinoso, J. B., Kim, S. Y., Wiegand, A. M., Palmer, S. E., Gange, S. J., Cranmer, L., O'Shea, A., Callender, M., Spivak, A., Brennan, T., Kearney, M. F., Proschan, M. A., Mican, J. M., Rehm, C. A., Coffin, J. M., Mellors, J. W., Siliciano, R. F., Maldarelli, F. (2009). Treatment intensification does not reduce residual HIV-1 viremia in patients on highly active antiretroviral therapy. Proc. Natl. Acad. Sci. USA 106: 9403-9408 [Abstract] [Full Text]  
  • Bailey, J. R., Sedaghat, A. R., Kieffer, T., Brennan, T., Lee, P. K., Wind-Rotolo, M., Haggerty, C. M., Kamireddi, A. R., Liu, Y., Lee, J., Persaud, D., Gallant, J. E., Cofrancesco, J. Jr., Quinn, T. C., Wilke, C. O., Ray, S. C., Siliciano, J. D., Nettles, R. E., Siliciano, R. F. (2006). Residual Human Immunodeficiency Virus Type 1 Viremia in Some Patients on Antiretroviral Therapy Is Dominated by a Small Number of Invariant Clones Rarely Found in Circulating CD4+ T Cells.. J. Virol. 80: 6441-6457 [Abstract] [Full Text]  
  • Tobin, N. H., Learn, G. H., Holte, S. E., Wang, Y., Melvin, A. J., McKernan, J. L., Pawluk, D. M., Mohan, K. M., Lewis, P. F., Mullins, J. I., Frenkel, L. M. (2005). Evidence that Low-Level Viremias during Effective Highly Active Antiretroviral Therapy Result from Two Processes: Expression of Archival Virus and Replication of Virus. J. Virol. 79: 9625-9634 [Abstract] [Full Text]  
  • Monie, D., Simmons, R. P., Nettles, R. E., Kieffer, T. L., Zhou, Y., Zhang, H., Karmon, S., Ingersoll, R., Chadwick, K., Zhang, H., Margolick, J. B., Quinn, T. C., Ray, S. C., Wind-Rotolo, M., Miller, M., Persaud, D., Siliciano, R. F. (2005). A Novel Assay Allows Genotyping of the Latent Reservoir for Human Immunodeficiency Virus Type 1 in the Resting CD4+ T Cells of Viremic Patients. J. Virol. 79: 5185-5202 [Abstract] [Full Text]  
  • Nettles, R. E., Kieffer, T. L., Kwon, P., Monie, D., Han, Y., Parsons, T., Cofrancesco, J. Jr, Gallant, J. E., Quinn, T. C., Jackson, B., Flexner, C., Carson, K., Ray, S., Persaud, D., Siliciano, R. F. (2005). Intermittent HIV-1 Viremia (Blips) and Drug Resistance in Patients Receiving HAART. JAMA 293: 817-829 [Abstract] [Full Text]  


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