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Journal of Virology, January 2009, p. 329-335, Vol. 83, No. 1
0022-538X/09/$08.00+0     doi:10.1128/JVI.01763-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Evidence for Persistent Low-Level Viremia in Individuals Who Control Human Immunodeficiency Virus in the Absence of Antiretroviral Therapy{triangledown}

Hiroyu Hatano,1* Eric L. Delwart,1,2 Philip J. Norris,1,2 Tzong-Hae Lee,2 Joan Dunn-Williams,2 Peter W. Hunt,1 Rebecca Hoh,1 Susan L. Stramer,3 Jeffrey M. Linnen,4 Joseph M. McCune,1 Jeffrey N. Martin,1 Michael P. Busch,1,5 and Steven G. Deeks1

Department of Medicine, University of California, San Francisco, California,1 Blood Systems Research Institute, San Francisco, California,2 American Red Cross, Gaithersburg, Maryland,3 Gen-Probe Inc., San Diego, California,4 Department of Laboratory Medicine, University of California, San Francisco, California5

Received 20 August 2008/ Accepted 13 October 2008

A subset of antiretroviral-untreated, human immunodeficiency virus (HIV)-infected individuals are able to maintain undetectable plasma HIV RNA levels in the absence of antiretroviral therapy. These "elite" controllers are of high interest as they may provide novel insights regarding host mechanisms of virus control. The degree to which these individuals have residual plasma viremia has not been well defined. We performed a longitudinal study of 46 elite controllers, defined as HIV-seropositive, antiretroviral-untreated individuals with plasma HIV RNA levels of <50 to 75 copies/ml. The median duration of HIV diagnosis was 13 years, the median baseline CD4+ T-cell count was 753 cells/mm3, and the median duration of follow-up was 16 months. Plasma and cellular HIV RNA levels were measured using the transcription-mediated amplification (TMA) assay (estimated limit of detection of <3.5 copies RNA/ml). A total of 1,117 TMA assays were performed (median of five time points/subject and four replicates/time point). All but one subject had detectable plasma HIV RNA on at least one time point, and 15 (33%) subjects had detectable RNA at all time points. The majority of controllers also had detectable cell-associated RNA and proviral DNA. A mixed-effect linear model showed no strong evidence of change in plasma RNA levels over time. In conclusion, the vast majority (98%) of elite controllers had measurable plasma HIV RNA, often at levels higher than that observed in antiretroviral-treated patients. This confirms the failure to eradicate the virus, even in these unique individuals who are able to reduce plasma viremia to very low levels without antiretroviral therapy.

* Corresponding author. Mailing address: San Francisco General Hospital, Building 80, Ward 84, 995 Potrero Avenue, San Francisco, CA 94110. Phone: (415) 476-4082, ext. 122. Fax: (415) 476-6953. E-mail: hhatano{at}php.ucsf.edu

{triangledown} Published ahead of print on 22 October 2008.

Journal of Virology, January 2009, p. 329-335, Vol. 83, No. 1
0022-538X/09/$08.00+0     doi:10.1128/JVI.01763-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Saez-Cirion, A., Sinet, M., Shin, S. Y., Urrutia, A., Versmisse, P., Lacabaratz, C., Boufassa, F., Avettand-Fenoel, V., Rouzioux, C., Delfraissy, J.-F., Barre-Sinoussi, F., Lambotte, O., Venet, A., Pancino, G., for the ANRS EP36 HIV Controllers Study Group, (2009). Heterogeneity in HIV Suppression by CD8 T Cells from HIV Controllers: Association with Gag-Specific CD8 T Cell Responses. J. Immunol. 182: 7828-7837 [Abstract] [Full Text]  


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