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15 June 2006

Volume 193, Number 12
The Journal of Infectious Diseases 2006;193:1718–1727
© 2006 by the Infectious Diseases Society of America. All rights reserved.
0022-1899/2006/19312-0015$15.00
DOI: 10.1086/504264
MAJOR ARTICLE

Long‐Term Decay of the HIV‐1 Reservoir in HIV‐1–Infected Children Treated with Highly Active Antiretroviral Therapy

Marisa Zanchetta,1

Sarah Walker,3

Nicoletta Burighel,1

Domenico Bellanova,1

Osvalda Rampon,2

Carlo Giaquinto,2 and

Anita De Rossi1

1Department of Oncology and Surgical Sciences, Unit of Viral Oncology, AIDS Reference Center, and 2Department of Pediatrics, University of Padova, Padova, Italy; 3Medical Research Centre Clinical Trials Unit, London, United Kingdom

To investigate the decay of the human immunodeficiency virus type 1 (HIV‐1) reservoir in children receiving highly active antiretroviral therapy (HAART), we measured HIV‐1 DNA in peripheral blood mononuclear cells from 14 children who achieved and maintained suppression of plasma viremia up to 48 months after the initiation of HAART. Levels of intracellular unspliced and multiply spliced HIV‐1 RNA were used as markers of residual viral replication. During the first month of HAART, there were significant decays in levels of both plasma HIV‐1 RNA and multiply spliced HIV‐1 RNA, yet unspliced HIV‐1 RNA persisted in most of the children. Greater HIV‐1 DNA decay during the first month of HAART correlated with a higher concomitant increase in CD4+ cell counts ( ) and a smaller subsequent HIV‐1 DNA decay ( ). Furthermore, HIV‐1 DNA decayed faster from 1 to 9 months of HAART (median half‐life, 5 months) than during the subsequent follow‐up period (median half‐life, 30 months). Moreover, after 9 months of HAART, HIV‐1 DNA tended to decay more slowly in children with detectable levels of unspliced HIV‐1 RNA. These findings suggest that clearance of the viral reservoir in HAART‐treated children may be influenced by immune repopulation and residual viral replication and may help in refining long‐term treatment strategies.

Received 28 September 2005; accepted 25 January 2006; electronically published 10 May 2006.

Reprints or correspondence: Dr. Anita De Rossi, Dept. of Oncology and Surgical Sciences, Sect. of Oncology, AIDS Reference Center, Via Gattamelata 64, 35128, Padova, Italy ().

Cited by

Hans S L M Nottet, Sabine J van Dijk, Ewout B Fanoy, Irma W Goedegebuure, Dorien de Jong, Nienke Vrisekoop, Debbie van Baarle, Valerie Boltz, Sarah Palmer, Jan C C Borleffs, Charles A B Boucher. (2009) HIV-1 Can Persist in Aged Memory CD4+ T Lymphocytes With Minimal Signs of Evolution After 8.3 Years of Effective Highly Active Antiretroviral Therapy. JAIDS Journal of Acquired Immune Deficiency Syndromes 50:4, 345-353
Online publication date: 1-May-2009.
CrossRef
Elisa Antonielli d’Oulx, Elena Chiappini, Maurizio Martino, Pier-Angelo Tovo. (2007) Treatment of pediatric HIV infection. Current Infectious Disease Reports 9:5, 425-433
Online publication date: 1-Oct-2007.
CrossRef
Anita De Rossi. (2007) Virus???host interactions in paediatric HIV-1 infection. Current Opinion in HIV and AIDS 2:5, 399-404
Online publication date: 1-Oct-2007.
CrossRef

  • Potential conflicts of interest: none reported.

    Financial support: Istituto Superiore Sanitá, Progetto AIDS (grants 40F.31 and 45F.13).

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