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1 February 2005

Volume 191, Number 3
The Journal of Infectious Diseases 2005;191:348–357
© 2004 by the Infectious Diseases Society of America. All rights reserved.
0022-1899/2005/19103-0005$15.00
DOI: 10.1086/427340
MAJOR ARTICLE

Low‐Level Viremia and Proviral DNA Impede Immune Reconstitution in HIV‐1–Infected Patients Receiving Highly Active Antiretroviral Therapy

Sisse R. Ostrowski,1

Terese L. Katzenstein,1

Per T. Thim,1

Bente K. Pedersen,1,2

Jan Gerstoft,1 and

Henrik Ullum1,3

1Department of Infectious Diseases, 2Copenhagen Muscle Research Centre, and 3Department of Clinical Immunology, Rigshospitalet, Copenhagen, Denmark

Background.Immunological and virological consequences of low‐level viremia in human immunodeficiency virus (HIV) type 1–infected patients receiving highly active antiretroviral therapy (HAART) remain to be determined.

Methods.For 24 months, 101 HAART‐treated, HIV‐1–infected patients with HIV RNA levels 200 copies/mL were followed prospectively: HIV RNA level and CD4 and CD8 cell counts were investigated every 3 months, and proviral DNA and T cell subsets were investigated every 6 months.

Results.During follow‐up, 33 patients had HIV RNA levels 20 copies/mL at all visits (uVL patients), whereas 68 patients had HIV RNA levels >20 copies/mL at 1 visit (dVL patients) (median increase, 81 copies/mL [interquartile range, 37–480 copies/mL]). dVL patients had higher concentrations of CD8 cells, activated and memory T cells, and proviral DNA, compared with uVL patients ( ). A higher HIV RNA level was independently associated with reduced CD4 gain ( ). A higher HIV RNA level also was associated with increases in activated CD8+CD38+ and CD8+HLA‐DR+ cells ( ), and a higher level of activated CD8+CD38+ cells was independently associated with reduced CD4 gain ( ). A higher proviral DNA level was associated with increases in CD4+CD45RA−CD28− effector cells and reductions in naive CD4+CD45RA+CD62L+ and CD8+CD45RA+CD62L+ cells ( ). Higher levels of activated CD4+HLA‐DR+ and early differentiated CD4+CD45RA−CD28+ cells predicted increased risk of subsequent detectable viremia in patients with undetectable HIV RNA ( ).

Conclusion.These findings indicate that low‐level viremia and proviral DNA are intimately associated with the immunological and virological equilibrium in patients receiving HAART.

Received 25 April 2004; accepted 8 July 2004; electronically published 30 December 2004.

Reprints or correspondence: Dr. Sisse R. Ostrowski, Rigshospitalet, Dept. of Infectious Diseases, M7641, Blegdamsvej 9, DK‐2100 Copenhagen, Denmark ().

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  • Presented in part: First International Workshop on HIV Persistence during Therapy, St. Martin, French West Indies, 10–12 December 2003 (abstract PP4.9).

    Financial support: Danish AIDS Foundation.

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