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1 July 2006

Volume 194, Number 1
The Journal of Infectious Diseases 2006;194:29–37
© 2006 by the Infectious Diseases Society of America. All rights reserved.
0022-1899/2006/19401-0006$15.00
DOI: 10.1086/504718
MAJOR ARTICLE

Determinants of CD4+ T Cell Recovery during Suppressive Antiretroviral Therapy: Association of Immune Activation, T Cell Maturation Markers, and Cellular HIV‐1 DNA

Miguel Goicoechea,1

Davey M. Smith,1

Lin Liu,2

Susanne May,2

Allan R. Tenorio,3

Caroline C. Ignacio,1

Alan Landay,3,4 and

Richard Haubrich1

1Department of Medicine and 2Division of Biostatistics and Bioinformatics, Department of Family and Preventive Medicine, University of California, San Diego; Departments of 3Medicine and 4Immunology and Microbiology, Rush Medical College, Chicago, Illinois

Background.Suboptimal CD4+ T cell recovery during antiretroviral therapy (ART) is a common clinical dilemma.

Methods.We analyzed viral and immunologic predictors of CD4+ T cell recovery in 116 human immunodeficiency virus type 1 (HIV‐1)–infected subjects who had suppressed viremia (50 copies/mL) while receiving ART. Successive measurements of T cell immunophenotypes and cellular HIV‐1 DNA levels were obtained before and during receipt of ART. On the basis of increases in the CD4+ T cell count, subjects were classified as immunologically concordant (demonstrating an increase of 100 CD4+ T cells/mm3) or discordant (demonstrating an increase of <100 CD4+ T cells/mm3) after 48 weeks of ART.

Results.In adjusted analyses, CD4+ and CD8+ T cell activation at baseline was negatively associated with immunologic concordance at week 48 of ART (odds ratio [OR], 0.80 [ ] and 0.67 [ ], respectively). High memory (CDRA−CD62L−) CD8+ T cell counts at baseline (OR, 0.33 [ ]) predicted less CD4+ T cell recovery, whereas increased naive CD4+ T cell counts were associated with higher increases in CD4+ T cells (OR, 1.19 [ ]). Neither the cell‐associated HIV‐1 DNA level at baseline ( ) nor the cell‐associated HIV‐1 DNA level at week 48 of ART ( ) was associated with immunologic concordance during ART.

Conclusions.These results support the potential clinical usefulness of the baseline determination of immune activation and maturation subsets in the prediction of CD4+ T cell recovery during viral suppression. Furthermore, identification of individuals with reduced potential for CD4+ T cell recovery during ART may provide a rationale for the initiation of early therapy for some patients.

Received 14 December 2005; accepted 23 February 2006; electronically published 18 May 2006.

Reprints or correspondence: Dr. Miguel Goicoechea, University of California, San Diego, Antiviral Research Center, 150 W. Washington St., Ste. 100, San Diego, CA 92131 ().

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  • Presented in part: XVth International AIDS Conference, Bangkok, Thailand, 11–17 July 2004 (abstract MoPeA3079).

    Potential conflicts of interest: none reported.

    Financial support: California Collaborative Treatment Group University‐wide AIDS Research Program (grant CC02‐SD‐003); the Adult AIDS Clinical Trials Group (AACTG) funded by the National Institutes of Allergy and Infectious Diseases (grants 5K23 AI055276, AI27670, and AI043638); the AACTG Central Group (grant U01AI38858); University of California San Diego Center for AIDS Research (grant SP30 AI36214); National Institutes of Health Center of Health (grants AI29164, AI047745, and AI07384); Research Center for AIDS and HIV Infection of the San Diego Veterans Affairs Healthcare System; Pfizer Pharmaceuticals.

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