Determinants of CD4+ T Cell Recovery during Suppressive Antiretroviral Therapy: Association of Immune Activation, T Cell Maturation Markers, and Cellular HIV-1 DNA
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.
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Online publication date: 1-Nov-2008.
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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.