Determinants of CD4+ T cell recovery during suppressive antiretroviral therapy: association of immune activation, T cell maturation markers, and cellular HIV-1 DNA.

TitleDeterminants of CD4+ T cell recovery during suppressive antiretroviral therapy: association of immune activation, T cell maturation markers, and cellular HIV-1 DNA.
Publication TypeJournal Article
Year of Publication2006
AuthorsGoicoechea M, Smith DM, Liu L, May S, Tenorio AR, Ignacio CC, Landay A, Haubrich R
JournalJ Infect Dis
Volume194
Issue1
Pagination29-37
Date Published2006 Jul 1
ISSN0022-1899
KeywordsAdult, Age Factors, Anti-Retroviral Agents, CD4 Lymphocyte Count, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Cohort Studies, DNA, Viral, Female, HIV Infections, HIV-1, Humans, Immunophenotyping, Leukocytes, Mononuclear, Male, Middle Aged, Multivariate Analysis, Predictive Value of Tests, Risk Factors
Abstract

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 (< or = 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 > or = 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 [P = .04] and 0.67 [P = .02], respectively). High memory (CDRA(-)CD62L-) CD8+ T cell counts at baseline (OR, 0.33 [P = .05]) 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 [P = .052]). Neither the cell-associated HIV-1 DNA level at baseline (P = .32) nor the cell-associated HIV-1 DNA level at week 48 of ART (P = .42) 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.

DOI10.1086/504718
Alternate JournalJ. Infect. Dis.
PubMed ID16741879
Grant List5K23 AI055276 / AI / NIAID NIH HHS / United States
AI043638 / AI / NIAID NIH HHS / United States
AI047745 / AI / NIAID NIH HHS / United States
AI07384 / AI / NIAID NIH HHS / United States
AI27670 / AI / NIAID NIH HHS / United States
AI29164 / AI / NIAID NIH HHS / United States
SP30 AI36214 / AI / NIAID NIH HHS / United States
U01AI38858 / AI / NIAID NIH HHS / United States