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

Goicoechea, Miguel; Smith, Davey M.; Lin Liu; May, Susanne; Tenorio, Allan R.; Ignacio, Caroline C.; Landay, Alan; Haubrich, Richard
July 2006
Journal of Infectious Diseases;7/1/2006, Vol. 194 Issue 1, p29
Academic Journal
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 [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.


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