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

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/mm(3)) or discordant (demonstrating an increase of < 100 CD4(+) T cells/mm(3)) 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=0.2], respectively). High memory (CDRA(-)CD62L(-)) CD8(+) T cell counts at baseline (OR, 0.33 [P=.05]) predicted less CD4(+) T cell Pp. 05 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.