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/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.