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 (< 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.
Goicoechea
Miguel
M
Department of Medicine, University of California, San Diego, Antiviral Antiviral Research Center, 92131 . mgoicoechea@ucsd.edu
Smith
Davey M
DM
Liu
Lin
L
May
Susanne
S
Tenorio
Allan R
AR
Ignacio
Caroline C
CC
Landay
Alan
A
Haubrich
Richard
R
D000328:Adult; D000367:Age Factors; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D015331:Cohort Studies; D004279:DNA, Viral / Q000097:blood; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D007963:Leukocytes, Mononuclear / Q000821:virology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D012307:Risk Factors
D044966:Anti-Retroviral Agents; D004279:DNA, Viral