Incomplete reconstitution of T cell subsets on combination antiretroviral therapy in the AIDS Clinical Trials Group protocol 384

Clin Infect Dis. 2009 Feb 1;48(3):350-61. doi: 10.1086/595888.


Background: Initiation of combination antiretroviral therapy (ART) results in higher total CD4 cell counts, a surrogate for immune reconstitution. Whether the baseline CD4 cell count affects reconstitution of immune cell subsets has not been well characterized.

Methods: Using data from 978 patients (621 with comprehensive immunological assessments) from the AIDS [Acquired Immunodeficiency Syndrome] Clinical Trials Group protocol 384, a randomized trial of initial ART, we compared reconstitution of CD4(+), CD4(+) naive and memory, CD4(+) activation, CD8(+), CD8(+) activation, B, and natural killer cells among patients in different baseline CD4(+) strata. Reference ranges for T cell populations in control patients negative for human immunodeficiency virus (HIV) infection were calculated using data from AIDS Clinical Trials Group protocol A5113.

Results: Patients in the lower baseline CD4(+) strata did not achieve total CD4(+) cell counts similar to those of patients in the higher strata during 144 weeks of ART, although CD4(+) cell count increases were similar. Ratios of CD4(+) naive-memory cell counts and CD4(+):CD8(+) cell counts remained significantly reduced in patients with lower baseline CD4(+) cell counts (<or=350 cells/mm(3)). These immune imbalances were most notable for those initiating ART with a baseline CD4(+) cell count <or=200 cells/mm(3), even after adjustment for baseline plasma HIV RNA levels.

Conclusions: After nearly 3 years of ART, T cell subsets in patients with baseline CD4(+) cell counts >350 cells/mm(3) achieved or approached the reference range those of control individuals without HIV infection. In contrast, patients who began ART with <or=350 CD4(+) cells/mm(3) generally did not regain normal CD4(+) naive-memory cell ratios. These results support current guidelines to start ART at a threshold of 350 cells/mm(3) and suggest that there may be immunological benefits associated with initiating therapy at even higher CD4(+) cell counts.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Acquired Immunodeficiency Syndrome / drug therapy*
  • Acquired Immunodeficiency Syndrome / immunology*
  • Adult
  • Antiretroviral Therapy, Highly Active*
  • B-Lymphocytes / immunology
  • CD4 Lymphocyte Count
  • CD4-CD8 Ratio
  • Female
  • Humans
  • Killer Cells, Natural / immunology
  • Male
  • Middle Aged
  • T-Lymphocyte Subsets / immunology*