Journal Article

Incomplete Reconstitution of T Cell Subsets on Combination Antiretroviral Therapy in the AIDS Clinical Trials Group Protocol 384

Gregory K. Robbins, John G. Spritzler, Ellen S. Chan, David M. Asmuth, Rajesh T. Gandhi, Benigno A. Rodriguez, Gail Skowron, Paul R. Skolnik, Robert W. Shafer and Richard B. Pollard

in Clinical Infectious Diseases

Published on behalf of Infectious Diseases Society of America

Volume 48, issue 3, pages 350-361
Published in print February 2009 | ISSN: 1058-4838
Published online February 2009 | e-ISSN: 1537-6591 | DOI: http://dx.doi.org/10.1086/595888
Incomplete Reconstitution of T Cell Subsets on Combination Antiretroviral Therapy in the AIDS Clinical Trials Group Protocol 384

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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 (⩽350 cells/mm3). These immune imbalances were most notable for those initiating ART with a baseline CD4+ cell count ⩽200 cells/mm3, 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/mm3 achieved or approached the reference range those of control individuals without HIV infection. In contrast, patients who began ART with ⩽350 CD4+ cells/mm3 generally did not regain normal CD4+ naive-memory cell ratios. These results support current guidelines to start ART at a threshold of 350 cells/mm3 and suggest that there may be immunological benefits associated with initiating therapy at even higher CD4+ cell counts.

Journal Article.  5694 words.  Illustrated.

Subjects: Infectious Diseases ; Immunology ; Public Health and Epidemiology ; Microbiology

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