Parallel decline of CD8+/CD38++ T cells and viraemia in response to quadruple highly active antiretroviral therapy in primary HIV infection

AIDS. 2002 Mar 8;16(4):589-96. doi: 10.1097/00002030-200203080-00010.

Abstract

Objectives: To monitor changes in the numbers of CD8 lymphocytes expressing the activated CD38++ phenotype in peripheral blood samples from patients with primary HIV infection (PHI) treated with highly active antiretroviral therapy (HAART).

Methods: Zidovudine, lamivudine, abacavir and amprenavir were initiated during PHI as part of the Quest study. Absolute numbers of CD8+/CD38++ T cells were determined using three-colour flow cytometry, and plasma viral load (VL) was measured using the Roche Amplicor method.

Results: The median, pre-therapy CD8+/CD38++ T cell count was 461/mm(3)(interquartile range 216, 974) in 131 patients compared with normal control values of less than 20 cells/mm(3). Levels fell markedly in parallel with VL within the first 2 weeks of HAART initiation, to a median of 47 cells/mm(3) at 28 weeks (median 436 cell decline; P < 0.001). At that time, 80% of patients had a VL less than 50 copies/ml, and 16.3% of all patients had less than 20 CD8+/CD38++ T cells/mm(3). A continued decrease in CD8+/CD38++ T cell count occurred in 67.2% of patients whose VL was maintained below 50 copies/ml (median change from first to last value -18 cells/mm(3); P < 0.001).

Conclusion: After the initiation of HAART in PHI, CD8+/CD38++ lymphocytes declined rapidly in parallel with VL, and allowed for a normalization of CD8+/CD38++ T cell numbers in a subset of patients at week 28. Cell numbers continued to decline in patients who maintained VL below 50 copies/ml, indicating that the CD8+/CD38++ T cell count may represent a marker of residual viral replication when VL falls below detectable levels after HAART intervention.

MeSH terms

  • Adult
  • Anti-HIV Agents / therapeutic use*
  • Antigens, CD / immunology*
  • Antiretroviral Therapy, Highly Active
  • Biomarkers
  • CD48 Antigen
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / immunology*
  • Carbamates
  • Dideoxynucleosides / therapeutic use*
  • Female
  • Furans
  • HIV Infections / drug therapy*
  • HIV Infections / immunology
  • HIV Infections / virology
  • HIV Protease Inhibitors / therapeutic use*
  • HIV-1 / drug effects*
  • HIV-1 / immunology
  • Humans
  • Lamivudine / therapeutic use*
  • Lymphocyte Count
  • Male
  • Middle Aged
  • Reverse Transcriptase Inhibitors / therapeutic use*
  • Sulfonamides / therapeutic use*
  • T-Lymphocyte Subsets / cytology
  • T-Lymphocyte Subsets / immunology
  • Treatment Outcome
  • Viral Load
  • Viremia*
  • Zidovudine / therapeutic use*

Substances

  • Anti-HIV Agents
  • Antigens, CD
  • Biomarkers
  • CD48 Antigen
  • Carbamates
  • Dideoxynucleosides
  • Furans
  • HIV Protease Inhibitors
  • Reverse Transcriptase Inhibitors
  • Sulfonamides
  • Lamivudine
  • Zidovudine
  • amprenavir
  • abacavir