Immune modulatory effects of cyclooxygenase type 2 inhibitors in HIV patients on combination antiretroviral treatment

AIDS. 2006 Apr 4;20(6):813-20. doi: 10.1097/01.aids.0000218544.54586.f1.

Abstract

Objectives: To examine the immune modulating effects of cyclooxygenase type 2 (COX-2) inhibitors (COX-2i) in HIV-infected patients on combination antiretroviral treatment (CART).

Design: In-depth substudy from an approved, open, controlled, randomized study comparing the immune modulating effects of CART in combination with COX-2i after 12 weeks.

Methods: Patients (n = 38) on long-term CART with stable viral load (VL) < 50,000 copies/ml and CD4+ T-cell counts > 100/microl were randomized to CART and rofecoxib 25 mg bid (n = 12) or celecoxib 400 mg bid (n = 12), or CART only without placebo (n = 14). Routine clinical chemistry, CD4+ and CD8+ counts and VL were safety parameters. Immunological parameters included C-reactive protein, beta2-microglobulin, Ig isotypes and IgG subclasses as well as several T-lymphocyte subsets. Non-parametric analyses were used throughout.

Results: Prestudy experiments showed higher median intracellular expression of COX-2 in CD4+ (P = 0.048) and possibly CD8+ (P = 0.09) T cells from patients on CART compared with uninfected controls. In the clinical study, increased CD4+ T-cell counts were observed only in patients on COX-2i with VL < 50 copies/ml (P = 0.02). Decreased expression of CD38+ on CD8+ T cells and subsets as well as reductions in IgA and IgM (P < 0.03) were most pronounced in patients on COX-2i who had detectable VL (n = 6). COX-2i treatment enhanced the perforin content particularly in the differentiated CD27-/CD8+ T-cell subsets compared with controls (P = 0.05).

Conclusions: COX-2i together with CART improved markers for persistent immune activation, particularly in patients with viraemia, as well as enhanced perforin expression, and thereby strengthened COX-2 as a potential therapeutic target in HIV infection.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADP-ribosyl Cyclase 1 / blood
  • Adult
  • Anti-HIV Agents / therapeutic use*
  • Antiretroviral Therapy, Highly Active
  • Biomarkers / blood
  • CD4-Positive T-Lymphocytes / enzymology
  • CD8-Positive T-Lymphocytes / enzymology
  • CD8-Positive T-Lymphocytes / metabolism
  • Cyclooxygenase 2 / blood
  • Cyclooxygenase 2 Inhibitors / therapeutic use*
  • Female
  • HIV Infections / drug therapy*
  • HIV Infections / immunology
  • HIV Infections / virology
  • Humans
  • Lymphocyte Activation / drug effects
  • Lymphocyte Count
  • Male
  • Membrane Glycoproteins / blood
  • Middle Aged
  • Perforin
  • Pore Forming Cytotoxic Proteins
  • T-Lymphocyte Subsets / metabolism
  • Treatment Outcome
  • Viral Load

Substances

  • Anti-HIV Agents
  • Biomarkers
  • Cyclooxygenase 2 Inhibitors
  • Membrane Glycoproteins
  • Pore Forming Cytotoxic Proteins
  • Perforin
  • Cyclooxygenase 2
  • ADP-ribosyl Cyclase 1