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Immune modulatory effects of cyclooxygenase type 2 inhibitors in HIV patients on combination antiretroviral treatment.
AIDS. 2006 Apr 04; 20(6):813-20.AIDS

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.

Authors+Show Affiliations

Department of Infectious Diseases, Ullevål University Hospital, Oslo, Norway. dag.kvale@medisin.uio.noNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

16549964

Citation

Kvale, Dag, et al. "Immune Modulatory Effects of Cyclooxygenase Type 2 Inhibitors in HIV Patients On Combination Antiretroviral Treatment." AIDS (London, England), vol. 20, no. 6, 2006, pp. 813-20.
Kvale D, Ormaasen V, Kran AM, et al. Immune modulatory effects of cyclooxygenase type 2 inhibitors in HIV patients on combination antiretroviral treatment. AIDS. 2006;20(6):813-20.
Kvale, D., Ormaasen, V., Kran, A. M., Johansson, C. C., Aukrust, P., Aandahl, E. M., Frøland, S. S., & Taskén, K. (2006). Immune modulatory effects of cyclooxygenase type 2 inhibitors in HIV patients on combination antiretroviral treatment. AIDS (London, England), 20(6), 813-20.
Kvale D, et al. Immune Modulatory Effects of Cyclooxygenase Type 2 Inhibitors in HIV Patients On Combination Antiretroviral Treatment. AIDS. 2006 Apr 4;20(6):813-20. PubMed PMID: 16549964.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Immune modulatory effects of cyclooxygenase type 2 inhibitors in HIV patients on combination antiretroviral treatment. AU - Kvale,Dag, AU - Ormaasen,Vidar, AU - Kran,Anne-Marte Bakken, AU - Johansson,Carl Christian, AU - Aukrust,Pål, AU - Aandahl,Einar Martin, AU - Frøland,Stig S, AU - Taskén,Kjetil, PY - 2006/3/22/pubmed PY - 2006/6/30/medline PY - 2006/3/22/entrez SP - 813 EP - 20 JF - AIDS (London, England) JO - AIDS VL - 20 IS - 6 N2 - 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. SN - 0269-9370 UR - https://www.unboundmedicine.com/medline/citation/16549964/Immune_modulatory_effects_of_cyclooxygenase_type_2_inhibitors_in_HIV_patients_on_combination_antiretroviral_treatment_ L2 - https://doi.org/10.1097/01.aids.0000218544.54586.f1 DB - PRIME DP - Unbound Medicine ER -