A 14day treatment with a cyclooxygenase 2 COX2 inhibitor reduces inflammation in the lymphoid tissue

1
A 14-day treatment with a cyclooxygenase 2
(COX-2) inhibitor reduces inflammation in the
lymphoid tissues of HIV-infected patients without
HAART - A pilot study with positron emission
tomography (PET/CT) assessment
2
Background

• Immune activation plays a major role in the
  pathogenesis of several complications induced by
  HIV infection (including immunodeficiency)
• Previous studies by biopsy or PET/CT have
  demonstrated persistent inflammation in the
  lymphoid organs of HIV infected patients, with
  potentially irreversible consequences on the
  properties of these microenvironments (Schacker
  et al. 2002 Nies-Kraske et al. 2009)

3
Background

• Macrophages infected with HIV (or exposed to
  extracellular Tat) upregulate COX-2 and the
  release of PGE2 participates in the neurological
  complications of HIV infection (Blanco et al.
  2008)

4
Hypothesis

• COX-2 is upregulated in the lymphoid organs of
  HIV infected individuals
• PGE2 secretion in the lymphoid tissues
  contributes to local inflammation with
• Short-term consequences CD4 T cells entrapment
• Long-term consequences collagen deposit and
  microenvironment defects

5
Objective

• To determine if blocking PGE2 secretion by a
  COX-2 inhibitor can reduce FDG uptake in the
  lymphoid tissues and improve immunologic
  parameters of HIV infected patients without
  HAART.

6
Methodology (1)

• 7 patients infected with HIV-1 (6 with chronic
  infection and 1 with primary HIV infection)
  without HAART
• FDG PET/CT studies were performed following
  standard oncological procedures on day 0 and 14
  (posttreatment with Celecoxib 200 mg bid).
• Any increased nodal uptake in the cervical,
  axillary, mediastinal, mesenteric, iliac and
  inguinal regions (regions of interests ROIs)
  was recorded.

7
Methodology (2)

• The Standardized Uptake Value (SUVmax) was
  measured in the ROIs and the lesion to liver
  activity ratios were calculated (SUV ratios).
• The sum of SUV ratios were calculated for each
  patient to obtain a global metabolic score

8
Results

• At baseline, all patients showed increased FDG
  uptake in various nodal stations.

9

10
Treatment with celecoxib reduced metabolic score
in 6/7 patients
p0.0309
Posttreatment
Pretreatment
11
Treatment with celecoxib reduced metabolic score
in 6/7 patients
12
Treatment with celecoxib improved peripheral
CD4/CD8 ratios
p0.0296
13
Conclusions

• A short-term treatment with celecoxib
• Improved metabolic score in 6 out 7 patients
• Improved CD4/CD8 ratios in all patients
• Marginally reduced the frequency of CD38 CD8 T
  cells (but this failed to be statistically
  significant)
• Had no impact on viral load
• Secretion of PGE2 within the lymphoid tissues
  could contribute to local inflammation and
  preferential entrapment of CD4 cells.