HIV and Tuberculosis-associated Immune Reconstitution Inflammatory Syndrome Infections and Infestations Human immunodeficiency virus (HIV)
Conditions
Interventions
Randomization to oral prednisone 1.5 mg/kg for 2 weeks followed by 0.75 mg/kg for 2 weeks or identical placebo medication.
Sponsors
University of Cape Town - Research Ethics Committee, Faculty of Health Sciences (South Africa)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: A. Age 18 years and over B. Informed consent (written) C. Prior to the introduction of HAART the following criteria must be met for the diagnosis of TB-IRIS to be considered: 1. The patient has HIV infection 2. The patient should be antiretroviral-naïve (excluding receipt of antiretroviral treatment within mother to child transmission programmes ? Nevirapine single-dose with or without Zidovudine in the third trimester) 3. The patient has microbiologic, histologic or very strong clinical evidence of tuberculosis 4. There has been a documented improvement in symptoms, Karnofsky score and/or weight, resolution of fever and clinical and radiological stabilization during the intensive phase of multidrug TB therapy 5. That adherence with anti-TB treatment is >80% 6. That the infecting strain of M. tuberculosis is sensitive to rifampicin, if this result is available D. Consider TB-IRIS if, within 3 months of the introduction of multi-drug HAART 1. Adherence with HAART is documented and the patient was on anti-tuberculous therapy when HAART commenced 2. There are new or recurrent constitutional symptoms PLUS one or more of: i. New or expanding lymph nodes (>20 mm or >50% in volume) ii. New or expanding tuberculous cold abscesses (e.g. paraspinal) iii. New or expanding pulmonary infiltrates (radiographically confirmed) iv. New or enlarging serous effusions (pericardial, pleural or ascitic) Patients presenting with other manifestations of TB-IRIS (e.g. central nervous system [CNS] tuberculoma) will not be included in this study.
Exclusion criteria
Exclusion criteria: 1. Previous systemic steroid therapy as part of the management of tuberculosis 2. Pregnancy 3. Uncontrolled Diabetes Mellitus 4. Adrenal failure 5. Severe TB-IRIS (these cases will receive open label corticosteroids) manifested by: a. Respiratory failure (pO2 <8 kPa) b. Altered level of consciousness or new focal neurological signs c. Compression of vital structures (e.g. bronchostenosis) 6. Kaposi?s sarcoma
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Combined hospitalisation and procedures endpoint (cumulative duration of hospitalisation in days + outpatient therapeutic procedures counted as one day) | — |
Secondary
| Measure | Time frame |
|---|---|
| Radiological Endpoints: A significant improvement in radiological manifestations of IRIS: 1. For Chest X Ray pulmonary infiltrates, a significant reduction in composite infiltrate score (6 zones each measured for degree of infiltrate by Radiologist to give composite score) 2. For large nodes noted on the Chest X Ray, a significant reduction in size 3. For computed tomography (CT) scans, a significant reduction in infiltrate or node size 4. For peripheral & abdominal nodes, a significant reduction in volume as measured by ultrasound 5. For cold abscesses, a significant reduction in volume as measured by ultrasound Other Secondary Endpoints: 1. 50% reduction in symptom score (Wilson 2004) 2. A significant improvement in the Quality of Life MOS-HIV score 3. Improvement in Karnofsky score of greater than 10 4. Corticosteroid side effects a. New onset of diabetes b. New onset of hypertension c. Psychological side effects d. Onset of new opportunistic infection/cancer such as Kaposi?s sarcoma, Herpes simplex lesions, Herpes zoster lesions 5. 50% reduction in C-Reactive Protein (CRP) value 6. Weight gain 7. Mortality 8. The need to stop HAART, TB therapy or study drug 9. Adherence with HAART and study drug as assessed by pill count and adherence with TB treatment as assessed by TB clinic card assessment 10. Recurrence of IRIS manifestations within the 12 week study period 11. In patients with an Alkaline Phosphatase or gamma glutamyl transpeptidase (GGT) that was elevated more than 2 x upper limit of normal (ULN) at baseline, a reduction of 50% from the baseline value 12. CD4 and Viral load 13. For ascites, reduction in abdominal girth | — |
Countries
South Africa
Outcome results
None listed