Condition category
Infections and Infestations
Date applied
Date assigned
Last edited
Retrospectively registered
Overall trial status
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information



Primary contact

Prof Gary Maartens


Contact details

Division of Pharmacology
University of Cape Town Medical School
Old Main Building
Groote Schuur Hospital
Cape Town
South Africa

Additional identifiers

EudraCT number number

Protocol/serial number


Study information

Scientific title



Study hypothesis

We propose a randomised placebo-controlled trial of prednisone as an adjunct in the management of HIV-infected patients with mild to moderate Tuberculosis-associated Immune Reconstitution Inflammatory Syndrome (TB-IRIS). This syndrome manifests as a paradoxical worsening of clinical features of tuberculosis after commencing Highly Active Antiretroviral Therapy (HAART). We hypothesise a reduction in the requirement for hospitalisation and therapeutic procedures among patients receiving prednisone.

Ethics approval

Not provided at time of registration

Study design

Randomised placebo-controlled trial

Primary study design


Secondary study design

Randomised controlled trial

Trial setting

Not specified

Trial type


Patient information sheet


HIV and Tuberculosis-associated Immune Reconstitution Inflammatory Syndrome


Randomization to oral prednisone 1.5 mg/kg for 2 weeks followed by 0.75 mg/kg for 2 weeks or identical placebo medication.

Intervention type



Not Specified

Drug names


Primary outcome measure

Combined hospitalisation and procedures endpoint (cumulative duration of hospitalisation in days + outpatient therapeutic procedures counted as one day)

Secondary outcome measures

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

Overall trial start date


Overall trial end date


Reason abandoned (if study stopped)


Participant 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.

Participant type


Age group




Target number of participants


Participant 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

Recruitment start date


Recruitment end date



Countries of recruitment

South Africa

Trial participating centre

Division of Pharmacology
Cape Town
South Africa

Sponsor information


University of Cape Town - Research Ethics Committee, Faculty of Health Sciences (South Africa)

Sponsor details

Research Ethics Committee
Faculty of Health Sciences
Old Main Building
Groote Schuur Hospital
Cape Town
South Africa

Sponsor type




Funder type

Research council

Funder name

Medical Research Council, South Africa (no reference number provided)

Alternative name(s)

Funding Body Type

Funding Body Subtype


Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Basic results (scientific)

Publication list

1. 2012 results in

Publication citations

  1. Results

    Meintjes G, Skolimowska KH, Wilkinson KA, Matthews K, Tadokera R, Conesa-Botella A, Seldon R, Rangaka MX, Rebe K, Pepper DJ, Morroni C, Colebunders R, Maartens G, Wilkinson RJ, Corticosteroid-modulated immune activation in the tuberculosis immune reconstitution inflammatory syndrome., Am. J. Respir. Crit. Care Med., 2012, 186, 4, 369-377, doi: 10.1164/rccm.201201-0094OC.

Additional files

Editorial Notes