An evaluation of the impact of early initiation of Highly Active Anti-Retroviral Therapy (HAART) on Tuberculosis (TB) treatment outcomes for TB patients co-infected with Human Immunodeficiency Virus (HIV)

• Register: ISRCTN
• Last refreshed on: 13 January 2015
• Main ID: ISRCTN77861053
• Date of registration: 29/03/2006
• Prospective Registration: Yes
• Primary sponsor: World Health Organization (WHO) (Switzerland)
• Public title: An evaluation of the impact of early initiation of Highly Active Anti-Retroviral Therapy (HAART) on Tuberculosis (TB) treatment outcomes for TB patients co-infected with Human Immunodeficiency Virus (HIV)
• Date of first enrolment: 30/05/2006
• Target sample size: 1900
• Recruitment status: Completed
• URL: http://isrctn.com/ISRCTN77861053
• Study type: Interventional
• Study design: Randomised controlled trial (Treatment)

Countries of recruitment

South Africa, Tanzania, Uganda, Zambia

Contacts

• Name: Philip Onyebujoh

Key inclusion & exclusion criteria

Inclusion criteria: 1. Aged 18 to 65 years
2. HIV treatment naive patients (established by history)
3. CD 4 T-cell count between 220-500 cells/l
4. No history of previous anti-TB chemotherapy
5. A traceable home address and contact details to facilitate home visits with a firm commitment to remain traceable and to be able to access a defined treatment/service point for 24 months
6. Not enrolled in any other drug or treatment trials
7. Informed consent for HIV testing (since the study population will be smear positive TB patients co-infected with HIV)
8. Informed consent to participate in the trial
9. For female subjects, the following conditions are to be met:
9.1. Has been post-menopausal for at least one year, or
9.2. Is surgically incapable of bearing children, or
9.3. Is of childbearing potential and all of the following conditions are met:
9.3.1. Had a normal menstrual flow within one month before study entry
9.3.2. Has a negative pregnancy test (urine) immediately before study entry (and later confirmed by serum pregnancy test)
9.3.3. Must agree to use an accepted method of contraception (i.e. barrier methods or intrauterine device [IUD]). The subject must agree to continue with the same method throughout the study
Note: If a patient is using a long-acting hormonal contraceptive (such as Depot-Provera), the patient can be enrolled in the study, however she should be advised to use it in conjunction with a barrier method or IUD due to the known pharmacokinetic interaction between the various study medications and hormonal contraceptives. If an oral hormonal agent is in use, the patient should be advised to change the method of contraception in favour of barrier methods.
Exclusion criteria: 1. Evidence (laboratory and clinical history) of pre-existing non-tuberculosis disease likely to affect the response to, or assessment of treatment effects or represent contraindications to the study medication:
1.1. Diabetes mellitus
1.2. Liver impairment (alanine aminotransferase [ALT] or aspartate aminotransferase [AST] greater than 2 x the upper limit of normal value)
1.3. Renal failure (serum creatinine greater than 2.0 mg/dl)
1.4. Epilepsy
1.5. Optical neuritis
1.6. Pancreatitis (lipase greater than 140 U/l)
1.7. Neutropenia (total neutrophil count less than 1200 cells/l)
1.8. Severe anaemia (haemoglobin less than 6.9 g/dl)
1.9. Any other condition that in the view of the country Principal Investigator represents a contraindication to the study medication
2. Mental illness (clinical suspicion of schizophrenia, manic-depressive illness, dementia)
3. Stage IV disease (according to World Health Organization [WHO] staging system)
4. Weight below 30 kg
5. Moribund or clinical evidence of severe illness

Age minimum:
Age maximum:
Gender: Both

Health Condition(s) or Problem(s) studied

Tuberculosis (TB) and Human Immunodeficiency Virus (HIV) co-infections
Infections and Infestations
Human immunodeficiency virus (HIV)

Intervention(s)

Placebo controlled trial.

Patients with TB-HIV co-infection with CD4 counts above 220, to be randomised into combined treatment with anti-TB and HIV medications and then HAART after six months, or anti-TB plus placebo for six months and then HAART thereafter.

All patients will be on HAART after six months, and post-trial medication is provided by the governments of participating countries.

Primary Outcome(s)

The proportion of subjects reaching the composite endpoint of treatment failure or death at six months after the initiation of short-course chemotherapy for TB.

Secondary Outcome(s)

1. The proportion of patients with TB relapse in the 24 months after initiation of short course chemotherapy in the two treatment groups
2. The proportion of patients reaching the multiple endpoint of treatment failure, relapse or death evaluated at 24 months after TB treatment initiation
3. The safety and tolerability of HAART used concomitantly with anti-TB medication

Secondary ID(s)

South Africa (A50560), Zambia (A50636), Uganda (A30224) and Tanzania (A30213)

Source(s) of Monetary Support

World Health Organization (WHO) (Switzerland), US Agency for International Development (USAID) (USA), GlaxoSmithKline (GSK) - drug supply, Merck & Co Inc. - drug supply