Tuberculosis (TB) and Human immunodeficiency virus (HIV) Infections and Infestations Human immunodeficiency virus (HIV)
Conditions
Interventions
Patients are assigned to the following groups:
1. TB/HIV co-infected (220 - 349 CD4 T cells/µl) treated with anti-TB chemotherapy and Highly Active Anti-Retroviral Therapy (HAART)
2. TB/HIV co-infecte
Sponsors
World Health Organization (WHO) (Switzerland)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Aged 18 to 65 years 2. Human Immunodeficiency Virus (HIV) treatment-naive patients (established by history) 3. No history of previous anti-TB chemotherapy within the previous 24 months 4. 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 5. Not currently enrolled in any other drug or treatment trials 6. Informed consent for HIV testing and PK testing 7. Informed consent to participate in the trial 8. For female subjects, the following conditions are to be met: 8.1. Has been post-menopausal for at least one year, or 8.2. Is surgically incapable of bearing children, or 8.3. Is of childbearing potential and all of the following conditions are met: 8.3.1. Has a negative pregnancy test (urine) immediately before study entry (and later confirmed by a another pregnancy test) 8.3.2. 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 will be advised to change the method of contraception in favour of barrier methods. No patient will be enrolled who does not accept to use barrier methods or IUD for contraception.
Exclusion criteria
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 2.5 x the upper limit of normal value) 1.3. Renal failure (serum creatinine greater than 1.5 x the upper limit of normal value) 1.4. Epilepsy 1.5. Optical neuritis 1.6. Pancreatitis (lipase greater than 1.5 x the upper limit of normal value) 1.7. Neutropenia (total neutrophil count less than 1200 cells/l) 1.8. Anaemia (haemoglobin less than 8 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 requiring concomitant medications that may potentially interact with study drugs (according to WHO staging system) 4. Weight below 30 kg 5. Moribund or clinical evidence of severe illness 6. Patients exposed to other medication that may (on the basis a known interaction, or a strong theoretical basis) affect study drug levels. Exclusion of a volunteer on the basis of a potential interaction will be at the discretion of the principal investigator 7. Of childbearing age and refusing to use either barrier or IUD method of contraceptive for the duration of the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To investigate the bioavailability of anti-tuberculosis drugs and anti-retroviral drugs administered in fixed dose combinations to HIV/TB co-infected immuno-compromised individuals commencing concomitant HIV and TB therapy compared with anti-retroviral drugs administered to HIV-infected patients without clinical TB and anti-tuberculosis drugs to TB patients with HIV commencing TB therapy only thereby determining the effects of the level of immunosuppression on the bioavailability of the drugs and any drug interactions. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Bioavailability of both Antiretroviral drugs and anti-TB drugs (rifampicin and isoniazid) as affected by CD4 count levels in co-infected TB-HIV patients (Comparison of drug levels of HAART by CD4 count stratum, stratified by presence/absence of ARVs) 2. Bioavailability of anti TB- drugs as affected by drug-drug interactions with anti-retroviral drugs in co-infected TB-HIV patients (comparison of TB drug levels between subjects given both ARVs and anti-TB drugs and those given anti-TB drugs alone, stratified by CD4 count stratum) 3. Homogeneity between drug-drug interactions over the two CD4 strata, or extent of modification by CD4 count of the effect of drug-drug interaction 4. Bioavailability of anti-retroviral drugs as affected by drug-drug interactions with anti-TB medications (comparison of ARV drug levels between HIV infected non TB infected individuals with CD4 count less than 200 cells/ µl given only ARVs and TB/HIV co-infected subjects at the same CD4 count given both anti-TB and HAART) 5. Safety parameters - including biochemical and haematological Adverse Events (AE) and Serious Adverse Events (SAE) | — |
Countries
South Africa
Outcome results
None listed