AIDS With Tuberculosis
Conditions
Keywords
HIV, Tuberculosis, Antituberculosis drugs
Brief summary
Tuberculosis (TB) is a leading cause of death in HIV-infected individuals. There are insufficient data correlating concentrations of anti-TB drugs with treatment response. We hypothesize that sub-therapeutic concentrations of anti-TB drugs are associated with inadequate TB treatment response to Mycobacterium tuberculosis.
Detailed description
During the study periodic monitoring will be conducted to ensure that the protocol and Good Clinical Practices (GCPs) are being followed.The monitors may review source documents to confirm that the data recorded on CRFs is accurate. The study site may be subject to review by the Institutional Review Board (IRB) and/or appropriate regulatory authorities. A CRF will be completed for each included subject and will be signed by the investigator or by an authorized staff member to attest that the data is true. Any corrections to entries made in the CRFs, source documents must be dated, initialed and explained (if necessary) and should not obscure the original entry. Qualit assurance will as also be performed regularly on the CRFs. The primary end point will be analyzed using Time to event (cure, death, relapse etc)analysis and failure rates and hazard ratios will be calculated accordig to categorical drug concentrations with proposed cutt offs. Secondary end points will be analysed using time to event for occurence of toxicities which will also be corelated to the drug concentrations.
Interventions
DRUGRifampicin, Isoniazid, Ethambutol, Pyrazinamide
Rifampicin, Isoniazid, Ethambutol, Pyrazinamide: 3, 4 or 5 tablets daily for weight below 55kg, above 55kg or above 70kg respectively for first 2 months followed by Rifampicin, Isoniazid: 3, 4 or 5 tablets daily for patients' weight below 55kg, above 55kg or above 70kg respectively for 4 months
Sponsors
Makerere University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Evidence of a personally signed and dated informed consent * Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures. * Age of ≥18 years * First episode of pulmonary TB i.e. proven or highly suspected TB considered for TB treatment qualifying for 6 months anti-Tb drugs regimen * Confirmed HIV-1 infection
Exclusion criteria
* Unable to provide informed consent * Documented or highly suspected TB infection of any organs/systems other than the lung requiring TB treatment longer than 6 months * Previously treated for a mycobacterial infection (TB or atypical mycobacterial infection, active or latent) * Pregnancy or planned pregnancy within the next year * Unwillingness to perform pregnancy test * Decompensated liver disease and/or aminotransferases \>5x ULN * GFR \< 50 ml/min * Co-morbidities reducing life expectancy to \<1 year (e.g. cancer) * Patient wishes to take part in another interventional study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| clinical outcome | At the end of treatment (6 months after enrolmet) | To investigate the association between serum concentrations of antituberculosis drugs and tuberculosis treatment response in HIV-TB-co-infected individuals. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cmax | At 2 weeks, 8 weeks and 24 weeks after anti-tuberculosis drug initiation | To investigate the steady-state pharmacokinetic parameters of anti-TB drugs at different time-points over the course of TB-treatment |
| Number of adverse events | 2 weeks, 8 weeks and 24 weeks after anti-tuberculosis drug initiation | To assess the safety and tolerability of anti-TB drugs based on the WHO guidelines |
| ART trough levels | At 2 weeks, 8 weeks and 24 weeks after anti-tuberculosis drug initiation | To correlate the effect of anti-TB drugs on plasma concentrations of efavirenz or protease inhibitors and vice versa. |
| Isoniazid Cmax | At 2 weeks, 8 weeks and 24 weeks | To evaluate the effect of acetylator geno-and phenotype (NAT-2 gene) on isoniazid plasma concentrations and toxicity |
Countries
Uganda
Contacts
Primary ContactAndrew Kambugu, MMED
Outcome results
None listed