HIV, Tuberculosis
Conditions
Keywords
pharmacokinetics of rifabutin, HIV/TB co-infection, resource limited setting, AUC, Cmax, Cmin, Ctrough
Brief summary
To describe the pharmacokinetics of rifabutin 150 mg once daily versus rifabutin 300 mg thrice weekly in combination with LPV/r 400/100mg based HAART in HIV/TB infected patients
Detailed description
The overall aim of the project is to evaluate rifabutin as a replacement for rifampicin, for the combined treatment of tuberculosis and HIV infection. Rifabutin represents an alternative to rifampicin for HIV infected patients as its half-life is longer and the enzymatic induction effect appears to be less important on the associated ART drugs. This phase II trial is to determine precisely the pharmacokinetics parameters of rifabutin in combination with LPV/r regimens in Thai HIV/TB infected patients, in order to define optimal doses that will be further tested in a larger phase III trial comparing safety, tolerability and efficacy of rifabutin and rifampicin regimens.
Interventions
DRUGLopinavir/r will be supplied by NHSO/GPO
200/50 mg tablet LPV/rtv
DRUGRifabutin
Sponsors
Bamrasnaradura Infectious Diseases Institute
Chulalongkorn University
The HIV Netherlands Australia Thailand Research Collaboration
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
1. Confirmed HIV positive after voluntary counseling and testing 2. Aged \>18-60years of age 3. PI-naïve (NNRTI intolerance/failure) or PI experience ( TB developed during on salvage regimen) without prior PI mutation 4. Any CD4 cell count 5. ALT \<5 times ULN 6. Serum creatinine \<1.4 mg/dl 7. Hemaglobin \>7 mg/L 8. TB is diagnosed and planned to receive stable doses of rifabutin containing anti-TB therapy for at least another 4 week period after initiation of ART 9. No other active OI (CDC class C event), except oral candidiasis or disseminated MAC 10. Body weight \>40kg 11. Able to provide written informed consent
Exclusion criteria
1. Current use of steroid (except short course steroid for IRIS) and other immunosuppressive agents. 2. Current use of any prohibited medications related to drug pharmacokinetics. 3. Patients with current alcohol or illicit substance use that in the opinion of the site Principal Investigator would conflict with any aspect of the conduct of the trial. 4. Unlikely to be able to remain in follow-up for the protocol defined period. 5. Patients with proven or suspected acute hepatitis. Patients with chronic viral hepatitis are eligible provided ALT, AST \< 5 x ULN. 6. Karnofsky performance score \<30% 7. TB meningitis and bone/joints ( due to longer period of anti TB drug) 8. Pregnancy 9. Patient choose to use efavirenz, not LPV/r. However, in ART naïve, EFV is allowed after intensive PK of LPV/r and rifabutin at week 2-4.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| pharmacokinetics of rifabutin Cmax | 48 weeks | Cmax The peak plasma concentration of rifabutin after administration |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| viral load | 48 weeks | — |
| CD4 | 48 weeks | mean CD4 rise from baseline |
| Monodrug resistant TB | 48 weeks | — |
| death | 48 weeks | — |
| AIDS event | 48 weeks | — |
| TB cure | 48 weeks | — |
| adverse events | 48 weeks | number of participants with adverse events |
| Multidrug-resistant TB (MDR TB) | 48 weeks | — |
| TB treatment failure | 48 weeks | — |
| Extensively drug resistant TB (XDR TB) | 48 weeks | — |
| weight gain | 48 weeks | change from baseline in weight gain at 48 weeks |
| defervescence | 48 weeks | change from baseline in defervescence at 48 weeks |
| Karnofsky score | 48 weeks | change from baseline in Karnofsky score at 48 weeks |
| TB relapse | 48 weeks | — |
Countries
Thailand
Outcome results
None listed