Pharmacokinetics of Rifabutin Combined With Antiretroviral Therapy in Patients With TB/HIV Co-infection in Vietnam

French National Agency for Research on AIDS and Viral Hepatitis

Status and phase

Completed

Phase 2

Conditions

Tuberculosis

HIV Infections

Treatments

Drug: rifabutin in combination with lopinavir boosted by ritonavir - dosing schedule 2

Drug: rifabutin in combination with lopinavir boosted by ritonavir - dosing schedule 1

Study type

Interventional

Funder types

Other

Identifiers

NCT00651066

ANRS12150b

Details and patient eligibility

About

The overall aim of the project is to evaluate rifabutin (RBT) as a replacement for rifampicin (RMP), for the combined treatment of tuberculosis and HIV infection. RBT represents an alternative to RMP for HIV infected patients as its half-life is longer and the enzymatic induction effect appears to be less important on the associated antiretroviral therapy (ART) drugs.

This phase II trial is to determine precisely the pharmacokinetics parameters of RBT in combination with different ART regimens in Vietnamese HIV infected patients with pulmonary tuberculosis, in order to define optimal doses that will be further tested in a larger phase III trial comparing safety, tolerability and efficacy of RBT and RMP regimens.

Full description

Patients will be offered to participated in the study when they start TB treatment. All the enrolled patients will immediately be switched to rifabutin and randomized, to one of the RBT doses that will be then adapted to the allocated RBT regimen according to a cross over scheme. Three full pharmacokinetics profile will be performed at different time point : before initiation of ARV, after three weeks of the first RBT dosage and after three weeks of the secondRBT dosage. Patients will then be referred to the national program for further treatment. A follow-up visit will be planned at the end of the antiTB treatment.

Enrollment

47 patients

Sex

All

Ages

18 to 65 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Pulmonary tuberculosis defined as either
- at least 2 sputum smears positive for AFB
- 1 sputum smear positive for AFB and a chest radiograph compatible with active tuberculosis
- 1 sputum culture positive and and a chest radiograph compatible with active tuberculosis
- a clinical history and chest radiograph compatible with active tuberculosis and 2 sputum smear negative for AFB
Positive HIV antibody and CD4 count <=250 /mm3
Weight > 40 kg
No history of ART
No grade 3 or 4 clinical or laboratory findings
Negative pregnancy test and appropriate contraceptive measures during the duration of the trial for female of childbearing age
Having a firm home address that is readily accessible
Karnofsky score>=80%

Exclusion criteria

History of TB or MDR TB treatment
Concomitant OI requiring additional anti-infectious treatment
Formal contraindication to any drug used in the trial
Diabetes mellitus requiring drug treatment
Recreational drug or alcohol abuse
History of drug hypersensitivity to TB or related medications
Interrupted TB therapy for more than 1 week
Less than 90% adherent to first 6 weeks of intensive phase chemotherapy
Mental illness that could impair ability to give informed consent or result in poor adherence to trial protocol and therapy
Neutropenia <1200 /L, anaemia <6.8 g/dL, liver function test > grade 2
Requiring concomitant medications that may potentially interact with study drugs
Pregnant or lactating women
Karnofsky score >80%
Any condition rendering the patient unable to understand the nature, scope, and possible consequences of thes study and to provide consent