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

• Status: Completed
• Trial end date: 2010-10-01
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: French National Agency for Research on AIDS and Viral Hepatitis
• Treatments: Efavirenz; Lopinavir; Nevirapine; Rifabutin; Ritonavir

Criteria

Inclusion Criteria:

• Pulmonary tuberculosis (proven by AFB positive sputum or culture)

• Having completed and adhered to 6 wks of intensive phase TB chemotherapy

• Positive HIV antibody and CD4 count >50 /mm3 and <=200

• Weight > 50 kg

• No ART in the preceding 3 months

• No more than 2 weeks or ART previously

• 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 within the 3 years preceding the presenting episode of TB

• Previous treatment for MDR TB

• 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