A Study to Determine the Best Dose of Antivirals in Patients With Both TB and HIV

NCT ID: NCT00523458

Last Updated: 2011-07-22

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE4
• Total Enrollment: 5 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-07-31
• Study Completion Date: 2008-03-31

Brief Summary

Because drugs used to treat TB can reduce the amount of the anti-HIV drugs that reach the sites where the virus is located, this study is designed to see whether it is necessary to use higher doses of antiviral (anti-HIV) drugs while patients are receiving therapy with rifampin, one of the drugs commonly used to treat TB. Participants will be assigned to one of 4 arms (see below) and will be followed during the time when they are receiving both treatments.

Detailed Description

This is an open label, randomized study with 4 arms: 1.) Standard dose and 2.) high dose nevirapine; and 3.) standard dose and 4.) high dose efavirenz. Subjects in all 4 arms will also receive 2 nucleoside analog drugs. Patients will have routine monitoring for the treatment of TB and HIV, as well as some additional blood samples to follow the virus in the blood and to determine the effect of the TB therapy on the amounts of anti-HIV drugs that are in the body.

Conditions

HIV Infections; Tuberculosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1

Standard dose nevirapine (200 mg 2x daily) in combination with 2 nucleoside analogs

Group Type: ACTIVE_COMPARATOR

efavirenz or nevirapine

Intervention Type: DRUG

Patients co-infected with HIV and TB will receive either "standard" doses of nevirapine (200 mg 2x daily) or efavirenz (600 mg daily) or "high" doses of nevirapine (400 mg and 200 mg daily) or efavirenz (800 mg daily) that are chosen to compensate for the change in pharmacokinetics shown to occur when co-infected patients are treated with the antituberculous drug, rifampin.

2

High dose nevirapine (400 mg in the morning, 200 mg in the evening) in combination with 2 nucleoside analogs

Group Type: EXPERIMENTAL

efavirenz or nevirapine

Intervention Type: DRUG

Patients co-infected with HIV and TB will receive either "standard" doses of nevirapine (200 mg 2x daily) or efavirenz (600 mg daily) or "high" doses of nevirapine (400 mg and 200 mg daily) or efavirenz (800 mg daily) that are chosen to compensate for the change in pharmacokinetics shown to occur when co-infected patients are treated with the antituberculous drug, rifampin.

3

Standard dose efavirenz (600 mg at bedtime) in combination with 2 nucleoside analogs

Group Type: ACTIVE_COMPARATOR

efavirenz or nevirapine

Intervention Type: DRUG

Patients co-infected with HIV and TB will receive either "standard" doses of nevirapine (200 mg 2x daily) or efavirenz (600 mg daily) or "high" doses of nevirapine (400 mg and 200 mg daily) or efavirenz (800 mg daily) that are chosen to compensate for the change in pharmacokinetics shown to occur when co-infected patients are treated with the antituberculous drug, rifampin.

4

High dose efavirenz (800 mg at bedtime) in combination with 2 nucleoside analogs

Group Type: EXPERIMENTAL

efavirenz or nevirapine

Intervention Type: DRUG

Patients co-infected with HIV and TB will receive either "standard" doses of nevirapine (200 mg 2x daily) or efavirenz (600 mg daily) or "high" doses of nevirapine (400 mg and 200 mg daily) or efavirenz (800 mg daily) that are chosen to compensate for the change in pharmacokinetics shown to occur when co-infected patients are treated with the antituberculous drug, rifampin.

Interventions

efavirenz or nevirapine

Patients co-infected with HIV and TB will receive either "standard" doses of nevirapine (200 mg 2x daily) or efavirenz (600 mg daily) or "high" doses of nevirapine (400 mg and 200 mg daily) or efavirenz (800 mg daily) that are chosen to compensate for the change in pharmacokinetics shown to occur when co-infected patients are treated with the antituberculous drug, rifampin.

Intervention Type: DRUG

Other Intervention Names

Sustiva (efavirenz); Viramune (nevirapine)

Eligibility Criteria

Inclusion Criteria

• ARV naïve subjects
• Documented HIV infection
• Documented TB infection
• Platelet count 40,000/mm3
• Hemoglobin ≥8.0 g/dL
• Absolute neutrophil count (ANC) >500/mm3
• AST (SGOT), ALT (SGPT), and alkaline phosphatase <3 X ULN
• Total bilirubin <2.5 x ULN
• Calculated creatinine clearance ≥60 mL/min
• For women of reproductive potential, negative urine pregnancy test

• Women who are breast-feeding
• Known allergy/sensitivity to study drug(s) or their formulations
• Patients with other OIs or intercurrent illness that could affect their ability to take study drugs

Exclusion Criteria

• Unable to provide informed consent.
• History drug abuse that the investigators suspect will interfere with compliance to study medications and visits.
• Patients on hemodialysis.
• Tuberculosis meningitis.
• Women with CD4 > 250 and men with CD4 > 400 due to higher risk of hepatotoxicity related to use of NVP.
• Positive serology for hepatitis C.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Stanford University

OTHER

Sponsor Role: lead

Responsible Party

Stanford University School of Medicine

Principal Investigators

Terrence F Blaschke, M.D.

Role: PRINCIPAL_INVESTIGATOR

Stanford University

Locations

Hospital Universitario Prof. Edgard Santos/Universidade Federal da Bahia

Salvador, Estado de Bahia, Brazil

Countries

Brazil

Other Identifiers

Stanford Protocol ID: 95564

Identifier Type: -

Identifier Source: org_study_id