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

Sponsor

Stanford University (Other)

Overall Status

Terminated

CT.gov ID

NCT00523458

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

0.6

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
HIV Infections Tuberculosis	Drug: efavirenz or nevirapine	Phase 4

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

5 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Study Start Date :

Jul 1, 2007

Actual Primary Completion Date :

Mar 1, 2008

Actual Study Completion Date :

Mar 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 1 Standard dose nevirapine (200 mg 2x daily) in combination with 2 nucleoside analogs	Drug: 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. Other Names: Sustiva (efavirenz) Viramune (nevirapine)
Experimental: 2 High dose nevirapine (400 mg in the morning, 200 mg in the evening) in combination with 2 nucleoside analogs	Drug: 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. Other Names: Sustiva (efavirenz) Viramune (nevirapine)
Active Comparator: 3 Standard dose efavirenz (600 mg at bedtime) in combination with 2 nucleoside analogs	Drug: 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. Other Names: Sustiva (efavirenz) Viramune (nevirapine)
Experimental: 4 High dose efavirenz (800 mg at bedtime) in combination with 2 nucleoside analogs	Drug: 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. Other Names: Sustiva (efavirenz) Viramune (nevirapine)

Outcome Measures

Primary Outcome Measures

Decline in HIV RNA in plasma Rise in CD4 cell count [Baseline, and Weeks 8, 20 and 32]
These laboratory measures would be used to determine if there was a difference in the ARV failure rate between patients receiving standard dose vs high dose treatment with NNRTIs

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

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.
Evidence for active hepatitis B including positive serologies for HBsAg, HBeAg, or HBV-DNA. Note: If anti-HBs is positive, patient is eligible for study if liver enzymes are within the parameters indicated in the inclusion criteria
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