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

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.

Study Overview

• Status: Terminated
• Conditions: HIV Infections; Tuberculosis
• Intervention / Treatment: Drug: efavirenz or nevirapine

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 Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 4

Contacts and Locations

Study Locations

• Brazil
  • Bahia
    • Salvador, Bahia, Brazil, 40110-160
      • Hospital Universitario Prof. Edgard Santos/Universidade Federal da Bahia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / 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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Decline in HIV RNA in plasma Rise in CD4 cell count	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	Baseline, and Weeks 8, 20 and 32

Collaborators and Investigators

• Sponsor: Stanford University
• Investigators: Principal Investigator: Terrence F Blaschke, M.D., Stanford University

Study record dates

Study Major Dates

• Study Start: July 1, 2007
• Primary Completion (Actual): March 1, 2008
• Study Completion (Actual): March 1, 2008

Study Registration Dates

• First Submitted: August 29, 2007
• First Submitted That Met QC Criteria: August 29, 2007
• First Posted (Estimate): August 31, 2007

Study Record Updates

• Last Update Posted (Estimate): July 22, 2011
• Last Update Submitted That Met QC Criteria: July 20, 2011
• Last Verified: July 1, 2011

More Information

Terms related to this study

• Keywords: HIV; Tuberculosis; Therapy; Treatment Naive; Drug interactions; Co-infection; Non nucleoside reverse transcriptase inhibitors
• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Mycobacterium Infections; Tuberculosis; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 CYP2C9 Inhibitors; Cytochrome P-450 CYP2C19 Inhibitors; Nevirapine; Efavirenz
• Other Study ID Numbers: Stanford Protocol ID: 95564