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

Purpose

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	Intervention	Phase
HIV Infections Tuberculosis	Drug: efavirenz or nevirapine	Phase 4


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment

Resource links provided by NLM:

MedlinePlus related topics: HIV/AIDS Tuberculosis

Drug Information available for: Nevirapine Efavirenz

Genetic and Rare Diseases Information Center resources: Tuberculosis

U.S. FDA Resources

Further study details as provided by Stanford University:

Primary Outcome Measures:

Decline in HIV RNA in plasma Rise in CD4 cell count [ Time Frame: Baseline, and Weeks 8, 20 and 32 ] [ Designated as safety issue: No ]
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


Enrollment:	5
Study Start Date:	July 2007
Study Completion Date:	March 2008
Primary Completion Date:	March 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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)

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.

Eligibility


Ages Eligible for Study:	18 Years and older (Adult, Senior)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

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

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00523458

Locations


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

Sponsors and Collaborators

Stanford University

Investigators


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

More Information


Responsible Party:	Terrence F Blaschke, Principle Investigator, Stanford University School of Medicine
ClinicalTrials.gov Identifier:	NCT00523458 History of Changes
Other Study ID Numbers:	Stanford Protocol ID: 95564
Study First Received:	August 29, 2007
Last Updated:	July 20, 2011
Health Authority:	United States: Institutional Review Board United States: Federal Government Brazil: National Committee of Ethics in Research

Keywords provided by Stanford University:


Co-infection Tuberculosis HIV Drug interactions	Non nucleoside reverse transcriptase inhibitors Therapy Treatment Naive

Additional relevant MeSH terms:


HIV Infections Tuberculosis Lentivirus Infections Retroviridae Infections RNA Virus Infections Virus Diseases Sexually Transmitted Diseases, Viral Sexually Transmitted Diseases Immunologic Deficiency Syndromes Immune System Diseases Mycobacterium Infections Actinomycetales Infections Gram-Positive Bacterial Infections Bacterial Infections Efavirenz	Nevirapine Reverse Transcriptase Inhibitors Nucleic Acid Synthesis Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Anti-Retroviral Agents Antiviral Agents Anti-Infective Agents Cytochrome P-450 CYP2C9 Inhibitors Cytochrome P-450 Enzyme Inhibitors Cytochrome P-450 CYP2C19 Inhibitors Cytochrome P-450 CYP2B6 Inducers Cytochrome P-450 Enzyme Inducers Cytochrome P-450 CYP3A Inducers Anti-HIV Agents

HIV Infections
Tuberculosis
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Efavirenz

Nevirapine
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Cytochrome P-450 CYP2C9 Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Cytochrome P-450 CYP2C19 Inhibitors
Cytochrome P-450 CYP2B6 Inducers
Cytochrome P-450 Enzyme Inducers
Cytochrome P-450 CYP3A Inducers
Anti-HIV Agents

ClinicalTrials.gov processed this record on September 28, 2016

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