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

Stanford University

Status and phase: Terminated; Phase 4

Conditions: Tuberculosis; HIV Infections

Treatments: Drug: efavirenz or nevirapine

Study type: Interventional

Funder types: Other

Identifiers

NCT00523458

Stanford Protocol ID: 95564

Details and patient eligibility

About

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.

Full 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.

Enrollment: 5 patients

Sex: All

Ages: 18+ years old

Volunteers: No 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

5 participants in 4 patient groups

1

Active Comparator group

Description:

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

Treatment:

Drug: efavirenz or nevirapine

2

Experimental group

Description:

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

Treatment:

Drug: efavirenz or nevirapine

3

Active Comparator group

Description:

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

Treatment:

Drug: efavirenz or nevirapine

4

Experimental group

Description:

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

Treatment:

Drug: efavirenz or nevirapine