HIV Infections, Tuberculosis
Conditions
Keywords
Co-infection, Tuberculosis, HIV, Drug interactions, Non nucleoside reverse transcriptase inhibitors, Therapy, Treatment Naive
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.
Interventions
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.
Sponsors
Stanford University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
Brazil
Outcome results
None listed