Clinical trial NCT00523458: A Study to Determine the Best Dose of Antivirals in Patients With Both TB and HIV
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: HIV Infections
Tuberculosis
Keywords: Co-infection
Tuberculosis
HIV
Drug interactions
Non nucleoside reverse transcriptase inhibitors
Therapy
Treatment Naive
Lead sponsor: Stanford University
Sponsor class: OTHER
First posted: 2007-08-31
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Decline in HIV RNA in plasma Rise in CD4 cell count
timeFrame: Baseline, and Weeks 8, 20 and 32
Secondary outcomes:
Other outcomes:
Locations:
city: Salvador
country: Brazil
facility: Hospital Universitario Prof. Edgard Santos/Universidade Federal da Bahia
state: Bahia
Study officials:
affiliation: Stanford University
name: Terrence F Blaschke, M.D.
role: PRINCIPAL_INVESTIGATOR
References: