A Pharmacokinetic Study to Assess Nevirapine [Viramune] Levels in HIV Infected Patients With Impaired Hepatic Functions

Study Overview
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Brief Summary
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The objective of this study was to evaluate the steady-state clearance of nevirapine among HIV-1 positive patients with hepatic fibrosis, and to examine whether the degree of hepatic impairment influences clearance.

Official Title
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A Pharmacokinetic Study to Assess Nevirapine Levels in HIV-infected Patients With Impaired Hepatic Function

Conditions
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HIV Infections, Hepatic Insufficiency

Intervention / Treatment
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* Drug: nevirapine


Participation Criteria
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Eligibility Criteria
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INCLUSION Male or female subjects >=18 years of age with HIV-1 infection and chronic liver disease as reflected by a documented biopsy with hepatic fibrosis present. a. Participants must be receiving nevirapine 200 mg twice daily as part of a stable ARV regimen for a minimum of 6 weeks prior to trough level sample collection. b. Participants receiving nevirapine 400 mg once daily as part of a stable ARV regimen for a minimum of 6 weeks, who are willing to switch to nevirapi0 mg twice daily for a minimum of 14 days prior to trough collection. Participants must have uoxylin and Eosin (H and E) stained slide and one trichrome stained pathology slide available at the time of enrollment. There is no time restriction on liver biopsy slides that pathologically confirm the presence of cirrhosis. The presence of cirrhosis must be documented on the liver biopsy report. EXCLUSION Current (within the past 4 weeks) HIV antiviral therapy with other NNRTI's. Concurrent use (within the past 7 days) of any of the following: Systemic azole antifungal agents (fluconazole, itraconazole, ketoconazole, etc.) Clarithromycin Rifampin St John's Wort Inability to provide a blood sample. Patients who have evidence for hepatic or other encephalopathy above Grade 1 Patients with renal failure who require dialysis. Pregnant and/or breast feeding women..

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: nevirapine|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary endpoints are the degree of hepatic impairment, steady state nevirapine clearance, and the increase in estimated clearance when trough is supplemented by plasma levels measured one, two and four hours after nevirapine administration |  | Up to 4 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma levels of nevirapine metabolites of all patients and Child-Pugh scores among patients with cirrhosis. |  | Up to 14 hours |