Case-Control Viramune (Nevirapine) Toxicogenomics Study

Study Overview
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Brief Summary
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Attempt to identify genetic polymorphisms in interrogated pathways which may be associated with symptomatic hepatotoxicity or severe cutaneous toxicity observed in case patients within the first 8 weeks of nevirapine therapy.

Official Title
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A Case-Control Toxicogenomics Study to Identify Unique Genetic Polymorphisms in Patients Who Have Experienced Symptomatic Hepatotoxicity or Severe Cutaneous Toxicity Within the First 8 Weeks of Nevirapine Therapy

Conditions
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HIV Infections

Intervention / Treatment
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* Drug: Nevirapine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Inclusion for Case Male or female patients >=18 years of age with HIV-1 infection who experienced one or more of the following adverse reactions within the first 8 weeks of starting nevirapine therapy: Grade 3 or 4 LFT elevation (ALT or AST > 5X ULN) and any symptom consistent with clinical hepatitis (see Appendix 10.1) Acute liver failure secondary to nevirapine therapy* Functional group III or IV rash *Acute liver failure is defined as serious liver injury usually requiring hospitalization that may lead to death or liver transplantation. Inclusion for Control Male or female patients >=18 years of age with HIV-1 infection who have been exposed to nevirapine therapy for at least 18 weeks and who do not meet any of the case inclusion criteria Exclusion Criteria: Exclusion for Cases Patients with any hepatotoxicity or rash event which in the investigators judgement is not related to nevirapine use (ex. hepatotoxicity due to alcohol or other medicinal use or rash due to other medicinal use). Patients who began abacavir or TMP-SMX (trimethoprim/sulfamethoxazole) therapy 2 weeks or less prior to or up to 8 weeks after initiating nevirapine therapy. Patients with AST or ALT elevations > 5 times the ULN (>= Grade 3) just prior to the initiation of nevirapine therapy. Exclusion for Controls Patients who discontinued nevirapine before completing 18 weeks of dosing with 200 mg/day for 2 weeks followed by 400 mg/day thereafter. Patients who developed functional group I, IIa or IIb rash within 18 weeks of starting nevirapine therapy, or any dermatologic condition that could plausibly be attributed to nevirapine. Patients with ALT or AST elevations >2.5 X ULN (>Grade 1) within 18 weeks of starting nevirapine therapy. Any hepatobiliary adverse event that could possibly be attributed to nevirapine. Patients who develop any systemic reaction attributable to nevirapine use during the first 18 weeks of nevirapine treatment such as flu-like symptoms, arthralgia, myalgia, or conjunctivitis. Exclusion for Cases and Controls Patients who have participated in the 2NN-Long-term Follow-up study (1100.1454) Patients with CD4 count 150 cells/mm3 prior to the initiation of nevirapine therapy (last available result measured 6 months prior to the initiation of nevirapine therapy). Evidence of acute co-infection with viral hepatitis. Patients taking prednisone, prednisolone, or immuno-modulatory medication within the first 8 weeks of nevirapine therapy. Patients who are unwilling to provide blood samples for DNA testing. Patients who did not sign informed consent and or authorization to release protected health information per local requirements. Patients without available liv

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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| All study population<br> | Drug: Nevirapine<br>* Patients with HIV-1 infection who have taken or are currently taking nevirapine<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Endpoints: relationship between nevirapine-related AEs and genetic polymorphisms loci: Drug metabolizing enzymes (e.g., cytochrome P450 isoforms) Drug transporters (e.g., MDR1 and OATP-C) Human Major Histocompatibility Complex region genes |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Descriptive demographics comparing cases with matched controls in an attempt to link genetic polymorphisms associated with symptomatic hepatotoxicity or severe cutaneous toxicity (cases) to gender, race or other patient characteristics. |  |  |