The patient population for this study will be comprised of patients with HIV-1 infection who have taken or are currently taking nevirapine and who have (cases) or have not (controls) experienced symptom. There will be two matched controls for each case. This study is a non-interventional, retrospective case-controlled (1:2) study with prospective genomic blood sampling.
Conditions
Interventions
Trade Name: Viramune 200 mg Tablets
Product Name: Viramune 200 mg Tablets
Pharmaceutical Form: Tablet
INN or Proposed INN: Nevirapine
Concentration unit: mg milligram(s)
Concentration type: equal
Conc
Sponsors
Boehringer Ingelheim Pharma GmbH & Co. KG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion for Case 1. 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 symptoms consistent with clinical hepatitis (see Appendix 10.1) ?*Acute liver failure secondary to nevirapine therapy ?Functional group III or IV rash (see Appendix 10.2) *Acute liver failure is defined as serious liver injury usually requiring hospitalization that may lead to death or liver transplantation. (MODIFIED: TP AMENDMENT #1) Inclusion for Control 2.Male or female patients =18 years of age with HIV-1 infection who have been exposed to nevirapine therapy and who do not meet any of the case inclusion criteria Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Exclusion for Cases 1. Patients with any hepatotoxicity or rash event which in the investigator’s judgement is not related to nevirapine use (ex. hepatotoxicity due to alcohol or other medicinal use or rash due to other medicinal use). 2. 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. 3. Patients with AST or ALT elevations >5 times the ULN (=Grade 3) just prior to the initiation of nevirapine therapy. (ADDED: TP AMENDMENT #1). Exclusion for Controls 4. Patients who discontinued nevirapine before completing 18 weeks of dosing with 200 mg/day for 2 weeks followed by 400 mg/day thereafter. 5. 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. 6. Patients with ALT or AST elevations >2.5 X ULN (>Grade 1) within 18 weeks of starting nevirapine therapy. (MODIFIED: TP AMENDMENT #1) 7. Any hepatobiliary adverse event that could possibly be attributed to nevirapine. (ADDED: TP AMENDMENT #1) 8. 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 Case and Controls 9. Patients who have participated in the 2NN-Long-term Follow-up study (1100.1454). 10. 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). (ADDED: TP AMENDMENT #3, NUMBERING CORRECTED TP AMENDMENT #4) 11. Evidence of acute co-infection with viral hepatitis. 12. Patients taking prednisone, prednisolone, or immuno-modulatory medication within the first 8 weeks of nevirapine therapy. 13. Patients who are unwilling to provide blood samples for DNA testing. 14. Patients who do not sign informed consent and/or authorization to release protected health information per local requirements. 15. Patients without available liver function test (LFT) results =6 months prior to initiating nevirapine therapy. (ADDED: TP AMENDMENT #3, NUMBERING CORRECTED TP AMENDMENT #4)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Attempt to identify genetic polymorphisms in interrogated candidate genes which may be associated with symptomatic hepatotoxicity or severe cutaneous toxicity observed in case patients within the first 8 weeks of nevirapine therapy. ;Secondary Objective: Descriptive demographics will be utilized to compare 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.;Primary end point(s): The endpoints to be analyzed are the relationship between nevirapine-related adverse events and genetic polymorphisms at the following loci: • Drug metabolizing enzymes (e.g., cytochrome P450 isoforms) • Drug transporters (e.g., MDR1 and OATP-C) • Human Major Histocompatibility Complex (MHC) region genes. | — |
Countries
Germany, United Kingdom
Outcome results
None listed