Fosamprenavir in Pts With Hepatic Impairment

Study Overview
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Brief Summary
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APV10017 was a pharmacokinetic study that evaluated the pharmacokinetics, safety and tolerability of fosamprenavir/ritonavir (FPV/RTV) at reduced doses over 14 days in HIV-infected subjects with mild to moderate hepatic impairment (HI). Based on these data, two new regimens have recently been approved by the EMEA and FDA in these patient groups; FPV 700mg BID/RTV 100mg QD for those with mild HI (Child-Pugh score 4-6) and FPV 450mg BID/RTV 100mg QD for those with moderate HI (Child Pugh score 7-9). The Committee for Medicinal Products for Human Use (CHMP) has requested longer-term safety data among this hepatically impaired HIV-infected population who have received the recently updated FPV/RTV dosing regimens. An observational cohort study will be conducted using routinely collected data in three European HIV patient cohorts with a high proportion of hepatitis co-infected individuals. Patients who received FPV/RTV will be followed to address the following objectives. Primary: To assess the safety and tolerability of FPV/RTV-based ART in subjects with mild to moderate hepatic impairment. Secondary: A). To compare the safety and tolerability of FPV/RTV-based ART in subjects with mild to moderate hepatic impairment when compared to FPV/RTV-based ART in hepatitis B (HBV) or hepatitis C (HCV) co-infected subjects with normal hepatic function. B). To compare the safety and tolerability of FPV/RTV-based ART to lopinavir/ritonavir LPV/RTV-based ART in subjects with mild to moderate hepatic impairment.

Detailed Description
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Patients were not recruited for nor enrolled in this study. This study is a retrospective observational study. Data from medical records or insurance claims databases are anonymised and used to develop a patient cohort. All diagnoses and treatment are recorded in the course of routine medical practice.

Official Title
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HI FPV Study: Using Observational Cohorts to Monitor Safety of Fosamprenavir in Patients With Mild/Moderate Hepatic Impairment

Conditions
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Infection, Human Immunodeficiency Virus

Intervention / Treatment
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* Drug: Intervention A Standard dose
* Drug: Intervention B Reduced Dose
* Drug: Intervention C
* Drug: Intervention D
* Drug: Intervention E


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HIV infected patients with or without hepatic impairment coinfected with HBV or HCV who started FPV/RTV-based therapy on or after January 1, 2008. The FPV/RTV exposed patients will be stratified into four groups for analysis (see interventions A-D for label/description above), according to their degree of baseline hepatic impairment, which will be defined according to FPV/RTV dose received (and APRI score for interventions A and D). The LPV/RTV intervention group must have started this therapy at approved standard doses on or after January 1, 2008. Exclusion Criteria: Receipt of FPV/RTV or LPV/RTV within the year preceding the baseline visit.

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 |
| --- | --- |
| HIV pts w/ HBV or HCV, w/ or w/o mild to moderate HI<br>Patients with HIV coinfected with HBV or HCV with or without mild to moderate HI who are enrolled in one of the participating HIV patient cohorts. These patients will be exposed to FPV/RTV or LPV/RTV. | Drug: Intervention A Standard dose<br>* HIV subjects with HBV or HCV co-infection but normal hepatic function, defined by receipt of FPV 700mg BID/RTV 100mg BID and a baseline AST-platelet ratio index (APRI) score of <2.0.<br>Drug: Intervention B Reduced Dose<br>* HIV subjects with mild hepatic impairment, defined by receipt of the recommended reduced FPV/RTV dose (700mg BID/100mg QD).<br>Drug: Intervention C<br>* HIV subjects with moderate hepatic impairment, defined by receipt of FPV 450mg BID/RTV 100mg QD.<br>Drug: Intervention D<br>* HIV subjects receiving the standard dose of FPV/RTV despite evidence of abnormal hepatic function according to APRI score: HIV subjects with HBV or HCV co-infection, receipt of FPV 700mg BID/RTV 100mg BID and a baseline APRI score of ≥2.0.<br>Drug: Intervention E<br>* HIV subjects coinfected with HBV or HCV who have initiated standard doses of LPV 400mg/RTV 100mg and enrolled in the same cohorts as the FPV/RTV exposed subjects.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Events of ALT Elevation After Baseline, Controlling for APRI Score and Other Variables | An elevation in ALT is defined as a single value >200 IU/I. | The incidence of these events was assessed over time during Year 1, censoring participants' follow-up at date of last ALT | 
| Number of Events of an Elevation in ALT After Baseline by Treatment Group, Controlling for APRI-score, and Other Variables | An elevation in ALT is defined as a single value >200 IU/I. | Incidence of these events was assessed over time during Year 1, censoring patients' follow-up at date of last ALT | 
| Number of Events of an Elevation in ALT After Baseline by Treatment Group, Controlling for FIB-score, and Other Variables | An elevation in ALT is defined as a single value >200 IU/I. | Incidence was assessed over time during Year 1 | 
| Number of Events of an Elevation in ALT After Baseline by Treatment Group, Controlling for Current Values of CD4 and Platelet Counts | An elevation in ALT is defined as a single value >200 IU/I. | Incidence was assessed over time during Year 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Events of First Discontinuation of FPV/RTV or LPV/RTV Alone by Treatment Group, Controlling for APRI-score, and Other Variables | A first discontinuation is defined as the first occurrence of stopping FPV/RTV or LPV/RTV. | Incidence was assessed over time during Year 1 | 
| Number of Events of First Discontinuation of FPV/RTV or LPV/RTV Alone by Treatment Group, Controlling for FIB-score, and Other Variables | A first discontinuation is defined as the first occurrence of stopping FPV/RTV or LPV/RTV. | Incidence was assessed over time during Year 1 | 
| Number of Events of First Discontinuation of FPV/RTV- or LPV/RTV Alone by Treatment Group, Controlling for Current Values of CD4 and Platelet Counts | A first discontinuation is defined as the first occurrence of stopping FPV/RTV or LPV/RTV | Incidence was assessed over time during Year 1 | 
| Number of Events of First Discontinuation of FPV/RTV or LPV/RTV Alone Due to Adverse Events Only | A first discontinuation is defined as the first occurrence of stopping FPV/RTV or LPV/RTV; where the reason for stopping is attritubed to adverse events only | Incidence was assessed over time during Year 1 | 
| Number of Events of First Discontinuation of One or More Drugs Included in the FPV/RTV- or LPV/RTV-based Regimen by Treatment Group, Controlling for APRI-score and Other Variables (See Comments) | A first discontinuation is defined as the first occurrence of stopping one or more drugs in the FPV/RTV or LPV/RTV-based regime | Incidence was assessed over time during Year 1 | 
| Number of Events of First Discontinuation of One or More Drugs Included in the FPV/RTV- or LPV/RTV-based Regimen by Treatment Group, Controlling for FIB-score and Other Variables | A first discontinuation is defined as the first occurrence of stopping one or more drugs in the FPV/RTV or LPV/RTV-based regime. | Incidence was assessed over time during Year 1 | 
| Number of Events of First Discontinuation of One or More Drugs Included in the FPV/RTV- or LPV/RTV-based Regimen by Treatment Group, Controlling Current Values of CD4 and Platelet Counts | A first discontinuation is defined as the first occurrence of stopping one or more drugs in the FPV/RTV or LPV/RTV-based regime. | Incidence was assessed over time during Year 1 | 
| Number of Events of Discontinuation of One or More Drugs in the FPV/RTV- or LPV/RTV Regimen Due to Adverse Events Only | Defined as the occurrence of stopping FPV/RTV or LPV/RTV; where the reason for stopping is attributed to adverse events only | Incidence was assessed over time during Year 1 | 
| Number of Events of First Discontinuation of FPV/RTV or LPV/RTV Alone Due to the Indicated Adverse Events | Defined as the first occurrence of stopping FPV/RTV or LPV/RTV; where the reason for stopping is attributed to adverse events only. Adverse events can only be attributed to the body system stated (no further specificity is available). | Incidence was assessed over time during Year 1 | 
| Number of Participants Who Discontinued the Indicated Antiretrovirals for the First Time After Starting FPV/r or LPV/r | Antiretrovirals discontinued for the first time after starting FPV/r or LPV/r | Assessed over time during Year 1 | 
| Number of Participants With the Indicated Major Reasons for Discontinuing One or More Drugs in the FPV/r or LPV/r Regimen | Major reasons for discontinuing one or more drugs in the FPV/r or LPV/r regimen | Assessed over time during Year 1 | 
| Number of Participants for Which the Reason for Discontinuation of One or More Drugs in the FPV/RTV or LPV/RTV Regimen Was Due to Adverse Events Only | Number of participants for which the reason for discontinuation of one or more drugs in the FPV/RTV or LPV/RTV regimen was due to adverse events only. Adverse events can only be attributed to the body system stated (no further specificity is available) | The incidence of these events was assessed over time during Year 1 | 
| Incidence Rates Per 100 Person-years of Follow-up (PYFU) of Study Main Outcome Measures | Incidence rates per 100 person-years of follow-up of study primary outcome. The numbers analyzed in the category titles represent the number of patients with each event. Incidence rate is the number of new cases per population in a given time period, where the denominator is the sum of the person-time of the at-risk population. | Incidence of these events was assessed over time during Year 1 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV, antiretroviral therapy, hepatic impairment