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.
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.
Study Type
OBSERVATIONAL
Enrollment
167
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.
HIV subjects with mild hepatic impairment, defined by receipt of the recommended reduced FPV/RTV dose (700mg BID/100mg QD).
HIV subjects with moderate hepatic impairment, defined by receipt of FPV 450mg BID/RTV 100mg QD.
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.
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.
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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 APRI-score, and Other Variables
A first discontinuation is defined as the first occurrence of stopping FPV/RTV or LPV/RTV.
Time frame: 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.
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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.
Time frame: 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.
Time frame: 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
Time frame: 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).
Time frame: 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
Time frame: 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
Time frame: 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)
Time frame: 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.
Time frame: Incidence of these events was assessed over time during Year 1
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