Kaletra in Combination With Antiretroviral Agents (PROTEKT)

KALETRA in Combination With New Substances (PROTEKT)

The purpose of this study is to investigate the tolerability of Kaletra (lopinavir/ritonavir) in combination with new substances such as integrase inhibitors (INIs), C-C chemokine receptor type 5 (CCR5) antagonists, and new non-nucleoside reverse transcriptase inhibitors (NNRTIs), as there are many reasons (intolerability, complex resistant patterns or even personal reasons) which may result in a change from the daily clinical routine and lead to the use of a newly approved antiretroviral agent in combination with Kaletra.

Study Overview

• Status: Completed
• Conditions: Human Immunodeficiency Virus

Detailed Description

This study was designed as a non-interventional observational study. Kaletra was prescribed in the usual manner in accordance with the terms of the local market authorization with regards to dose, population and indication as well as local guidelines.

• Study Type: Observational
• Enrollment (Actual): 502

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Community sample: HIV-positive patients

Description

Inclusion Criteria:

• Patients ≥ 18years of age
• Written informed consent (authorization to the investigator to use and/or disclose personal and/or health data before entry into the KALETRA® post marketing observational study)
• HIV-1 infection
• Patients treated with KALETRA®, independent from their participation in this study
• Patients treated with novel antiretroviral therapy (for at least 8 weeks according to the study amendment), independent from their participation in this study

Exclusion Criteria:

• Hypersensitivity against Kaletra or other ingredients or INIs or NNRTIs or CCR5 antagonists
• Severe liver insufficiency
• No concommitant astemizole, terfenadine, oral midazolam, triazolam, cisapride, pimozide, amiodarone, ergotamine, dihydroergotamine, ergometrine, methylergometrine, vardenafil and/or St. John's wort

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Human Immunodeficiency Virus (HIV)-Infected Participants; HIV-infected participants on Kaletra and INIs or NNRTIs or CCR5 antagonists

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevalence of Adverse Events (Weeks 0-144), Per Event	Percentage of overall number of adverse events experienced during Weeks 0-144 by adverse event type. Doctors asked participants for adverse events, grouped them into categories given in the electronic case report form (eCRF). The list of adverse events included in the eCRF were hypertriglyceridemia, hypercholesterolemia, low high density lipoprotein (HDL) cholesterol, high low density lipoprotein (LDL) cholesterol, hyperglycemia, hyperbilirubinemia, elevated aspartate aminotransferase (AST), elevated alanine aminotransferase (ALT), elevated gamma glutamyl transferase (γGT), elevated alkaline phosphatase, stomatitis, nausea, vomiting, diarrhea, abdominal pain, mood disorder, neurocerebellar disorder, headache, fatigue, fever, other (listed as 'not specified').	Weeks 0 to 144
Prevalence of Adverse Events (Weeks 0-144), Per Participant	Percentage of participants who experienced at least 1 adverse event during Weeks 0-144 by adverse event type. Doctors asked participants for adverse events, grouped them into categories given in the eCRF. The list of adverse events included in the eCRF were hypertriglyceridemia, hypercholesterolemia, low HDL cholesterol, high LDL cholesterol, hyperglycemia, hyperbilirubinemia, elevated AST, elevated ALT, elevated γGT, elevated alkaline phosphatase, stomatitis, nausea, vomiting, diarrhea, abdominal pain, mood disorder, neurocerebellar disorder, headache, fatigue, fever, other (listed as 'not specified').	Weeks 0 to 144

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Absolute Cluster of Differentiation 4 (CD4) Cell Count	Changes in participants' CD4 cell counts were assessed by measuring the change from Baseline in the number of CD4 cells at scheduled visits planned as part of routine care.	Baseline (Week 0) to Week 144
Percentage of Participants Achieving Absolute CD4 Cell Count Increases From Baseline of ≥ 100 Cells/μL at All Time Points, Modified Intent-to-Treat Analysis	Changes in participants' CD4 cell counts were assessed by measuring the number of CD4 cells at scheduled visits planned as part of routine care.	Baseline (Week 0) to Week 144
Percentage of Participants Achieving Absolute CD4 Cell Count Increases From Baseline of ≥ 100 Cells/μL at All Time Points, As Treated Analysis	Changes in participants' CD4 cell counts were assessed by measuring the number of CD4 cells at scheduled visits planned as part of routine care.	Baseline (Week 0) to Week 144
Time to CD4 Cell Count Increase From Baseline of ≥ 100/ Cells/μL		From Week 0 to Week 144
Number of Participants With Lopinavir (LPV) Resistance at Baseline	Characterization of baseline resistance and development of resistance using the interpretation system HIV-Genotypic Resistance-Algorithm Deutschland (GRADE; available at www.hiv-grade.de. Genotypic interpretation was performed using the HIV-GRADE algorithm updated in December 2015). "Susceptible" indicates full susceptibility of a virus to a certain drug without any limitations in terms of resistance. "Partial" resistance is indicated if severe limitations in susceptibility have to be expected and the drug can not count for a fully active drug any more. However, these drugs can still be very useful in situations with generally limited options (salvage). "Resistant" indicates that high level drug resistance has to be expected.	Baseline (Week 0)
Number of Participants With LPV Resistance During Follow-Up	Characterization of baseline resistance and development of resistance using the interpretation system HIV-GRADE (available at www.hiv-grade.de. Genotypic interpretation was performed using the HIV-GRADE algorithm updated in December 2015). "Susceptible" indicates full susceptibility of a virus to a certain drug without any limitations in terms of resistance. "Partial" resistance is indicated if severe limitations in susceptibility have to be expected and the drug can not count for a fully active drug any more. However, these drugs can still be very useful in situations with generally limited options (salvage). "Resistant" indicates that high level drug resistance has to be expected.	up to Week 144
Number of Participants With Protease Inhibitor (PI) Resistance at Baseline	Characterization of baseline resistance and development of resistance using the interpretation system HIV-Genotypic Resistance-Algorithm Deutschland (GRADE; available at www.hiv-grade.de. Genotypic interpretation was performed using the HIV-GRADE algorithm updated in December 2015). "Susceptible" indicates full susceptibility of a virus to a certain drug without any limitations in terms of resistance. "Partial" resistance is indicated if severe limitations in susceptibility have to be expected and the drug can not count for a fully active drug any more. However, these drugs can still be very useful in situations with generally limited options (salvage). "Resistant" indicates that high level drug resistance has to be expected.	Baseline (Week 0)
Number of Participants With PI Resistance During Follow-Up	Characterization of baseline resistance and development of resistance using the interpretation system HIV-GRADE (available at www.hiv-grade.de. Genotypic interpretation was performed using the HIV-GRADE algorithm updated in December 2015). "Susceptible" indicates full susceptibility of a virus to a certain drug without any limitations in terms of resistance. "Partial" resistance is indicated if severe limitations in susceptibility have to be expected and the drug can not count for a fully active drug any more. However, these drugs can still be very useful in situations with generally limited options (salvage). "Resistant" indicates that high level drug resistance has to be expected.	Up to Week 144
Number of Participants With INI Resistance at Baseline	Characterization of baseline resistance and development of resistance using the interpretation system HIV-GRADE (available at www.hiv-grade.de. Genotypic interpretation was performed using the HIV-GRADE algorithm updated in December 2015). "Susceptible" indicates full susceptibility of a virus to a certain drug without any limitations in terms of resistance. "Partial" resistance is indicated if severe limitations in susceptibility have to be expected and the drug can not count for a fully active drug any more. However, these drugs can still be very useful in situations with generally limited options (salvage). "Resistant" indicates that high level drug resistance has to be expected.	Baseline (Week 0)
Number of Participants With INI Resistance During Follow-Up	Characterization of baseline resistance and development of resistance using the interpretation system HIV-GRADE (available at www.hiv-grade.de. Genotypic interpretation was performed using the HIV-GRADE algorithm updated in December 2015). "Susceptible" indicates full susceptibility of a virus to a certain drug without any limitations in terms of resistance. "Partial" resistance is indicated if severe limitations in susceptibility have to be expected and the drug can not count for a fully active drug any more. However, these drugs can still be very useful in situations with generally limited options (salvage). "Resistant" indicates that high level drug resistance has to be expected.	up to Week 144
Number of Participants With NNRTI Resistance at Baseline	Characterization of baseline resistance and development of resistance using the interpretation system HIV-GRADE (available at www.hiv-grade.de. Genotypic interpretation was performed using the HIV-GRADE algorithm updated in December 2015). "Susceptible" indicates full susceptibility of a virus to a certain drug without any limitations in terms of resistance. "Partial" resistance is indicated if severe limitations in susceptibility have to be expected and the drug can not count for a fully active drug any more. However, these drugs can still be very useful in situations with generally limited options (salvage). "Resistant" indicates that high level drug resistance has to be expected.	Baseline (Week 0)
Number of Participants With NNRTI Resistance During Follow-Up	Characterization of baseline resistance and development of resistance using the interpretation system HIV-GRADE (available at www.hiv-grade.de. Genotypic interpretation was performed using the HIV-GRADE algorithm updated in December 2015). "Susceptible" indicates full susceptibility of a virus to a certain drug without any limitations in terms of resistance. "Partial" resistance is indicated if severe limitations in susceptibility have to be expected and the drug can not count for a fully active drug any more. However, these drugs can still be very useful in situations with generally limited options (salvage). "Resistant" indicates that high level drug resistance has to be expected.	up to Week 144
Number of Participants With Nucleoside Analog Reverse-Transcriptase Inhibitor (NRTI) Resistance at Baseline	Characterization of baseline resistance and development of resistance using the interpretation system HIV-GRADE (available at www.hiv-grade.de. Genotypic interpretation was performed using the HIV-GRADE algorithm updated in December 2015). "Susceptible" indicates full susceptibility of a virus to a certain drug without any limitations in terms of resistance. "Partial" resistance is indicated if severe limitations in susceptibility have to be expected and the drug can not count for a fully active drug any more. However, these drugs can still be very useful in situations with generally limited options (salvage). "Resistant" indicates that high level drug resistance has to be expected.	Baseline (Week 0)
Number of Participants With NRTI Resistance During Follow-Up	Characterization of baseline resistance and development of resistance using the interpretation system HIV-GRADE (available at www.hiv-grade.de. Genotypic interpretation was performed using the HIV-GRADE algorithm updated in December 2015). "Susceptible" indicates full susceptibility of a virus to a certain drug without any limitations in terms of resistance. "Partial" resistance is indicated if severe limitations in susceptibility have to be expected and the drug can not count for a fully active drug any more. However, these drugs can still be very useful in situations with generally limited options (salvage). "Resistant" indicates that high level drug resistance has to be expected.	up to Week 144
Number of Participants With HIV-1 Coreceptor Tropism at Baseline	Participants with CCR5 tropic virus, CXC motif chemokine receptor 4 (CRCX4) tropic virus, or dual/mixed tropic virus at Baseline.	Baseline (Week 0)
Number of Participants With HIV-1 Coreceptor Tropism During Follow-up	Participants with CCR5 tropic virus, CXC motif chemokine receptor 4 (CRCX4) tropic virus, or dual/mixed tropic virus at Follow-up.	up to Week 144

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in HIV-1 Ribonucleic Acid (RNA) Viral Load	Changes in participants' HIV-1 RNA viral load were assessed by measuring the change from Baseline at scheduled visits planned as part of routine care.	Baseline (Week 0) to Week 144
Time to Virologic Failure	Time to virologic failure was defined by the earliest occurrence of: HIV-1 RNA > 400 copies/mL confirmed on 2 consecutive occasions after achieving at least 1 HIV-1 RNA < 50 copies/mL,; HIV-1 RNA > 400 copies/mL at the final on-study visit if the participant had previously experienced at least 1 HIV-1 RNA < 50 copies/mL but subsequently did not have HIV-1 RNA > 400 copies/mL on 2 consecutive occasions, or; Day 1 if the participant never achieved HIV-1 RNA < 50 copies/mL during study participation. A participant who prematurely discontinued study drug with HIV-1 RNA < 50 copies/mL was censored from analysis at the time of discontinuation provided that he/she did not previously experience either (a), (b) or (c).	Baseline (Week 0) to Week 144

Collaborators and Investigators

• Sponsor: AbbVie (prior sponsor, Abbott)
• Investigators: Study Director: Bianca Wittig, MD, AbbVie Deutschland GmbH & Co. KG, Medical Department

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: September 1, 2008
• Primary Completion (Actual): January 1, 2016
• Study Completion (Actual): January 1, 2016

Study Registration Dates

• First Submitted: February 24, 2010
• First Submitted That Met QC Criteria: February 24, 2010
• First Posted (Estimate): February 26, 2010

Study Record Updates

• Last Update Posted (Actual): May 19, 2017
• Last Update Submitted That Met QC Criteria: May 18, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: Infection; Human Immunodeficiency Virus; Kaletra; Etravirine; Rilpivirine; CCR5 antagonists; Maraviroc; Safety and efficacy; Non nucleoside reverse transcriptase inhibitors (NNRTIs); Integrase inhibitors; Raltegravir
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immune System Diseases; Slow Virus Diseases; HIV Infections; Acquired Immunodeficiency Syndrome; Immunologic Deficiency Syndromes
• Other Study ID Numbers: P11-021

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No