Kaletra in Combination With Antiretroviral Agents

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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KALETRA in Combination With New Substances (PROTEKT)

Conditions
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Human Immunodeficiency Virus

Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 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 |
| --- | --- |
| Human Immunodeficiency Virus (HIV)-Infected Participants<br>HIV-infected participants on Kaletra and INIs or NNRTIs or CCR5 antagonists | |

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Infection, Rilpivirine, CCR5 antagonists, Etravirine, Human Immunodeficiency Virus, Maraviroc, Safety and efficacy, Non nucleoside reverse transcriptase inhibitors (NNRTIs), Integrase inhibitors, Raltegravir, Kaletra