Evaluation of Kaletra Therapy Over the Long-term

Long term observation of patients under lopinavir/ritonavir containing therapy

Study Overview

• Status: Completed
• Conditions: Human Immunodeficiency Virus
• Intervention / Treatment: Drug: Lopinavir/Ritonavir (Kaletra)

Detailed Description

Three to five year observation of lopinavir/ritonavir therapy. Reporting groups are 1) therapy-naïve patients (144 weeks), 2) therapy-experienced but protease inhibitor naïve patients (240 weeks,) and 3) non-B subtype infected patients (240 weeks).

These three groups of participants with HIV-1 infection were at first registered as three different studies: KAL1RO (this study, NCT01083810, n=137), KAL2RO /KAL5RO (NCT01083836, n=92), and KAL6RO (NCT01081470, n=55) but were now reconciled under KAL1RO (NCT01083810) as a single study with three reporting groups.

• Study Type: Observational
• Enrollment (Actual): 284

Contacts and Locations

Study Locations

• Germany
  • Aachen, Germany, 52062
    • Site Ref # / Investigator 27706
  • Aachen, Germany, 52062
    • Site Ref # / Investigator 52972
  • Berlin, Germany, 10117
    • Site Ref # / Investigator 27660
  • Berlin, Germany, 10117
    • Site Ref # / Investigator 27937
  • Berlin, Germany, 10117
    • Site Ref # / Investigator 52973
  • Berlin, Germany, 10243
    • Site Reference ID/Investigator# 27629
  • Berlin, Germany, 10439
    • Site Ref # / Investigator 27651
  • Berlin, Germany, 10439
    • Site Ref # / Investigator 27912
  • Berlin, Germany, 10439
    • Site Reference ID/Investigator# 27544
  • Berlin, Germany, 10551
    • Site Reference ID/Investigator# 27567
  • Berlin, Germany, 10589
    • Site Ref # / Investigator 27929
  • Berlin, Germany, 10707
    • Site Ref # / Investigator 52971
  • Berlin, Germany, 10707
    • Site Ref # / Investigator 53468
  • Berlin, Germany, 10777
    • Site Ref # / Investigator 27965
  • Berlin, Germany, 10777
    • Site Reference ID/Investigator# 27547
  • Berlin, Germany, 10777
    • Site Reference ID/Investigator# 27552
  • Berlin, Germany, 10777
    • Site Reference ID/Investigator# 27562
  • Berlin, Germany, 10961
    • Site Ref # / Investigator 52984
  • Berlin, Germany, 13347
    • Site Ref # / Investigator 27639
  • Berlin, Germany, 13347
    • Site Ref # / Investigator 52970
  • Berlin, Germany, D-10243
    • Site Ref # / Investigator 27909
  • Berlin, Germany, D-10243
    • Site Ref # / Investigator 47113
  • Chemnitz, Germany, 09113
    • Site Reference ID/Investigator# 27574
  • Cologne, Germany, 50674
    • Site Ref # / Investigator 28060
  • Cologne, Germany, 50674
    • Site Ref # / Investigator 52978
  • Cologne, Germany, 50679
    • Site Ref # / Investigator 27932
  • Cologne, Germany, 50679
    • Site Ref # / Investigator 52979
  • Cologne, Germany, 50931
    • Site Ref # / Investigator 48233
  • Cologne, Germany, 50931
    • Site Ref # / Investigator 52985
  • Cologne, Germany, 50931
    • Site Ref # / Investigator 53464
  • Dortmund, Germany, 44137
    • Site Ref # / Investigator 27704
  • Dortmund, Germany, 44137
    • Site Ref # / Investigator 27947
  • Dortmund, Germany, 44137
    • Site Ref # / Investigator 52968
  • Duesseldorf, Germany, 40237
    • Site Ref # / Investigator 28056
  • Duisburg, Germany, 47259
    • Site Reference ID/Investigator# 27558
  • Frankfurt, Germany, 15232
    • Site Ref # / Investigator 52983
  • Frankfurt, Germany, 60311
    • Site Ref # / Investigator 27928
  • Frankfurt, Germany, 60311
    • Site Ref # / Investigator 52967
  • Freiburg, Germany, 79106
    • Site Reference ID/Investigator# 27565
  • Fuerth, Germany, 90762
    • Site Reference ID/Investigator# 27566
  • Fuerth, Germany, D-90762
    • Site Ref # / Investigator 53465
  • Hamburg, Germany, 20099
    • Site Ref # / Investigator 27931
  • Hamburg, Germany, 20099
    • Site Ref # / Investigator 27982
  • Hamburg, Germany, 20099
    • Site Ref # / Investigator 47114
  • Hamburg, Germany, 20099
    • Site Ref # / Investigator 47115
  • Hamburg, Germany, 20099
    • Site Reference ID/Investigator# 27551
  • Hamburg, Germany, 20099
    • Site Reference ID/Investigator# 27634
  • Hamburg, Germany, 20146
    • Site Ref # / Investigator 30864
  • Hamburg, Germany, 20146
    • Site Ref # / Investigator 5348
  • Hamburg, Germany, 20146
    • Site Reference ID/Investigator# 27546
  • Hamburg, Germany, 20246
    • Site Ref # / Investigator 28032
  • Hamburg, Germany, 20246
    • Site Ref # / Investigator 52969
  • Hamburg, Germany, 20246
    • Site Ref # / Investigator 53467
  • Hamburg, Germany, 20354
    • Site Ref # / Investigator 52980
  • Karlsruhe, Germany, 76135
    • Site Ref # / Investigator 27641
  • Karlsruhe, Germany, 76135
    • Site Ref # / Investigator 27964
  • Karlsruhe, Germany, 76135
    • Site Reference ID/Investigator# 27561
  • Koblenz, Germany, 56065
    • Site Ref # / Investigator 53466
  • Koblenz, Germany, 56065
    • Site Reference ID/Investigator# 27555
  • Krefeld, Germany, 47800
    • Site Ref # / Investigator 27905
  • Leipzig, Germany, 04107
    • Site Ref # / Investigator 27906
  • Leipzig, Germany, 04107
    • Site Ref # / Investigator 52975
  • Leipzig, Germany, 04107
    • Site Ref # / Investigator 53463
  • Ludwigshafen, Germany, 67063
    • Site Ref # / Investigator 27948
  • Ludwigshafen, Germany, 67063
    • Site Ref # / Investigator 52977
  • Mainz, Germany, 55116
    • Site Ref # / Investigator 27902
  • Mainz, Germany, 55116
    • Site Reference ID/Investigator# 27543
  • Moenchengladbach, Germany, 41061
    • Site Ref # / Investigator 28104
  • Moenchengladbach, Germany, 41061
    • Site Ref # / Investigator 52981
  • Muenster, Germany, 48149
    • Site Ref # / Investigator 27648
  • Muenster, Germany, 48149
    • Site Reference ID/Investigator# 27568
  • Munich, Germany, 80337
    • Site Ref # / Investigator 27949
  • Munich, Germany, 80337
    • Site Reference ID/Investigator# 27553
  • Munich, Germany, 80801
    • Site Ref # / Investigator 27926
  • Munich, Germany, 80801
    • Site Ref # / Investigator 53462
  • Nuernberg, Germany, 90419
    • Site Ref # / Investigator 52982
  • Oldenburg, Germany, 26121
    • Site Ref # / Investigator 27988
  • Oldenburg, Germany, 26121
    • Site Reference ID/Investigator# 27563
  • Osnabrueck, Germany, 49076
    • Site Ref # / Investigator 27637
  • Osnabrueck, Germany, 49076
    • Site Ref # / Investigator 27943
  • Osnabrueck, Germany, 49076
    • Site Ref # / Investigator 52974
  • Paderborn, Germany, 33100
    • Site Ref # / Investigator 27939
  • Rostock, Germany, 18057
    • Site Ref # / Investigator 27649
  • Rostock, Germany, D-18057
    • Site Reference ID/Investigator# 27569
  • Stuttgart, Germany, 70197
    • Site Ref # / Investigator 27647
  • Stuttgart, Germany, 70197
    • Site Ref # / Investigator 28047
  • Stuttgart, Germany, 70197
    • Site Ref # / Investigator 28048
  • Stuttgart, Germany, 70197
    • Site Reference ID/Investigator# 27631
  • Troisdorf, Germany, 53840
    • Site Ref # / Investigator 52976
  • Wuppertal, Germany, 42277
    • Site Ref # / Investigator 27961

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Human Immunodeficiency Virus-infected, protease inhibitor-naïve patients from a clinical setting

Description

Inclusion Criteria:

• Patients infected by HIV-1
• Age greater than or equal to 18 years

Exclusion Criteria:

• as described in SmPC (summary of product characteristics) at the time of prescription

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
therapy-naive; Patients who had not received prior antiretroviral drug therapy	Drug: Lopinavir/Ritonavir (Kaletra); 3 capsules 2xdaily or 2 tablets 2xdaily Kaletra; Other Names: Kaletra; Lopinavir/Ritonavir; ABT-378/r
pre-treated; Patients that had previously received antiretroviral therapy, but are protease inhibitor naive	Drug: Lopinavir/Ritonavir (Kaletra); 3 capsules 2xdaily or 2 tablets 2xdaily Kaletra; Other Names: Kaletra; Lopinavir/Ritonavir; ABT-378/r
non-B; Patients infected with non-B subtypes of HIV-1	Drug: Lopinavir/Ritonavir (Kaletra); 3 capsules 2xdaily or 2 tablets 2xdaily Kaletra; Other Names: Kaletra; Lopinavir/Ritonavir; ABT-378/r

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Patients With Virus That Develop Mutations Conferring Resistance to Lopinavir/Ritonavir, NRTIs or NNRTIs	Standard genotypic resistance assays were developed for HIV-1 viral load levels greater than 500 to 1000 copies per milliliter (mL). All 3 protocols recommended this testing be done at Baseline prior to lopinavir/ritonavir therapy and (if possible) in cases of virologic failure. The exact timing varied and depended on whether there was an adequate viral load and physician clinical judgment. Participants with resistance to lopinavir/ritonavir, nucleoside reverse transcriptase inhibitors (NRTI) or non-nucleoside reverse transcriptase inhibitors (NNRTI) at Baseline and follow-up are reported.	Baseline and at any timepoint where testing is possible

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Patients With HIV-1 RNA <50 Copies/ml	All 3 protocols recommended that HIV viral load tests be performed at Baseline and each study visit. Study visits were to occur at approximately Weeks 4, 12, and 24, followed by 12-week intervals up to Week 144 in therapy-naive participants and up to Week 240 in the pre-treated and non-B subtype groups. The percentage of participants with HIV-1 ribonucleic acid (RNA) less than 50 copies/mL at each time point is presented by subgroup.	Baseline, Week 4, 12, 24, followed by 12-week intervals up to 144/240 weeks
Percentage of Patients With HIV-1 RNA 50 to <200 Copies/ml	All 3 protocols recommended that HIV viral load tests be performed at Baseline and each study visit. Study visits were to occur at approximately Weeks 4, 12, and 24, followed by 12-week intervals up to Week 144 in therapy-naive participants and up to Week 240 in the pre-treated and non-B subtype groups. The percentage of participants with HIV-1 RNA levels of 50 to less than 200 copies/mL at each time point is presented by subgroup.	Baseline, Week 4, 12, 24, followed by 12-week intervals up to 144/240 weeks
Percentage of Patients With HIV-1 RNA 200 to <500 Copies/ml	All 3 protocols recommended that HIV viral load tests be performed at Baseline and each study visit. Study visits were to occur at approximately Weeks 4, 12, and 24, followed by 12-week intervals up to Week 144 in therapy-naive participants and up to Week 240 in the pre-treated and non-B subtype groups. The percentage of participants with HIV-1 RNA levels of 200 to less than 500 copies/mL at each time point is presented by subgroup.	Baseline, Week 4, 12, 24, followed by 12-week intervals up to 144/240 weeks
Percentage of Patients With HIV-1 RNA >500 Copies/ml	All 3 protocols recommended that HIV viral load tests be performed at Baseline and each study visit. Study visits were to occur at approximately Weeks 4, 12, and 24, followed by 12-week intervals up to Week 144 in therapy-naive participants and up to Week 240 in the pre-treated and non-B subtype groups. The percentage of participants with more than 500 HIV-1 RNA copies/mL at each time point is presented by subgroup.	Baseline, Week 4, 12, 24, followed by 12-week intervals up to 144/240 weeks
Change in Absolute CD4 Cell Count [CD4+ Cells/µL]	The evolution of participants' CD4-positive (CD4+) T-lymphocyte counts after starting the lopinavir/ritonavir-containing regimen was to be assessed by measuring the number of CD4+ cells at baseline and each subsequent study visit. Study visits were to occur at approximately Weeks 4, 12, 24, followed by 12-week intervals up to Week 144 in therapy-naive participants and up to Week 240 in the pre-treated and non-B subtype groups. CD4+ cell count results are reported as the change from Baseline in the absolute number of CD4+ cells per microliter.	Baseline, Week 4, 12, 24, followed by 12-week intervals up to 144/240 weeks

Collaborators and Investigators

• Sponsor: Abbott

Study record dates

Study Major Dates

• Study Start: June 1, 2001
• Primary Completion (Actual): June 1, 2010
• Study Completion (Actual): June 1, 2010

Study Registration Dates

• First Submitted: February 26, 2010
• First Submitted That Met QC Criteria: March 8, 2010
• First Posted (Estimate): March 10, 2010

Study Record Updates

• Last Update Posted (Estimate): August 11, 2011
• Last Update Submitted That Met QC Criteria: August 9, 2011
• Last Verified: August 1, 2011

More Information

Terms related to this study

• Keywords: Infection; Human Immunodeficiency Virus; Resistance; Kaletra; Mutations; alternative Therapy regimen
• 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; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Ritonavir; Lopinavir
• Other Study ID Numbers: KAL 1 RO