Evaluation of Kaletra Therapy Over the Long-term

Study Overview
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Brief Summary
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Long term observation of patients under lopinavir/ritonavir containing therapy

Detailed Description
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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.

Official Title
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Evaluation of Kaletra Therapy Over the Long-term

Conditions
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Human Immunodeficiency Virus

Intervention / Treatment
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* Drug: Lopinavir/Ritonavir (Kaletra)


Participation Criteria
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Eligibility Criteria
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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

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 |
| --- | --- |
| therapy-naive<br>Patients who had not received prior antiretroviral drug therapy | Drug: Lopinavir/Ritonavir (Kaletra)<br>* 3 capsules 2xdaily or 2 tablets 2xdaily Kaletra<br>* Other names: Lopinavir/Ritonavir;|
| pre-treated<br>Patients that had previously received antiretroviral therapy, but are protease inhibitor naive | Drug: Lopinavir/Ritonavir (Kaletra)<br>* 3 capsules 2xdaily or 2 tablets 2xdaily Kaletra<br>* Other names: Lopinavir/Ritonavir;|
| non-B<br>Patients infected with non-B subtypes of HIV-1 | Drug: Lopinavir/Ritonavir (Kaletra)<br>* 3 capsules 2xdaily or 2 tablets 2xdaily Kaletra<br>* Other names: Lopinavir/Ritonavir;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Human Immunodeficiency Virus, Infection, Kaletra, Resistance, Mutations, alternative Therapy regimen