Comparison of Treatment Simplification by LPV/r vs Current Treatment Continuation in HIV-Infected Patients

Study Overview
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Brief Summary
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The purpose of this study is to compare the efficacy and tolerance of a treatment simplification by a Lopinavir/ritonavir monotherapy versus continuation of current treatment in HIV-infected patients

Detailed Description
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Highly active antiretroviral therapy (HAART) has made a significant impact on the natural history of HIV-1 infection, but toxicities and complexities of therapy limit long-term efficacy, and make simpler yet effective HAART regimens highly desirable. Previous attempts to 'de-intensify' protease inhibitor (PI)-based therapy by discontinuing reverse transcriptase inhibitors (RTI) after achieving viral suppression met with failure, probably because plasma levels of most individually administered PI are too low to inhibit viral replication consistently. Low-dose ritonavir substantially enhances lopinavir plasma levels, and lopinavir/ritonavir (LPV/r) is effective as part of a combination therapy in both naive and PI-experienced patients. Furthermore, lopinavir is known to have a high genetic barrier to selection of resistance. LPV/r monotherapy could thus have the right combination of potency, favorable pharmacokinetics, and high genetic barrier needed to suppress viral replication and prevent the selection of lopinavir resistance. Preliminary results with maintenanceLPV/r monotherapy show interesting results but data from randomized studies are needed.

Official Title
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A 48-Weeks National Multicenter Randomized Open Clinical Trial Evaluating Tolerance and Efficacy of a Treatment Simplification by Lopinavir/Ritonavir Versus Continuation of Current Treatment in HIV-Infected Patients With a Viral Load Inferior to 50 Copies/mL Since 6 Months At Least

Conditions
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HIV Infections

Intervention / Treatment
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* Drug: Lopinavir/ritonavir (drug)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age > or = 18 years Confirmed HIV-1 seropositivity Antiretroviral treatment stable since 3 months at least HIV-1 ARN load < 50 copies/mL since 6 months at least Signed consent form No history of treatment failure (= viral load > 1000 copies/mL) including a protease inhibitor No opportunistic infection in the previous 6 months Exclusion Criteria: Neutrophils < 750/mm3 Hemoglobin < 8 g/dL Platelets < 60,000/mm3 Creatinin > 150 micromoles/L SGOT > 5 NUL (Normal Upper Limit) SGPT > 5 NUL Current IL-2 treatment HBV infection treated or not by lamivudine or tenofovir Pregnancy or feeding Enrollment in another study not compliant with KALESOLO Study group assignment

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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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Simplification<br>The patients included in this arm are on Monotherapy of Kaletra (Lopinavir/ritonavir)during 48 weeks | Drug: Lopinavir/ritonavir (drug)<br> <br> |
| No Intervention: Continued<br>The patients included in this arm continue their treatment without any changes | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients with a viral load < 50 copies/mL at S48 without any modification of antiretroviral treatment during study |  | W48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Durability of viral response |  | W48 | 
| Evolution of lymphocytes CD4 |  | W48 | 
| Observance |  | W48 | 
| Clinical and biological tolerance |  | W48 | 
| Quantitative and qualitative changes in quality of life data |  | W48 | 
| Cost-efficacy ratio |  | W48 | 
| Predictive value of proviral DNA before treatment simplification |  | W48 | 
| Proportion of patients showing a lipodystrophy at J0 and S48 |  | W48 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV-1, Treatment simplification, Lopinavir/ritonavir, Treatment Experienced, HIV Seropositivity