OK 2004 Study (Only Kaletra 2004 Study): Study to Evaluate Suspending Nucleosides From Triple-Drug Therapy in HIV Subjects

Study Overview
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Brief Summary
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Lopinavir/ritonavir monotherapy may maintain virologic suppression in patients who have been undetectable for six months while on triple drug antiretroviral therapy. Lopinavir/ritonavir pharmacokinetics might prevent resistance development in patients who experience virological rebound after single-drug simplification.

Detailed Description
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Primary Study Objective: Efficacy and durability of switching to lopinavir/ritonavir single-drug HAART compared to maintaining therapy based on lopinavir/ritonavir and two nucleosides Secondary Study Objective(s): Safety (related drug AEs/SAEs and laboratory anomalies G3/4) through 48 w. Resistance profile on patients with sustained virological failure QOL comparing stopping nucleosides versus continuing therapy Pharmaco-economic analysis comparing treatment cost between the 2 study arms. Predicting factors of failure in the stopping nucleosides arm Subject Population: 200 patients Study Design: RANDOMIZATION: Patients are randomized (1:1) either to continue under the same treatment or stop nucleosides as follows: Stopping nucleosides arm: Lopinavir/r alone. Continuing arm: Lopinavir/r + 2 NRTIs STUDY PROCEDURES: A baseline HIV-RNA, CD4 and routine labs will be collected if the most recent results are not collected within the 4 weeks prior entering the study. Patients will be followed for HIV-RNA (and CD4) at w1, w4, w8, w16, w24, w 36 and w48. After w48, durability of response to lopinavir/r single-drug therapy will be studied long-term (up to w96). Routine hematology and clinical chemistry (including fasting triglycerides and cholesterol, total and HDL/LDL ratio) will be measured at w4, w16, w24, w 36 and w48. A central laboratory will be used for HIV-RNA determinations and to archive plasma/cell samples for further genotype test in case of rebound. Treatment adherence will be followed with a self-patient report questionnaire (GEEMA study) All AEs will be collected if suspected relation (possible or probable) to any concomitant ARV drug, and SAEs, related or not, reported within 24h.

Official Title
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Phase III-IV, Comparative, Randomized, Open-Label, Study to Evaluate Safety and Efficacy of Suspending Nucleosides From a Triple-Drug Therapy Based on Lopinavir/Ritonavir Versus Continuing Triple-Drug Therapy in HIV-Infected Subjects With Undetectable Plasma HIV Viremia for Six Months

Conditions
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HIV Infection

Intervention / Treatment
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* Drug: Stopping nucleosides and continuing lopinavir/ritonavir monotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HIV patients > 18 years old who provide signed and dated Informed consent. HIV patients who have been receiving lopinavir/ritonavir and two nucleosides during at least 4 weeks. Plasma HIV RNA < 50 cop/ml for six months Exclusion Criteria: HIV patients who have stopped a protease inhibitor due to virological failure. HIV patients with hepatic or renal insufficiency. HIV patients with positive serum HBVAg HIV patients who require treatment with a lopinavir/r contraindicated medication. HIV pregnant or breastfeeding women. Active drug abuse (including alcohol or recreational drugs). Exception, cannabis, provided the investigator is confident in patient adherence. Patients under Methadone program will be accepted too if deemed appropriate by the investigator.

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

| Intervention/Treatment |
| --- |
|Drug: Stopping nucleosides and continuing lopinavir/ritonavir monotherapy|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| % patients with therapeutic failure in both arms at 48 weeks (OT and ITT) |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| % patients with virological failure: HIV-RNA > 500 cop/ml under the randomly assigned therapy (OT and ITT) |  |  | 
| % patients with HIV RNA < 500 cop/ml and < 50 cop/ml at w24, w48 (OT and ITT) |  |  | 
| Time to virological failure per Kaplan Meyer analysis |  |  | 
| CD4 cell count change from baseline |  |  | 
| Percentage of viruses with resistance in the protease gene at w24 and w48 |  |  | 
| Description of AEs with probable, possible or unknown relationship to study drug |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV, AIDS, Treatment Experienced