Raltegravir Switch for Toxicity or Adverse Events

Study Overview
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Brief Summary
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This study aims to verify the persistent control of the virus replication at 48 weeks after the simplification to tenofovir + emtricitabine + raltegravir or to lamivudine+abacavir+raltegravir in patients with optimal virological suppression without any virological failure to previous combined antiretroviral therapies needing a therapeutic switch for toxicity related issues or adverse events.

Official Title
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Phase IIb Pilot Study for the Evaluation of the Safety and the Feasibility of Treatment Simplification to Tenofovir+Emtricitabine+Raltegravir or to Lamivudine+Abacavir+Raltegravir in Patients With Optimal Virological Control and Toxicity to the Current Combined Antiretroviral Regimen

Conditions
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HIV/AIDS, Antiretroviral Therapy, HIV Infections

Intervention / Treatment
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* Drug: tenofovir emtricitabine raltegravir
* Drug: Lamivudine Abacavir Raltegravir
* Drug: Abacavir free


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients treated with a combined antiretroviral therapy from at least 1 year Aged 18 years or older With one or more of the following conditions: Grade 3 or 4 Dyslipidemia Any Hyperglycemia Lipodystrophy (patient's self report, confirmed by physician's physical examination) Moderate/severe cardiovascular risk, defined as a calcium score higher than 40 or a Framingham score higher than 10 (estimated 10 years cardiovascular risk: 10%) Diarrhea (at least 3 emissions of loose stool every day for at least 3 days every week) With at least two HIV-RNA levels <50 copies/mL on two consecutive determinations at least 3 months apart With CD4 cell count >200 cells/ μL for at least 6 months and absence of any opportunistic infection or AIDS-related disease during the last year before screening. Who gave informed consent to the participation to the study Exclusion Criteria: Pregnancy or breast feeding, desire of pregnancy in the short term Previous virological failure (two consecutive HIV-RNA levels > 50 copies/mL or a single value >1000 copies/mL) to antiretroviral therapy and/or previous exposure to mono- or dual therapies with reverse transcriptase nucleoside analogues except for patients with subsequent genotypic resistance tests showing no resistance mutations to any of the study drugs. Previous exposure to inhibitors of HIV-1 integrase Previous major toxicity to any of the study drugs Spontaneous treatment interruptions in disagreement with the treating physician in the last year or loss to follow-up for at least 6 months, at least once in the last two years Current alcohol or drug abuse or any other condition which, in the judgment of the treating physician, may impair the patient's adherence to the new drug regimen and/or to the protocol's procedures Patients with grade 3 or 4 laboratory abnormalities at screening (except for lipid and glucose levels)

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: Tenofovir Emtricitabine Raltegravir<br>Patients switching to raltegravir with tenofovir+emtricitabine as backbone | Drug: tenofovir emtricitabine raltegravir<br>* switch from current antiretroviral regimen to raltegravir with tenofovir/emtricitabine as backbone<br>|
| Experimental: Lamivudine Abacavir Raltegravir<br>Switch from current antiretroviral regimen to raltegravir with abacavir/lamivudine as backbone | Drug: Lamivudine Abacavir Raltegravir<br>* Switch from current antiretroviral regimen to raltegravir with abacavir/lamivudine as backbone<br>|
| Experimental: Abacavir free<br>Patients switched to raltegravir whose backbone therapy should not be randomized in order to avoid the use of abacavir (HLA-B*5701 positive patients,Framingham score 20% or higher) | Drug: Abacavir free<br>* Patients will receive raltegravir with tenofovir/emtricitabine; data will be added to those of Tenofovir Emtricitabine Raltegravir arm in a separate longitudinal analysis comparing data at baseline and at 48 weeks. In this separate analysis, data will not be compared to those obtained from the Lamivudine Abacavir Raltegravir arm. The number of patients in this arm is not pre-established.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To verify the persistent control of the virus replication after the simplification to tenofovir+emtricitabine+raltegravir or to lamivudine+abacavir+raltegravir in patients with optimal virological suppression without any previous virological failure |  | 48 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to virological failure (two consecutive HIV-RNA levels > 50 copies/mL or a single value >1000 copies/mL) at survival analysis |  | 48 weeks | 
| Proportion of patients with viral load lower than 50 copies/mL at 48 weeks at the intention to treat analysis |  | 48 weeks | 
| Evolution of CD4 cell count during the 48 weeks of study |  | 48 weeks | 
| Evolution of adherence and quality of life during the 48 weeks of study |  | 48 weeks | 
| Evolution of raltegravir plasma concentrations during the 48 weeks of study |  | 48 weeks | 
| Evolution of metabolic parameters during the 48 weeks of study |  | 48 weeks | 
| Change of the results of neurocognitive tests at 48 weeks of study |  | 48 weeks | 
| Change of bone density and of adipose tissue by DEXA analysis at 48 weeks of study |  | 48 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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raltegravir switch toxicity, treatment experienced