Prospective Evaluation of Etravirine for HIV-infected Patients in Need of Lipid-lowering Drugs

Study Overview
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Brief Summary
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Dyslipidaemia, characterized by raised triglyceride and low-density lipoprotein (LDL) cholesterol and reduced high-density lipoprotein (HDL) cholesterol levels, is common in HIV-infected individuals, and has been associated with HIV infection itself and antiretroviral therapy (ART). These abnormalities are well-established markers of cardiovascular (CVD) risk in the general population. Studies have suggested an increased risk of CVD associated with ART exposure over and above that conveyed by traditional cardiovascular risk factors. In HIV population to reduce lipid parameters, the most usual clinical strategy remains to add a statin treatment. Recent studies suggested ART switch can represent an interesting alternative to statins to reduce lipid plasma levels. The purpose of this study is to evaluate the frequency with which the replacement of LPV/r (lopinavir/ritonavir), ATZ/r (atazanavir/ritonavir), DRV/r (darunavir/ritonavir) or EFV (efavirenz) by ETR (Etravirin) in dyslipidemic patients with suppressed viremia would obviate the necessity to administer statins. A prospective, phase III study in which the statin treatment of dyslipidemic HIV patients on antiretroviral drugs (ARVs) will be interrupted during 4 weeks is proposed. At week 4, patients qualifying for a lipid lowering drug (calculated LDL-C≥ 3mmol/L) will replace EFV, LPV/r, DRV/r or ATZ/r by ETR. The proportion of patients not qualifying anymore for a statin treatment at 12 weeks (i.e. after 8 weeks of ETR treatment) will be determined. Additionally, the lipid level changes will be assessed at 12 weeks. Inflammatory markers will be measured at baseline, at drug switch and at the end of the study Study drug will be provided by the drug manufacturer (Janssen-Cilag, AG). Compliance for study drug will be done at week-4 and week-12, Returned study medication will be counted and the amount notified on the Case Report Form (CRF).

Official Title
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Phase III Prospective Multicentric Trial Evaluating Etravirine for HIV Infected Patients in Need of Lipid Lowering Drugs: the ETRALL Trial

Conditions
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HIV Infection

Intervention / Treatment
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* Drug: stop statin and switch to an antiretroviral drug with less impact on lipid metabolism


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: On statin treatment for at least 3 months (fluvastatin, simvastatin, pravastatin, rosuvastatin, or atorvastatin) for primary prevention of cardiovascular disease HIV Ribonucleic Acid (RNA) below 50 copies/mL, minimum duration 3 months On a stable (> 3 months) ARV treatment including at least one of the following drugs: LPV/r, ATZ/r, DRV/r, or EFV No previous virological escape or virological escape documented with a genotype at the time of failure only showing a K103M mutation. Exclusion Criteria: Probability of cardiovascular complications of > 20% according to the Swiss GSLA (Groupe de travail Lipide et Athérosclérose/Swiss Atherosclerosis Association) guidelines Previous cardiovascular disease (including stroke) Known diabetes Known intolerance of ETR Presence of a documented drug mutation (excluding the K103M) Regimen including non-boosted ATZ Known hyperlipidemia before ARV initiation

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Etravirine switch<br>Patients in need of lipid-lowering drug switched from boosted PI or EFV to Etravirine | Drug: stop statin and switch to an antiretroviral drug with less impact on lipid metabolism<br>* Switch from a boosted PI or efavirenz based ART regimen to etravirine 400 mg/day once daily for patients in need of lipid lowering drugs (statin) after one month wash out of statin<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients not qualifying anymore for statin treatment |  | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| fasting lipids changes |  | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV infection, lipid lowering drugs, etravirine, patient, statin treatment, EFV or boosted PI antiretroviral treatment