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

Phase 3

Completed

• Conditions: HIV Infection
• Interventions: Drug: stop statin and switch to an antiretroviral drug with less impact on lipid metabolism

• Registration Number: NCT01543035
• Lead Sponsor: Calmy Alexandra

Brief Summary

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).

Detailed Description

Not available

Study Timeline

• Study Start: 2011-12
• Study First Submitted: 2012-02-27
• Study First Submitted QC: 2012-03-01
• Study First Posted: 2012-03-02
• Primary Completion: 2013-07
• Study Completion: 2013-08
• Status Verified: 2013-12
• Last Update Submitted: 2013-12-11
• Last Update Posted: 2013-12-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 34

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Etravirine switch	stop statin and switch to an antiretroviral drug with less impact on lipid metabolism	Patients in need of lipid-lowering drug switched from boosted PI or EFV to Etravirine

Primary Outcome Measures

Name	Time	Method
Proportion of patients not qualifying anymore for statin treatment	12 weeks

Secondary Outcome Measures

Name	Time	Method
fasting lipids changes	12 weeks

Trial Locations

Locations (7)

Universitätsspital Basel Klinik für Infektiologie & Spitalhygiene; 🇨🇭 Bale, Switzerland

Inselspital PKT2B / Poliklinik für Infektiologie; 🇨🇭 Berne, Switzerland

Hôpital Neuchâtelois - La Chaux-de-Fonds Service des Maladies infectieuses; 🇨🇭 La Chaux-de-Fonds, Switzerland

HUG /Division des Maladies infectieuses Unité VIH/SIDA; 🇨🇭 Geneva, Switzerland

CHUV / Service des maladies infectieuses Médecine 2; 🇨🇭 Lausanne, Switzerland

Universitätsspital Zürich Division of Infectious Diseases and Hospital Epidemiology Department of Internal Medicine; 🇨🇭 Zurich, Switzerland

Kantonsspital / Infektiologie und Spitalhygiene Departement Innere Medizin; 🇨🇭 St Gallen, Switzerland