Evaluation of Raltegravir Plus Maraviroc Therapy in Controlled HIV Patients Presenting With Lipohypertrophy (ROCnRAL)

Phase II Pilot Study Evaluating the Efficacy of Dual Therapy With Raltegravir Plus Maraviroc in Patients Receiving Suppressive Antiretroviral Therapy and Presenting With Lipohypertrophy (ANRS 157 ROCnRAL).

Evaluation of antiretroviral therapy combining Raltegravir and Maraviroc in patients with virological success, presenting with clinical lipohypertrophy.

Study Overview

• Status: Terminated
• Conditions: Human Immunodeficiency Virus; Lipohypertrophy
• Intervention / Treatment: Drug: Raltegravir-Maraviroc

Detailed Description

Assess the ability to maintain the plasma HIV viral load below the threshold needed for detection (< 50 copies/mL) at 24 weeks of raltegravir/maraviroc therapy without NRTIs and PIs, in patients with virological success and presenting with clinical lipohypertrophy.

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Paris, France, 75013
    • Hopital Pitie Salpetriere

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients infected with HIV-1 type B or CRF02.
• ≥ 18 years old
• Patients who have been receiving antiretroviral therapy for at least 5 years, and whose treatment has been stable for at least 6 months.
• Patients whose plasma viral load has been undetectable (below 200 copies/mL) over the last 24 months, and < 50 copies/mL for at least 12 months.
• Patients with an R5* tropic virus, as determined through DNA and with CD4 nadir ≥ 100/mm3
• Patients presenting with clinical lipohypertrophy recognized by themselves and by their doctors, and defined by increased volume of the abdominal and/or thoracic and/or cervical area (buffalo hump).
• Patients who have never been treated with raltegravir.
• Patients who have never been treated with maraviroc.
• Efficient contraception for women
• Free and informed written consent, signed by the patient and the investigator.
• Patients with health insurance. * To increase the certainty of selecting patients with an R5 virus, the HIV-1 tropism will be determined by the genotype method and interpreted with the Geno2pheno[coreceptor] algorithm and a false positive rate threshold for X4 virus at 20%, rather than the usual 10%.

Exclusion Criteria:

• X4, X4/5 or undetermined tropism of the HIV virus.
• HIV-2 or coinfection HIV-1/HIV-2.
• Chronic viral hepatitis B.
• Chronic viral hepatitis C requiring specific treatment over the first 24 weeks.
• Treatment with growth hormones.
• Hypolipemic or diabetes treatment, begun within the last 3 months.
• Pregnant or breastfeeding women.
• Haemoglobin < 7g/dl, neutrophils < 500/mm3, platelets < 50 000/mm3, creatinine clearance < 50 mL/min, alkaline phosphatases, ASAT, ALAT or bilirubin ≥ 3 times the upper limit of the normal range (N).
• Antiretroviral treatment associated to enzymatic inducer.
• Chronic alcohol consumption.
• Subjects under "sauvegarde de justice" (judicial protection due to temporarily and slightly diminished mental or physical faculties), or under legal guardianship.
• Subjects participating in another clinical trial evaluating different therapies and including an exclusion period that is still in force during the screening phase.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Raltegravir-Maraviroc; Raltegravir 400 mg twice a day + Maraviroc 300 mg twice a day	Drug: Raltegravir-Maraviroc; Raltegravir 400 mg twice a day + Maraviroc 300 mg twice a day; Other Names: Isentress and Celsentri

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Virological failure	Occurrence of virological failure, as verified by 2 consecutive plasma viral load measurements > 50 copies/mL, taken 2 to 4 weeks apart at most, during the first 24 weeks.	Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Viro-immunological efficacy	Proportion of patients with a HIV RNA viral load < 50 copies/mL.; Proportion of patients discontinuing the therapy:; Plasma genotypic resistance profile where the viral load is > 50 copies/mL.; Evaluation of DNA/RNA tropism in the event of failure.; Evaluation of plasma HIV RNA where the viral load is < 50 copies/mL, through ultrasensitive PCR testing.; Evolution of the CD4 and CD8 T-cell counts.; Blood concentration of raltegravir and maraviroc.	Between baseline and W48
Tolerability criteria and metabolic impact	Changes in glucose and lipid balance.; Changes in anthropometric measurements.; Number and severity of clinical and biological adverse effects.; Changes in bone mineral density and body composition, as measured by DEXA scan.; Changes in inflammation and endothelial activation markers between baseline and W48; Measurement of fat cells differentiation markers in adipose tissue biopsy samples	Between baseline and W48
Compliance	• Assessment of compliance conducted at screening and at W24 and 48.	Between baseline and W48
Quality of life	• Assessment of health-related quality of life conducted at baseline and at W24 and 48.	Between baseline and W48

Collaborators and Investigators

• Sponsor: ANRS, Emerging Infectious Diseases
• Collaborators: Merck Sharp & Dohme LLC; ViiV Healthcare
• Investigators: Principal Investigator: Christine Katlama, MD, Groupe Hospitalier Pitie-Salpetriere; Study Director: Dominique Costagliola, Inserm U943

Publications and helpful links

General Publications

• Soulie C, Assoumou L, Darty M, Rodriguez C, Donati F, Sayon S, Peytavin G, Valantin MA, Caby F, Schneider L, Canestri A, Costagliola D, Katlama C, Calvez V, Marcelin AG; ROCnRAL ANRS-157 Study Group. Virological factors associated with outcome of dual maraviroc/raltegravir therapy (ANRS-157 trial). J Antimicrob Chemother. 2015 Dec;70(12):3339-44. doi: 10.1093/jac/dkv280. Epub 2015 Sep 22.
• Katlama C, Assoumou L, Valantin MA, Soulie C, Duvivier C, Chablais L, Kolta S, Pialoux G, Mercie P, Simon A, Costagliola D, Peytavin G, Marcelin AG; ROCnRAL ANRS 157 Study Group. Maraviroc plus raltegravir failed to maintain virological suppression in HIV-infected patients with lipohypertrophy: results from the ROCnRAL ANRS 157 study. J Antimicrob Chemother. 2014 Jun;69(6):1648-52. doi: 10.1093/jac/dkt536. Epub 2014 Feb 16.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: December 1, 2011
• Primary Completion (Actual): April 1, 2013
• Study Completion (Actual): April 1, 2013

Study Registration Dates

• First Submitted: August 18, 2011
• First Submitted That Met QC Criteria: August 18, 2011
• First Posted (Estimate): August 19, 2011

Study Record Updates

• Last Update Posted (Estimate): July 24, 2015
• Last Update Submitted That Met QC Criteria: July 23, 2015
• Last Verified: July 1, 2015

More Information

Terms related to this study

• Keywords: HIV; Lipohypertrophy
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Slow Virus Diseases; HIV Infections; Acquired Immunodeficiency Syndrome; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; HIV Integrase Inhibitors; Integrase Inhibitors; HIV Fusion Inhibitors; Viral Fusion Protein Inhibitors; CCR5 Receptor Antagonists; Raltegravir Potassium; Maraviroc
• Other Study ID Numbers: 2011-002483-24