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

Study Description

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Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Human Immunodeficiency Virus; Lipohypertrophy	Drug: Raltegravir-Maraviroc	Phase 2

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 Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	48 participants
Allocation:	Randomized
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	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).
Study Start Date :	December 2011
Actual Primary Completion Date :	April 2013
Actual Study Completion Date :	April 2013

Arms and Interventions

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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 Name: Isentress and Celsentri

Outcome Measures

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Primary Outcome Measures :

1. Virological failure [ Time Frame: Week 24 ]
   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.

Secondary Outcome Measures :

1. Viro-immunological efficacy [ Time Frame: Between baseline and W48 ]
   • 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.
2. Tolerability criteria and metabolic impact [ Time Frame: Between baseline and W48 ]
   • 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
3. Compliance [ Time Frame: Between baseline and W48 ]
   • Assessment of compliance conducted at screening and at W24 and 48.
4. Quality of life [ Time Frame: Between baseline and W48 ]
   • Assessment of health-related quality of life conducted at baseline and at W24 and 48.

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

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Locations

France
Hôpital Pitié Salpétrière
Paris, France, 75013

Sponsors and Collaborators

French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)

Merck Sharp & Dohme Corp.

ViiV Healthcare

Investigators

Principal Investigator:	Christine Katlama, MD	Groupe hospitalier Pitié-Salpétrière
Study Director:	Dominique Costagliola	Inserm U943

More Information

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Additional Information:

Related Info 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Soulié 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, Soulié C, Duvivier C, Chablais L, Kolta S, Pialoux G, Mercié 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.

Responsible Party:	French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
ClinicalTrials.gov Identifier:	NCT01420523 History of Changes
Other Study ID Numbers:	2011-002483-24
First Posted:	August 19, 2011
Last Update Posted:	July 24, 2015
Last Verified:	July 2015

Keywords provided by French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS):

HIV; Lipohypertrophy

Additional relevant MeSH terms:

Acquired Immunodeficiency Syndrome; HIV Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Slow Virus Diseases	Raltegravir Potassium; Maraviroc; Anti-HIV Agents; Anti-Retroviral Agents; Antiviral Agents; Anti-Infective Agents; HIV Integrase Inhibitors; Integrase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; CCR5 Receptor Antagonists