Clinical trial NCT01420523: Evaluation of Raltegravir Plus Maraviroc Therapy in Controlled HIV Patients Presenting With Lipohypertrophy
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 type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Human Immunodeficiency Virus
Lipohypertrophy
Keywords: HIV
Lipohypertrophy
Lead sponsor: ANRS, Emerging Infectious Diseases
Sponsor class: OTHER_GOV
Collaborators: name: Merck Sharp & Dohme LLC
name: ViiV Healthcare
First posted: 2011-08-19
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

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.

Eligibility 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.

Primary outcomes:
measure: Virological failure
timeFrame: Week 24
Secondary outcomes:
measure: Viro-immunological efficacy
timeFrame: Between baseline and W48
measure: Tolerability criteria and metabolic impact
timeFrame: Between baseline and W48
measure: Compliance
timeFrame: Between baseline and W48
measure: Quality of life
timeFrame: Between baseline and W48
Other outcomes:
Locations:
city: Paris
country: France
facility: Hôpital Pitié Salpétrière
Study officials:
affiliation: Groupe hospitalier Pitié-Salpétrière
name: Christine Katlama, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Inserm U943
name: Dominique Costagliola
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.