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

Phase 2

Terminated

• Conditions: Lipohypertrophy; Human Immunodeficiency Virus
• Interventions: Drug: Raltegravir-Maraviroc

• Registration Number: NCT01420523
• Lead Sponsor: ANRS, Emerging Infectious Diseases

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.

Study Timeline

• Study First Submitted: 2011-08-18
• Study First Submitted QC: 2011-08-18
• Study First Posted: 2011-08-19
• Study Start: 2011-12
• Primary Completion: 2013-04
• Study Completion: 2013-04
• Status Verified: 2015-07
• Last Update Submitted: 2015-07-23
• Last Update Posted: 2015-07-24

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 48

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Raltegravir-Maraviroc	Raltegravir-Maraviroc	Raltegravir 400 mg twice a day + Maraviroc 300 mg twice a day

Primary Outcome Measures

Name	Time	Method
Virological failure	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

Name	Time	Method
Viro-immunological efficacy	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.
Tolerability criteria and metabolic impact	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
Quality of life	Between baseline and W48	• Assessment of health-related quality of life conducted at baseline and at W24 and 48.
Compliance	Between baseline and W48	• Assessment of compliance conducted at screening and at W24 and 48.

Trial Locations

Locations (1)

Hôpital Pitié Salpétrière; 🇫🇷 Paris, France