Evaluation of the Occurrence of Lipoatrophy in HIV-1 Infected Naive Patients

Randomized Comparative Study Evaluating the Rate of Occurrence of a Lipoatrophy Syndrome in ARVnaive HIV-1 Infected Patients Receiving NRTI-Sparing Antiretroviral Regimen (Hippocampe - ANRS 121)

The aim of this randomized study is to compare the occurrence of lipoatrophy in HIV-1 infected, naive patients receiving either a nucleoside reverse transcriptase inhibitor (NRTI)-sparing antiretroviral therapy with non-nucleoside reverse transcriptase inhibitor (NNRTI) and boosted protease inhibitor (PI), or a standard antiretroviral therapy with 2 NRTI plus either PI or NNRTI. Lipoatrophy is evaluated by measurement of fat volume by computed tomography (CT)-scan and DEXA (Dual Energy X-ray Absorptiometry).

Study Overview

• Status: Terminated
• Conditions: HIV Infections; HIV-Associated Lipodystrophy Syndrome
• Intervention / Treatment: Drug: non-nucleoside reverse transcriptase inhibitors; Drug: nucleoside reverse transcriptase inhibitors; Drug: protease inhibitor

Detailed Description

The study compare the rate of occurrence of lipoatrophy in ARVnaive HIV-1 infected patients receiving either a NRTI-sparing antiretroviral therapy with NRTI and boosted PI,or a standard antiretroviral therapy with 2 NRTI plus PI or NNRTI.

Patients were randomized (2:1:1) to either PI+NNRTI (Gp1) or standard therapy, 2NRTI+ either PI (Gp2) or + NNRTI (Gp3). The study-treatment were lopinavir/r 100/400mg bid or indinavir/r 100/400mg bid for PI-class, for NNRTI-class, efavirenz or nevirapine and all NRTIs except D4T and DDC at usual dosage.

Lipoatrophy is evaluated by evolution of subcutaneous fat in the limbs measured by DEXA (Dual Energy X-ray Absorptiometry)and CT-scan of the thighs between baseline and W96.

• Study Type: Interventional
• Enrollment: 112
• Phase: Phase 4

Contacts and Locations

Study Locations

• France
  • Paris, France, 75013
    • Service des Maladies infectieuses et Tropicales 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:

• Confirmed HIV-1-infected diagnosis
• Naive of antiretroviral treatment
• Plasma viral load (VL) over 5000 copies/ ml
• CD4 count below or equal to 350/mm3 or CD4 over 350/mm3 and VL over or equal to 100 000 copies/ml
• Written, informed consent after approval by the local human research ethics committee

Exclusion Criteria:

• Acute opportunistic infection
• Pregnancy or breast feeding
• Cytotoxic systemic chemotherapy except for Kaposi sarcoma
• Patient infected with B or C hepatitis requiring specific treatment at the beginning of the study
• Polynuclear neutrophils below 750/mm3
• Hemoglobin below 8 g/dl
• Platelets below 20 000/mm3
• Creatinine level over 1.5 (upper normal) UN
• ASAT, ALAT, bilirubin level over 3 UN

Study Plan

How is the study designed?

Design Details

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Evolution of subcutaneous fat in the limbs measured by DEXA and CT-scan of the thighs between baseline and Week 96

Secondary Outcome Measures

Outcome Measure
During the study until 96 weeks
Viro-immunologic efficacy: Proportion of patients with a plasma viral load below 400 and 50 copies/ml
Evolution of viral load
Evolution of CD4 lymphocytes
Evaluation of clinical safety
Evaluation of lipohypertrophic syndrome
Evaluation of glucidic and lipids metabolic profile
Evaluation of mitochondrial toxicity
Evaluation of bone toxicity by measurement of bone density
Evaluation of plasma trough concentration of protease inhibitors and non nucleoside reverse transcriptase inhibitors
Evaluation of intracellular concentration of nucleoside reverse transcriptase inhibitors
Evolution of quality of life using the World Health Organization Quality of Life in persons with HIV Brief Form (WHO-QOL-HIV BREF)

Collaborators and Investigators

• Sponsor: French National Agency for Research on AIDS and Viral Hepatitis
• Investigators: Study Chair: Dominique Costagliola, INSERM U 720; Principal Investigator: Claudine Duvivier, MD, Service des Maladies infectieuses et Tropicales, Hopital Pitie Salpetriere, Paris

Publications and helpful links

General Publications

• Soulie C, Assoumou L, Ghosn J, Duvivier C, Peytavin G, Ait-Arkoub Z, Molina JM, Costagliola D, Katlama C, Calvez V, Marcelin AG. Nucleoside reverse transcriptase inhibitor-sparing regimen (nonnucleoside reverse transcriptase inhibitor + protease inhibitor) was more likely associated with resistance comparing to nonnucleoside reverse transcriptase inhibitor or protease inhibitor + nucleoside reverse transcriptase inhibitor in the randomized ANRS 121 trial. AIDS. 2009 Jul 31;23(12):1605-8. doi: 10.1097/QAD.0b013e32832d9031.
• Duvivier C, Kolta S, Assoumou L, Ghosn J, Rozenberg S, Murphy RL, Katlama C, Costagliola D; ANRS 121 Hippocampe study group. Greater decrease in bone mineral density with protease inhibitor regimens compared with nonnucleoside reverse transcriptase inhibitor regimens in HIV-1 infected naive patients. AIDS. 2009 Apr 27;23(7):817-24. doi: 10.1097/QAD.0b013e328328f789.
• Duvivier C, Ghosn J, Assoumou L, Soulie C, Peytavin G, Calvez V, Genin MA, Molina JM, Bouchaud O, Katlama C, Costagliola D; ANRS 121 study group. Initial therapy with nucleoside reverse transcriptase inhibitor-containing regimens is more effective than with regimens that spare them with no difference in short-term fat distribution: Hippocampe-ANRS 121 Trial. J Antimicrob Chemother. 2008 Oct;62(4):797-808. doi: 10.1093/jac/dkn278. Epub 2008 Jul 18.

Study record dates

Study Major Dates

• Study Start: November 1, 2003
• Study Completion: July 1, 2005

Study Registration Dates

• First Submitted: July 21, 2005
• First Submitted That Met QC Criteria: July 21, 2005
• First Posted (Estimate): July 22, 2005

Study Record Updates

• Last Update Posted (Estimate): November 15, 2005
• Last Update Submitted That Met QC Criteria: November 14, 2005
• Last Verified: November 1, 2005

More Information

Terms related to this study

• Keywords: HIV infections; HIV Protease Inhibitors; HIV-Associated Lipodystrophy Syndrome
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Skin Diseases; 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; Disease; Lipid Metabolism Disorders; Skin Diseases, Metabolic; HIV Infections; Syndrome; Lipodystrophy; HIV-Associated Lipodystrophy Syndrome; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Viral Protease Inhibitors; Protease Inhibitors; Reverse Transcriptase Inhibitors; HIV Protease Inhibitors
• Other Study ID Numbers: ANRS121 HIPPOCAMPE