Study Evaluating the Impact on Fat Distribution of Nucleoside Reverse Transcriptase Inhibitor (NRTI)-Sparing Regimens in Antiretroviral Experienced Patients With Lipoatrophy

A Randomized Prospective Study Evaluating the Impact on Fat Distribution of NRTI-Sparing Regimens in Antiretroviral Experienced Patients With Lipoatrophy ANRS 108 NONUKE Study

The aim of this trial is to evaluate the impact on fat distribution of switching to NRTI-sparing regimens in lipoatrophic antiretroviral experienced patients with complete viral suppression.

Maintenance of virological suppression and immunological factors are also assessed.

Study Overview

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

Detailed Description

Limitations on achieving complete HIV eradication render it necessary to maintain highly active antiretroviral treatment over long periods, which may lead to the development of antiretroviral-associated toxicities. The current standard-of-care HAART regimens include a backbone of 2 nucleoside reverse transcriptase inhibitors (NRTIs). Many studies have demonstrated that NRTIs particularly thymidine analogue nucleosides are important contributors to the development of lipoatrophy. This antiretroviral family inhibits also the mitochondrial gamma-DNA polymerase, which leads to mitochondrial dysfunction and side effects such as peripheral neuropathy, pancreatitis and liver dysfunction.

• Study Type: Interventional
• Enrollment: 100
• 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:

• Males and non-pregnant females
• Confirmed laboratory diagnosis of HIV infection
• Patients receiving a 2 or 3 NRTI-containing antiretroviral treatment for at least 3 months
• Viral load below 400 copies/ml
• Patients with a clinical peripheral lipoatrophy isolated or associated with a lipohypertrophy self reported by the patient and confirmed by physical examination

Exclusion Criteria:

• Current antiretroviral therapy with 3 classes of antiretroviral therapy
• Previous virologic failure with a non-nucleoside reverse transcriptase inhibitor (NNRTI) or protease inhibitor (PI)
• Intolerance to nevirapine and efavirenz
• Acute opportunistic infection
• Diabetes
• Transaminase levels over 5 times above the upper normal limit
• Hepatitis B virus (HBV) co-infection if the patient is receiving lamivudine therapy
• Ongoing immunotherapy including interleukin-2 (IL-2) and interferon
• Pregnancy or planned pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Evolution from inclusion to week 48 of the peripheral fat tissue measured on computed tomography (CT) scan by a volumetric fat centralized evaluation of the thighs

Secondary Outcome Measures

Outcome Measure
Evolution of the viral load (VL) from inclusion to week 48 and proportion of patients with a VL over 400 copies/ml at week 48
Change in CD4 cell count between day 0 (D0) and week 48
Change in lipid profile and glucidic metabolism between D0 and week 48
Evolution of SAT/TAT and VAT/TAT between D0 and week 48

Collaborators and Investigators

• Sponsor: French National Agency for Research on AIDS and Viral Hepatitis
• Investigators: Principal Investigator: Marc Antoine Valantin, MD, Service des Maladies Infectieuses Hopital Pitie-Salpetriere Paris

Study record dates

Study Major Dates

• Study Start: January 1, 2001
• Study Completion: June 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 Lipodystrophy Syndrome
• Additional Relevant MeSH Terms: 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; Lipid Metabolism Disorders; Skin Diseases, Metabolic; HIV Infections; 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: ANRS108 NONUKE