Clinical trial NCT00122655: Study Evaluating the Impact on Fat Distribution of Nucleoside Reverse Transcriptase Inhibitor (NRTI)-Sparing Regimens in Antiretroviral Experienced Patients With Lipoatrophy
Official title: A Randomized Prospective Study Evaluating the Impact on Fat Distribution of NRTI-Sparing Regimens in Antiretroviral Experienced Patients With Lipoatrophy ANRS 108 NONUKE Study
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: HIV Infections
HIV Lipodystrophy Syndrome
Keywords: HIV infections
HIV Lipodystrophy Syndrome
Lead sponsor: French National Agency for Research on AIDS and Viral Hepatitis
Sponsor class: OTHER_GOV
First posted: 2005-07-22
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
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 outcomes:
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
measure: Change in CD4 cell count between day 0 (D0) and week 48
measure: Change in lipid profile and glucidic metabolism between D0 and week 48
measure: Evolution of SAT/TAT and VAT/TAT between D0 and week 48
Other outcomes:
Locations:
city: Paris
country: France
facility: Service des Maladies infectieuses et Tropicales Hopital Pitie Salpetriere
Study officials:
affiliation: Service des Maladies Infectieuses Hopital Pitie-Salpetriere Paris
name: Marc Antoine Valantin, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: INSERM U720
name: Dominique Costagliola
role: STUDY_CHAIR
References: