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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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HIV Infections, HIV Lipodystrophy Syndrome

Intervention / Treatment
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* Drug: non-nucleoside reverse transcriptase inhibitors
* Drug: nucleoside reverse transcriptase inhibitors
* Drug: protease inhibitors


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: non-nucleoside reverse transcriptase inhibitors|nan|
|Drug: nucleoside reverse transcriptase inhibitors|nan|
|Drug: protease inhibitors|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | Measure Description | Time Frame |
| --- | --- | --- |
| 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 |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV infections, HIV Lipodystrophy Syndrome