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.

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.

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