Effectiveness of Nucleoside Supplementation or Switch to Tenofovir in Reversing Fat Loss in HIV Infected Adults

Phase 2

Completed

Conditions: HIV Infections
Lipodystrophy
Metabolic Diseases
Nutrition Disorders

Interventions: Drug: NucleomaxX
Drug: Tenofovir Disoproxil Fumarate

Registration Number: NCT00119379

Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Brief Summary: HIV lipoatrophy is a condition marked by fat loss; it occurs in many patients taking antiretroviral (ARV) therapy that includes nucleoside reverse transcriptase inhibitors (NRTIs). Lipoatrophy may be related to mitochondrial toxicity, a condition that can damage the heart, nerves, muscles, kidneys, and liver, and can affect the body's ability to produce energy. NucleomaxX is a food supplement consisting of a sugar cane extract high in nucleosides, which are building blocks that may counteract the negative effects of NRTIs. Tenofovir disoproxil fumarate (TDF) is an NRTI that may cause less lipoatrophy than other drugs in its class, such as zidovudine (ZDV) or stavudine (d4T). The purpose of this study is to determine whether nucleoside supplementation with NucleomaxX and substitution of TDF for ZDV or d4T in an ARV regimen can reverse fat loss caused by mitochondrial toxicity in HIV infected adults.

Study hypotheses: 1) The substitution of TDF for d4T or ZDV in patients with HIV lipoatrophy will result in an increase in mitochondrial DNA content in fat, skeletal muscle, and peripheral blood mononuclear cells (PBMCs), which in turn will lead to an improvement in mitochondrial function as assessed by electron transport chain (ETC) and oxidative phosphorylation pathway (OXPHOS) activity. The latter should lead to a decrease in fat apoptosis and in mitochondrial and lipid oxidative damage biomarkers. 2) Supplementation with uridine (via NucleomaxX) will increase mtDNA content in adipose tissue and increase body fat content.

Detailed Description: NRTIs are an important part of many ARV regimens used to treat HIV infected patients; however, the relationship between NRTI-induced mitochondrial dysfunction and lipoatrophy is still unclear and requires additional research. Additionally, the relationship between the gain in dual-energy x-ray absorptiometry (DEXA)-measured limb fat and mitochondrial DNA (mtDNA) content, mitochondrial function, fat apoptosis, and oxidative damage will also be examined in this study.

Patients will participate in this study for 48 weeks. Participants will be randomly assigned to one of two groups. Group 1 patients will receive NucleomaxX every other day. Group 2 patients will substitute TDF for ZDV or d4T every day in their current stable NRTI-containing ARV regimen. NucleomaxX will be provided to Group 1 patients, but TDF or any other ARV will not be provided by this study.

There will be 10 study visits, which will occur at study entry and Weeks 2, 4, 8, 12, 18, 24, 30, 36, and 48. Blood collection will occur at all visits. Additionally, urine collection, DEXA scans, and fat biopsies will be done at study entry and Weeks 24 and 48.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 50

Inclusion Criteria

Diagnosis of HIV lipoatrophy
Receiving a stable stavudine- or zidovudine-containing ARV regimen
HIV-1 RNA viral load less than 50 copies/ml

Exclusion Criteria

Coagulopathies or other bleeding disorders
Diabetes requiring medication
Creatinine clearance less than 50 ml/min
Pregnancy or breastfeeding

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
uridine supplementation	NucleomaxX	NucleomaxX 36 grams TID every other day
Switch to Tenofovir	Tenofovir Disoproxil Fumarate	Switch of AZT or d4T to Tenofovir Disoproxil Fumarate

Primary Outcome Measures

Name	Time	Method
Change in PBMC mtDNA	Baseline to Week 48	Peripheral blood mononuclear cell (PBMC) mitochondrial DNA (mtDNA), measured in copies/cell
Change in Fat mtDNA Content	Baseline to Week 48	Subcutaneous abdominal fat mitochondrial DNA (mtDNA)

Secondary Outcome Measures

Name	Time	Method
Change in Lumbar Spine Bone Mineral Density (BMD)	Baseline to Week 48	Change in lumbar spine bone mineral density (BMD) as measured by dual-energy x-ray absorbtiometry (DEXA) scan
Change in Trunk Fat	Baseline to Week 48	Change in trunk fat as measured by dual-energy x-ray absorbtiometry (DEXA) scan
Change in Hip Bone Mineral Density (BMD)	Baseline to Week 48	Change in hip bone mineral density (BMD) as measured by dual-energy x-ray absorbtiometry (DEXA) scan
Change in Limb Fat	Baseline to Week 48	Change in limb fat as measured by dual-energy x-ray absorbtiometry (DEXA) scan