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.
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.
- Diagnosis of HIV lipoatrophy
- Receiving a stable stavudine- or zidovudine-containing ARV regimen
- HIV-1 RNA viral load less than 50 copies/ml
- Coagulopathies or other bleeding disorders
- Diabetes requiring medication
- Creatinine clearance less than 50 ml/min
- Pregnancy or breastfeeding