Role of HIV on Glutathione Synthesis and Oxidative Stress



Status:Recruiting
Conditions:HIV / AIDS
Therapuetic Areas:Immunology / Infectious Diseases
Healthy:No
Age Range:Any
Updated:2/4/2013
Start Date:August 2010
Contact:R V Sekhar, MD
Email:rsekhar@bcm.edu
Phone:7137983908

Use our guide to learn which trials are right for you!


HIV infection is associated the development of HIV associated dyslipidemic lipodystrophy
(HADL) as a metabolic complication, and we have previously shown that these patients have
abnormal lipid kinetics. HIV patients with lipodystrophy have been reported to have
increased oxidative stress and deficiency of glutathione (GSH), the dominant endogenous
antioxidant protein, but the underlying mechanisms contributing to GSH deficiency are
hitherto unknown. Furthermore GSH metabolism has not been studied in HIV patients with
lipodystrophy, in whom the burden of risk factors promoting oxidative stress is highest.
Our previous studies in non-HIV human subjects with diabetes-related oxidative stress and
GSH deficiency have demonstrated that the latter is due to decreased synthesis of GSH.
Importantly, short-term dietary supplementation with the simple GSH precursor amino-acids
cysteine and glycine, boosted GSH synthesis and cellular concentrations, corrected GSH
deficiency, and reduced oxidative stress and oxidant damage. The current proposal will study
whether defective synthesis underlies GSH deficiency in patients with HIV lipodystrophy, and
will test a simple, inexpensive and rational therapy based on protein supplementation to
improve GSH synthesis and GSH concentrations in these patients. We will also measure plasma
oxidative stress, markers of oxidant damage and lipid kinetics in these subjects.


Inclusion Criteria:

1. HIV lipodystrophy (variable combination of peripheral fat loss or central obesity)

2. hypertriglyceridemia (fasting TG > 150)

Exclusion Criteria:

1. renal impairment (serum Creatinine above 1.5mg/dL), liver impairment (ALT and AST >
2x upper limit of normal)

2. any hormonal disorders such as hypothyroidism, hypercortisolemia, hypogonadism, or
diabetes mellitus on pharmacotherapy

3. evidence of infections other than HIV in the preceding 3 months

4. subjects with plasma triglyceride concentrations of ≥ 500mg/dL on triglyceride
lowering therapy

5. BMI < 20

6. established heart disease

7. Co-existing viral hepatitis B and C
We found this trial at
1
site
Houston, Texas 77009
?
mi
from
Houston, TX
Click here to add this to my saved trials