Document Type

Dissertation

Degree

Doctor of Philosophy (PhD)

Major/Program

Dietetics and Nutrition

First Advisor's Name

Adriana Campa

First Advisor's Committee Title

Committee chair

Second Advisor's Name

Marianna K. Baum

Second Advisor's Committee Title

Committee member

Third Advisor's Name

Fatma G. Huffman

Third Advisor's Committee Title

Committee member

Fourth Advisor's Name

Marcus S. Cooke

Fourth Advisor's Committee Title

Committee member

Fifth Advisor's Name

Florence Geroge

Fifth Advisor's Committee Title

Committee member

Keywords

HIV, oxidative stress, GSH, DNA damage

Date of Defense

3-18-2020

Abstract

HIV infection has been associated with glutathione (GSH) depletion, oxidatively damaged DNA, and inflammation. People living with HIV (PLWH) have subnormal levels of GSH and elevated levels of inflammation biomarkers such as C-Reactive Protein (CRP). Failure of the antioxidant enzymatic system increases oxidatively damaged DNA. The objective of this double-blinded randomized clinical trial was to supplement PLWH with a combination of N-acetylcysteine, a powerful antioxidant, and glycine, a precursor of GSH or placebo for three months to decrease oxidative stress and inflammation.

The trial recruited 30 PLWH from the Miami Adult Studies on HIV (MASH) cohort at the FIU Research clinic in the Borinquen Health Center, Miami-Dade, Florida. Participants were on stable ART, have undetectable HIV viral load, CD4 count ≥500 cells/µL, old, BMI ≤30 kg/m2, and free of co-morbid diseases. Cocaine was used by 50% of the participants and cocaine users were equally distributed between the intervention and placebo groups. We collected anthropometric measurements, pill count, CRP, demographics, and blood samples. The alkaline and enzyme modified comet assay was performed in whole blood to assess levels of oxidatively damaged DNA (SB/ALS, SB/ALS + oxidized purines, and oxidized purines only), and GSH was assessed using the Arbor Assay Glutathione Colorimetric. Supplementation significantly reduced levels of AS/ALS + oxidized purines (p=0.005)and SB/ALS (p=0.05). There was a direct correlation between BMI and SB/ALS (r= 0.585, p=0.009). Pill adherence was significantly associated with supplementation (β= -0.591, p=0.001), 75% in the intervention group were adherent. Oxidized glutathione (GSSG) decreased after supplementation, yet did not reach significance. Post-supplementation CRP significantly decreased among male gender (p=0.011), and was associated with decreased % body fat (p=0.022), BMI (p=0.004), and GSSG (p=0.019). Cocaine use was associated with lower CD4 cell counts (p=0.045) at baseline. Supplementing was effective in reducing levels of oxidatively damaged DNA and biomarkers of inflammation, and it also decreased body fat % and GSSG among PLWH from the MASH cohort.

Identifier

FIDC008940

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