The Role of Oxidative Stress in HIV Open Access

Cribbs, Sushma K (2013)

Permanent URL: https://etd.library.emory.edu/concern/etds/g445cd57c?locale=en
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Abstract

Abstract

The Role of Oxidative Stress in HIV

By Sushma K. Cribbs, M.D.

Objective: Despite the advent of anti-retroviral therapy (ART), lung infections continue to be a leading cause of death in HIV-infected individuals. There is substantial evidence that HIV infection causes oxidative stress, both in pre-clinical and clinical studies. Oxidative stress can be generated through several mechanisms including the oxidation of extracellular thiol disulfide pairs such as glutathione/glutathione disulfide (GSH/GSSG) and cysteine/cystine (Cys/CySS). Measuring redox in HIV-infected individuals may identify those with chronic oxidative stress who are at increased risk for lung infection. Therefore, we sought to estimate the association between HIV infection and oxidative stress in the lung, as reflected by decreased levels of GSH and Cys in the epithelial lining fluid.

Study design: Cross-sectional study of subjects with and without HIV.

Methods: Subjects with and without HIV infection were enrolled at Grady Memorial Hospital, Atlanta GA. Individuals were excluded if they had evidence of major medical co-morbidities, were malnourished or smoked cigarettes. Exhaled breath condensate (EBC) and bronchoscopy with bronchoalveolar lavage (BAL) were performed to assess for airway oxidant stress. Primary outcomes were GSH and Cys levels in the BAL.

Results: 26 HIV and 28 non-HIV subjects were enrolled. There were no significant differences in median BAL fluid GSH and Cys levels between HIV and non-HIV-infected subjects.HIV infection without ART was associated with an estimated OR of 2.12 for low BAL GSH. Although not statistically significant, there was a trend showing that HIV infection with ART was associated with increased BAL GSH. There was no association observed between BAL Cys, HIV infection, age, BMI and use of ART.

Conclusion: HIV infection without ART was associated with increased oxidative stress in the lung, as measured by BAL GSH. There was a trend showing that HIV infection with ART was associated with decreased oxidative stress, suggesting that the use of ART is protective. Further study needs to be done to address the role of antioxidants, particularly GSH supplementation, to mitigate HIV-induced oxidative stress and enhance lung health in HIV-infected individuals.

Table of Contents

Table of Contents
A. Introduction...1
B. Background...3
C. Methods...6
D. Results...10
E. Discussion/Conclusion...13
F. References...17
G. Tables/Graphs/Charts...21

Table 1. Demographic characteristics of HIV-infected Subjects and Non-HIV-infected Subjects Enrolled in the Study...21
Figure 1a. Box plots of GSH levels in BAL fluid of patients with and without HIV...22
Figure 1b. Box plots of GSH levels in EBC of patients with and without HIV...22
Figure 2a. Box plots of Cys levels in BAL fluid of patients with and without HIV...23
Figure 2b. Box plots of Cys levels in EBC of patients with and without HIV...23
Table 2. Multiple Linear Regression Model for Log-transformed BAL GSH Levels...24
Table 3. Multiple Linear Regression Model for Log-transformed BAL Cys Levels...25
Figure 3. Scatter Plot of Log-transformed GSH and Cys levels in EBC versus BAL...26
Figure 4a. Box plots of GSH levels in BAL fluid and EBC of patients with HIV...27
Figure 4b. Box plots of GSH levels in BAL fluid and EBC of patients without HIV...27
Figure 5a. Box plots of CYS levels in BAL fluid and EBC of patients with HIV...28
Figure 5b. Box plots of CYS levels in BAL fluid and EBC of patients without HIV...28

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