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Oxidative Stress in HIV-1-Infected Injection Drug Users


Alice M. Tang, Ph.D.
Johns Hopkins University, School of Hygiene and Public Health


Lecture Outline

  1. Rationale for research on the role of oxidative stress in HIV-1 infected injection drug users (IDUs).

  2. Review of oxidative stress.

  3. Review of studies linking oxidative stress and low-serum antioxidant levels in HIV infection.

  4. How do injection drug use and antiretroviral therapy complicate the issue?

  5. Areas for future research on the interactions between oxidative stress and antioxidants in the era of protease inhibitors.

Learning Objectives

Participants should be able to:

  • Understand the current knowledge on the role of oxidative stress and antioxidants in HIV infection.

  • Identify future research needs in the area of oxidative stress and antioxidants in injection drug users in the era of protease inhibitors.

Abstract

It has been hypothesized that the low-serum antioxidant levels observed in many HIV-infected populations is largely due to an increase in oxidative stress. Oxidative stress is defined as a disturbance in the equilibrium status of pro-oxidant/antioxidant systems of intact cells (1). In HIV infection, oxidative stress may be caused by both overproduction of reactive oxygen intermediates (ROIs) and a simultaneous deficiency of antioxidant defenses (2). Furthermore, injection drug use has been associated with increased levels of oxidative stress in animal models (3,4). Currently, there is widespread use of self-prescribed antioxidant supplementation among the HIV-infected population and a prevailing belief that high-dose supplementation is beneficial, or at the very least, not harmful. Data from our studies show that HIV-positive injection drug users (IDUs) who are on antiretroviral combination therapies including a protease inhibitor have significantly higher mean serum levels of several antioxidants, independent of dietary and supplemental intake, compared with both HIV-negatives and HIV-positives not taking protease inhibitors. This suggests that oxidative stress may be reduced in patients taking protease inhibitors. Based on our preliminary data, and preliminary data from other studies (5,6), it appears likely that the future of antioxidant supplementation therapy, if any, will be one in which different doses of supplements are recommended for HIV-infected patients on the various antiretroviral treatment regimens. More research is needed to determine the interactions among injection drug use, oxidative stress, antiretroviral therapy, and the use of antioxidant supplements in HIV infection. Until more known, caution should be exercised when using or recommending high-dose antioxidant supplementation in HIV-infected individuals, particularly in those on protease inhibitors, since moderate levels of oxidative stress are involved in a number of useful physiologic processes.

References

Thomas JA. Oxidative stress, oxidant defense, and dietary constituents. In: Shils ME, Olson JA, Shike M, eds. Modern nutrition in health and disease. Eighth ed. Philadelphia: Lea & Febiger, 1994, p. 501-512.

Greenspan HC and Aruoma OI. Oxidative stress and apoptosis in HIV infection: a role for plant-derived metabolites with synergistic antioxidant activity. Immunology Today 1994;15:209-213.

Devi BG and Chan AWK. Impairment of mitochondrial respiration and electron transport chain enzymes during cocaine-induced hepatic injury. Life Sci 1997;60:849-855.

Devi BG and Chan AWK. Cocaine-induced peroxidative stress in rat liver: antioxidant enzymes and mitochondria. J Pharm Exp Therap 1996;279:359-366.

Baruchel S and Wainberg MA. The role of oxidative stress in disease progression in individuals infected by the human immunodeficiency virus. J Leuk Biol 1992;52:111-114.

Repetto M, Reides C, Gomez Carretro ML, et al. Oxidative stress in blood of HIV infected patients. Clin Chim Acta 1996;255:107-117.

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