Reconciling conflicting clinical studies of antioxidant supplementation as HIV therapy: a mathematical approach.
BACKGROUND
Small, highly reactive molecules called reactive oxygen species (ROS) play a crucial role in cell signalling and infection control. However, high levels of ROS can cause significant damage to cell structure and function. Studies have shown that infection with the human immunodeficiency virus (HIV) results in increased ROS concentrations, which can in turn lead to faster progression of HIV infection, and cause CD4+ T-cell apoptosis. To counteract these effects, clinical studies have explored the possibility of raising antioxidant levels, with mixed results.


METHODS
In this paper, a mathematical model is used to explore this potential therapy, both analytically and numerically. For the numerical work, we use clinical data from both HIV-negative and HIV-positive injection drug users (IDUs) to estimate model parameters; these groups have lower baseline concentrations of antioxidants than non-IDU controls.


RESULTS
Our model suggests that increases in CD4+ T cell concentrations can result from moderate levels of daily antioxidant supplementation, while excessive supplementation has the potential to cause periods of immunosuppression.


CONCLUSIONS
We discuss implications for HIV therapy in IDUs and other populations which may have low baseline concentrations of antioxidants.
van Gaalen
Rolina D
RD
Department of Applied Mathematics, University of Western Ontario, London, Ontario, Canada. rvangaalen@alumni.uwo.ca
Wahl
Lindi M
LM
D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D019587:Dietary Supplements; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D008297:Male; D008962:Models, Theoretical; D017382:Reactive Oxygen Species / Q000378:metabolism; D015819:Substance Abuse, Intravenous / Q000188:drug therapy*
D000975:Antioxidants; D017382:Reactive Oxygen Species