Anti-oxidants are substances intended to control a biological phenomenon called oxidative stress. Oxidative stress is a natural consequence of the use of nutrients by human cells, resulting in the production of highly reactive chemicals called free radicals. These can damage the components of cells, particularly their DNA, and also the cell membrane, disrupting its absorption of nutrients and other functions.

Most free radicals are mopped up by anti-oxidant substances like glutathione, vitamin E, vitamin C, beta carotene, superoxide dismutase (SOD) and various amino acids. However, some bodily processes, like fighting infection, produce far greater quantities of free radicals than the body's anti-oxidant stores can cope with. Polluted air, water and food, cigarette smoke, recreational and treatment drugs are also potent sources of free radicals.

Laboratory studies suggest that oxidative stress boosts HIV replication and in turn HIV replication boosts the production of free radicals, causing more oxidative stress. In particular, laboratory studies have shown that free radicals activate NF-kappaB, a cell protein which can trigger HIV to replicate where it has lain dormant in the cell's DNA. NF-kappaB production can be suppressed by some antioxidants. But when HIV genes become activated, levels of anti-oxidants in cells become drastically depleted as free radical production is stepped up.

Until now almost all research has concentrated on the relationship between oxidative stress and HIV, but HIV is not the only factor to influence free radical production in people at risk of developing AIDS. Increased activity by neutrophils white blood cells which fight bacterial and fungal infections boosts levels of free radicals, as does chronic inflammation of tissues. Oxidative stress itself contributes to inflammation at many sites in the body, which then starts another cycle of free radical release.

NF-kB also triggers cytomegalovirus (CMV) and Epstein-Barr virus (EBV) to reproduce, setting off another cycle of damage, since both viruses can trigger dormant HIV as well as causing oxidative stress and disease in their own right. Sexually transmitted infections, repeated antibiotic use, recreational drugs such as poppers and poor nutrition also increase the likelihood of high levels of free radical activity.

Free radicals have also been implicated in apoptosis or 'programmed cell death'. Apoptosis occurs when a T-cell takes the wrong cue from an antigen-presenting cell, which ought to alert T-cells to the presence of infections. When presented with an antigen in this way, a T-cell should take note of the antigen and become primed to proliferate and kill whenever it encounters that antigen in the future. Sometimes however, T-cells do not respond. They become anergic (literally meaning that they have no energy) and the next time they encounter the antigen which triggered their anergic state, they commit suicide. This is programmed cell death.

This process can be measured because it leaves cellular DNA chopped up in a very distinctive way. Researchers have noted that in people with HIV, a high level of apoptosis can occur which kills many T-cells even though they are never directly infected with HIV. The exact role of HIV in this process has still to be clarified. French researchers who have led the field in this area believe that free radicals play a key role in apoptosis.

One theoretical approach to treatment for people with HIV is to try to boost levels of anti-oxidants in the body. One important anti-oxidant is glutathione which is essential for the proper functioning of T-lymphocytes. It is thought to play an important role in cellular immune responses and prevent the activation of cells that are latently infected with HIV. Glutathione itself is very poorly absorbed as a supplement. Instead, many PWAs have used NAC, a cysteine precursor. The drug provides cysteine, which is converted into glutathione in the liver.

Viral load reduction with anti-oxidants

Other popular anti-oxidants include vitamin C (at high doses) and vitamin A. Because vitamin A is toxic at high doses it is usually taken in the form of beta-carotene which is safely broken down into vitamin A in the body. A small, placebo-controlled study has found a trend towards reduced HIV viral load among people taking vitamins E and C and researchers have suggested further research is warranted. For further information, see Vitamins and minerals in Anti-HIV therapy: Ways of attacking HIV.

Proponents of anti-oxidant use agree that anti-oxidants are likely to work most effectively when they are used in combinations. They also argue that anti-oxidants should be used in combination with treatments for specific conditions and with other agents which can support the immune system and reduce viral replication.