Levels of lactic acid are normally carefully regulated by the liver. Small increases in lactic acid (called hyperlactataemia) are relatively frequent, especially after exercise, usually returning to normal spontaneously.

If they reach a higher level, there is a risk of lactic acidosis which is a more rare but potentially fatal side effect related to nucleoside analogues (AZT, 3TC, d4T, ddI and abacavir).

Not only do these drugs form the background treatments for nearly all HIV combinations, but the symptoms of lactic acidosis are common side effects of other drugs and indeed symptoms common anyway.

Symptoms include:

Before combination therapy was available, this was only very rarely seen in HIV, and may well have been under diagnosed. Recently the number of reports of lactic acidosis have increased and drug packaging now includes a clearer caution about this risk.

Pregnancy may be an additional risk factor for lactic acidosis when using nucleosides.

Lactic acidosis is diagnosed through examination, lab tests, an abdominal CT scan or liver biopsy. Although this toxicity is believed to be a result of damage to part of the cell called the mitochondria, there is no simple test for determining people at highest risk.

Although lactic acid in blood can be measured, it is not clear whether high levels increase the risk of lactic acidosis. Over 50% of people showing a high reading on one result, return to normal with the confirmatory test. There appears to be no pattern between high levels and risk of severe toxicity.

Because lactic acid increases even with any physical activity, confirmatory tests should always be taken after you have completely rested for at least 20 minutes. Even going to the gym the day before may affect the results.

Early diagnosis is essential and contacting your doctor if you have any of the symptoms is important.

High doses of vitamin B complex with L-carnitine (both IV) until lactate levels normalise was reported in a Dutch study to improve the chances of survival.

The use of oral antioxidant supplements such as vitamin C, vitamin B complex, L-carnitine or co-enzyme-Q may help.

There are no clear guidelines for restarting nucleoside therapy after a serious case of mitochondrial toxicity. Although caution is warranted, lack of other antiretroviral options has lead to people restarting without further toxicity.

This proposed mechanism of mitochondrial toxicity is thought to be responsible for other serious side effects..

Pancreatitis is an inflammation of the pancreas characterised by abdominal or back pain and vomiting. It can also be alcohol induced and there is little specific treatment. Blood tests are usually checked to confirm a diagnosis of pancreatitis. Pancreatitis can be fatal if not treated early, and can be prevented by stopping or changing HIV drugs.

Hepatic steatosis or ‘fatty liver’ can develop from alcohol use, hepatitis, obesity and drug toxicity with nucleosides.

This build-up of fat in the liver can affect the way it processes fats. Hepatic steatosis often also leads to lactic acidosis, described above. People who weigh over 70kgs, especially women, may be more at risk of developing hepatic steatosis and lactic acidosis.

Steatosis is also common in HIV-infected children. Ultrasonography is a sensitive, accurate, non-invasive screening tool to detect steotosis as this is not always shown in liver function tests.