Nucleoside analogues (nukes or NRTIs) such as AZT, d4T and ddI may be associated with a number of side effects, including the following:

• wasting of muscle tissue, including the heart
• malfunctioning kidneys
• swollen pancreas gland (pancreatitis)
• type 2 diabetes (non-insulin dependent)
• thyroid hormone abnormalities
• swollen livers due to excess fat deposits
• nerve damage (peripheral neuropathy)
• loss of fat just under the skin (subcutaneous fat)

Some researchers think that these problems occur because nukes damage the energy-producing parts of cells called "mitochondria" (Mt). Large numbers of damaged or malfunctioning Mt produce lactic acid (lactate). When high levels of lactic acid in the blood occur, this is known as "lactic acidosis." Generally, this condition is uncommon in PHAs. People with hepatitis B or C are at increased risk for developing lactic acidosis. Symptoms of lactic acidosis include the following:

• unexpected tiredness
• abdominal pain
• shortness of breath
• nausea and/or vomiting

The following blood tests help identify lactic acidosis:

• lactate levels of 5 mmol/L or greater
• bicarbonate levels of 20 mmol/L or lower

If left untreated, lactic acidosis can be deadly.

Doctors in Barcelona, Spain, have been studying remedies for lactic acidosis in PHAs.

Study details

The doctors enrolled 9 subjects (2 female, 7 males) for their study of this rare complication between March 2001 and July 2002. All subjects had symptoms of lactic acidosis as well as the following profile:

• average CD4+ count – 108 cells
• average viral load – 250,000 copies
• nukes used – AZT, ddI, d4T and 3TC
• 2 had cancers (lymphoma of the brain and kidney respectively)

Upon entry to the hospital, all subjects stopped using nukes and reduced their sugar intake. Water was given to them intravenously. They also received the following supplements:

• vitamin C – 1 gram every 12 hours
• L-carnitine – 1 gram every 12 hours
• vitamin B12 – 500 micrograms every 8 hours
• vitamin B1 – 250 mg every 8 hours
• vitamin B6 – 250 mg every 8 hours

Given this treatment, 8 of the 9 PHAs had their symptoms of lactic acidosis clear within a week. The ninth PHA's lymphoma in the kidney eventually resulted in death. Levels of lactate in the blood took more than a week to fall.

If this mix of B-vitamins and antioxidants is useful in the treatment of lactic acidosis, we wonder if smaller doses may also be helpful in preventing this complication. Researchers in Vancouver, British Columbia, are testing a combination of two B-vitamins in nuke users to find out if this strategy is effective.

REFERENCE

Bachs MR, Soler A, Villa C, et al. Focus on lactic acidosis therapy in HIV patients under nucleoside analogue reverse transcriptase inhibitors (NRTIs). Sixth International Congress on Drug Therapy in HIV Infection, 17-21 November 2002, Glasgow. Poster 125.

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