Symptoms of high levels of lactic acid are a rare complication of treatment with nukes. To find out more about this complication, researchers in Western Australia studied several hundred people with HIV who used HAART for about 1½ years.
Researchers enrolled 349 HIV positive subjects (15% female, 85% male) whose average age was about 42 years. About 69% of subjects were taking HAART. Technicians took blood samples for analysis on a regular basis.
1.One subject developed a form of cancer called non-Hodgkin's lymphoma with tumours that had spread to his liver. He was not taking anti-HIV drugs.
2.Another subject developed a viral infection (CMV, or cytomegalovirus) of the brain and also heart damage. He was not taking anti-HIV therapy.
3.The third male was taking anti-HIV therapy and was known to abuse alcohol. His high lactate levels may have been due to alcohol abuse or use of nukes. After his last bout of heavy drinking, he did not take his medication as directed and his lactate levels fell within the normal range.
4.One subject developed nausea and abdominal discomfort six months after she started a regimen of d4T and nelfinavir (Viracept). Her lactic acid levels were high - 6.4 mmol/L at the time she was diagnosed with lactic acidosis. Just one month before this diagnosis her lactic acid levels were only slightly above normal readings.
5.This woman had been taking a combination of d4T, 3TC and nelfinavir for one year when she suddenly developed severe tiredness, vomiting, abdominal pain and a swollen liver. Her lactate level at this point was 8.2 mmol/L. A review of her test results suggested that her lactate levels were nearly normal just one month prior to the appearance of her symptoms.
During the study, another five subjects developed signs/symptoms (nausea, abdominal discomfort, abnormal liver enzyme levels, swollen liver) that suggested they had moderately high levels of lactic acid in the blood. Indeed, their lactic acid levels ranged between 2.8 to 4.1 mmol/L. Their doctors changed their treatment regimens by removing d4T (Zerit) and replacing it with either AZT or ABC (abacavir, Ziagen). As a result of this switch, their symptoms cleared.
According to their analysis, researchers found that the 140 subjects who were using d4T had, on average, significantly higher lactate levels than the 101 subjects who were using AZT-containing regimens.
On average, each subject in the study had his or her lactate levels measured about four times. Only five subjects had lactate levels that rose above the 5 mmol/L mark. Remember that the normal range for lactate in this study was 0.3 to 1.3 mmol/L. At some point in the study, the remaining subjects had lactate levels that were as follows:
Factors not significantly associated with higher-than-normal levels of lactate included:
One of the findings of this study is that regular measurement of lactate levels - taken every one to three months - was not useful in predicting which subjects would develop symptoms of lactic acidosis. This difficulty arises because lactic acid/lactate levels can often remain low or only mildly elevated until just before symptoms of lactic acidosis appear.
Another finding from this study is that many PHAs can tolerate mildly elevated lactate levels without developing symptoms of lactic acidosis. As well, in this study, only two subjects developed symptoms of severe lactic acidosis. If caught in the early stages, symptoms of mild lactic acidosis may clear up by replacing d4T with another nuke.
REFERENCES
1. John M, Moore CB, James IR, et al. Chronic hyperlactatemia in HIV-infected patients taking antiretroviral therapy. AIDS 2001;15(6):717-723.
2. Brinkman K. Management of hyperlactatemia: no need for routine lactate measurements. AIDS 2001;15(6):795-797.
3. Gaou I, Malliti M, Guimont M-C, et al. Effect of stavudine in mitochondrial genome and fatty acid oxidation in lean and obese mice. Journal of Pharmacology and Experimental Therapeutics 2001;297(2):516-523.
4. Moyle G. Toxicity of antiretroviral nucleoside and nucleotide analogues: is mitochondrial toxicity the only mechanism? Drug Safety 2000;23(6):467-481.
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Copyright © 2001 - TreatmentUpdate. Reproduced with permission. Reproduction of this article (other than one copy for personal reference) must be cleared through the Editor, The Canadian AIDS Treatment Information Exchange, 555 Richmond St. West, Suite 505, Box 1104, Toronto, ON, M5V 3B1 • Phone: 416-203-7122 • Toll Free: 1-800-263-1638 • Fax: 416-203-8284 http://www.catie.ca.
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