Should You Test Your Lactate Levels??

Most researchers do not feel testing lactate is appropriate except in pregnancy, or if a patient has symptoms. Kees Brinkman reported at Retrovirus that his testing for this study was not reliable and results were inconsistent. Here are several reasons researchers suggest for not testing lactate. If you test lactate and levels are moderately elevated, they may be normal next time you test. If they are moderately elevated, that does not necessarily mean this will lead to highly elevated levels. So if you learn you have moderately elevated levels, what would you do with it? And, what does it mean? Researchers are unsure what moderately elevated levels mean, or if anything should be done if they are moderately elevated.

Another potential utility for lactate levels was suggested by Brew and colleagues in Abstract 9 presented at Retrovirus. He found that patients with neuropathy on d4T had elevated lactate. He suggested that if you find elevated lactate for a person on d4T with neuropathy, you can conclude that the neuropathy is drug related and by changing the d4T the lactate will normalize & neuropathy should dissipate. 

Hyperlactatemia in HIV-Infected Patients: The Role of NRTI Treatment
     S. M. E. Vrouenraets, M. Treskes, R. M. Regez, N. Troost, H. M. Weigel, P. H. J. Frissen, and K. Brinkman, Onze Lieve Vrouwe Gasthuis, Amsterdam, The Netherlands.

Background:
Long-term treatment with NRTIs can induce mitochondrial dysfunction, most severely represented by lactic acidosis. Diagnostic tests for mitochondrial dysfunction are lacking, and it is unclear whether lactic acidosis is preceded by a period of (asymptomatic) hyperlactatemia. The objectives of this study were to determine the occurrence of hyperlactatemia in HIV-infected patients on NRTI treatment and to evaluate the possible risk factors.

Methods:
Cross-sectional analysis of lactic-acid levels in asymptomatic HIV-infected patients. Hyperlactactemia was considered mild if between 2.1-5 mmol/l and serious if >5 mmol/l, and lactic acidosis was defined as lactic acid >5 mmol/l and bicarbonate <20 mmol/l. Possible risk factors, such as current and preceding NRTI treatment as well as concurrent liver disease, were analyzed.

Results:
223 asymptomatic HIV-infected patients were studied, including 173 patients (78%) on NRTI treatment. Lactic-acid level was normal in 135 (78%) on NRTI treatment and in 46 (92%) without treatment. Mild hyperlactatemia was found in 37/173 (21%) treated and 4/50 (8%) untreated patients (c2p < 0.05). One treated patient had serious hyperlactatemia without acidosis but retested normal 2 weeks later. In multivariate analysis, an increased risk was found for treatment combinations containing d4T (OR 10.0; 2.5-39.6), AZT (OR 6.8; 1.6-28.4) and/or abacavir (OR 6.7; 1.5-30.5), but not for DDI-, 3TC- or DDC-containing treatment regimens. There was no statistical association between lactic-acid level and positive hepatitis serology or elevated liver enzymes (ALT). Longitudinal observation showed wide inter- and intra-individual fluctuations, while elevated lactate levels were not consistent in the same individuals.

Conclusions:
Although there was a clear correlation between hyperlactatemia and NRTI treatment, the value of lactate measurement for individual treatment monitoring remains obscure.

Low, asymptomatic lactatemia (2-5 mmol/L) does not appear to predict the development of more severe lactatemia.

Mitochrondrial toxicity and lactic acidemia
Andrew Carr gave a state of the art lecture on mitochondrial toxicity. Nucleoside analogue reverse transcriptase inhibitors are thought to inhibit the mitochondrial polymerase G, resulting in mitochondrial toxicity. Elevated lactate levels (lactic acidemia) may be one of the consequences of mitochondrial toxicity. He proposed the following classification of lactic acidemia: normal <2, mild 2-5, moderate 5-10 and severe >10 mmol/L. Testing lactate should be considered in women who are pregnant and who have symtoms, such as those listed below. A recent safety alert from the US Food and Drug Administration and Bristol-Myers Squibb described lactic academia and deaths in 3 pregnant women receiving antiretroviral therapy that included stavudine and didanosine. Subjects with mild lactic acidemia may be asymptomatic, whereas patients with moderate lactic acidemia may show symptoms such as fatigue, malaise, gastrointestinal symptoms and nausea, The severe form of lactic acidemia is often acidotic which is associated with a high mortality. With regard to these serious consequences NRTI should be discontinued when lactate levels increase above 5-10 mmol/L. He did not recommend routine testing of lactate levels, but clinicians should be alerted by symptoms associated with this syndrome. If a patient is tested & has ild or moderate increases lactate should be retested. As Brinkman reported above testing results can be variable. Performing proper testing procedures such as drawing blood samples, handling of samples, shipping & lab evaluation can be tricky and there are differences of opinion about how to perform these procedures.

Lonergan and colleagues found that the incidence of lactic acidemia was more than ten times higher for any d4T-containing regimen compared with a regimen without d4T. The greatest risk occurred when ddI or ddI/3TC was combined with d4T. However, patients with lactic acidemia could be safely rechallenged with other NRTIs such as abacavir or ZDV or both.

Vrouenraets and colleagues found a prevalence of elevated lactate levels in 22% of 223 patients on NRTIs. Consistent with the previous study, they found an increased risk for d4T containing regimens, but also for AZT and abacavir.