Bear in mind this study is small. Conclusions about lactate measurements and its role in clinical practice are not yet resolved. The Britsh Columbia Center where Marianne Harris conducted this study is as best we know likely one of few that systematically looked at lactate. Further studies are needed and likely to follow

Marianne Harris, from the British Columbia Centre for Excellence in HIV/AIDS Clinic in Vancouver, reported on her study exploring the utility of using an ordinary blood test to measure lactate levels and look for toxicity. The blood samples were processed by an ordinary commercial lab. Because of the recently emerging concerns about lactic acidosis resulting from HIV NRTI therapy, and because a number of researchers believe ordinary lab testing for lactate does not produce reliable results, Harris conducted this study to see if there is a reliable way to monitor patients. Some leading researchers have said lactate testing must be performed properly and testing in ordinary labs may not be reliable. Generally they feel that lactate testing if done without special methodologies will not be reliable. In this study, Harris used a commercial ordinary lab in her hospital. This is just an initial study and more studies may be required to look at using regular labs. In addition it appears to me as though she saw variability in lactate test values suggesting that, like sometimes other lab tests, a single lab test value can be inaccurateFor this study, Harris performed random venous (blood draws) lactic acid levels (RVLA) to test for the consistency, frequency and predictability and predisposing factors for abnormal RVLA.

Data were analyzed for all HIV+ patients in the British Columbia Drug Treatment Program who had RVLA measured between August 3 1999 and January 21 2000. To check the consistency of testing lactate levels for individuals, two RVLA values were compared for all patients having „ 2 mmol/l among 149 patients on stable medication. Harris found a positive linear relationship between the first and the second lactic acid measurement taken from the same person. The correlation coefficient is 0.7 and that's statistically siginificantly different than 0 (p<0.001).

Regarding the frequency of abnormal values, the upper limit of normal in Harris' lab was 2.1 mmol/l. Frequency was based on each patient's first RVLA level and on 331 individual patient's values. RVLA levels were >2.1 mmol/l in 68 of 331 patients (20.5%), and >3.0 mmol/l in 27 of 331 patients (8.1%). RVLA levels were consistently (both tests) normal in 105 patients (£ (2.1 mmol/l), and consistently abnormal (>2.1 mmol/l) in 33 patients.

Harris conducted an analysis of factors that may or may not correlate to RVLA levels. The following factors were NOT correlated with abnormal RVLA levels: gender; age; CD4 count; time on antiretroviral therapy (ART); time on NRTI, PI, and NNRTI therapy; current AZT, abacavir or NNRTI therapy; time on AZT, abacavir, and NNRTI therapy.

Harris reported the following factors were significantly associated with abnormal RVLA levels (univariate analysis): current d4T (p<0.001); longer time on d4T (p=0.001); current hydroxyurea (p=0.001); current ddI (p<0.001); current 3TC (0.028); current PI (0.009); currently taking more NRTIs (<0.001); currently taking more ARTs (0.001); lower plasma viral load (0.001).

Muktivariate analysis indicated that abnormal RVLA levels were independently associated with current d4T (odds ratio 4.1, p=0.004), time on d4T (odds ratio 1.1 per 3 months, p=0.036), current treatment with hydroxyurea (odds ratio 4.1, p=0.005).

Harris concluded that RVLA levels were consistent and frequently above the normal range. As you may know many of the lipodystrophy studies reported on at various AIDS conferences suffer from poorly designed studies, and therefore it is difficult to interpret and rely on the results. I'm not convinced this study does not suffer from some of the same problems. For example, what if some individuals in this study had previous use of AZT and some didn't, Harris didn't comment on this. What if some individuals had longer exposure previously to AZT than other patients? This might affect the results of the study.

Background: Persistent elevations in random venous lactic acid (RVLA) levels may be seen in patients receiving NRTIs. It is not known whether these lab abnormalities correlate with any demonstrable physiological dysfunction.

Objective: To characterize the aneorobic threshold (AT) among patients on antiretroviral therapy with and without elevated RVLA levels

(The study in abstract 34 reports on the frequency and consistency of abnormal lactate lab values, but this study was conducted to see if the elevated RVLA lab values actually translate into a real affect, in this case on exercising.)

Methods: All patients seen in a tertiary care HIV clinic who had persistently elevated RVLA („ 2 consecutive readings >2.1 mmol/l) while receiving antiretroviral therapy and a group of matched controls with normal RVLA were requested to undergo cardiopulmonary exercise testing. AT from respiratory gas measurements was expressed as a percentage of predicted maximal oxygen consumption. To differentiate reduced AT due to mitochondrial activity from reduced AT due to poor cardiovascular fitness, a pattern of mitochondrial dysfunction was defined a priori to be a combination of reduced AT (<40%), decreased oxygen uptake (<60% predicted) and increased minute ventilation (>80 l/min).

Results: Twenty-two patients have performed the exercise test thus far, 17 with high RVLA (mean 3.4, range 2.2-6.8 mmol/l). and 5 controls. In the high-RVLA group, 11/17 had reduced AT and 7/17 had the pattern of mitochondrial dysfunction. In contrast, 2/5 controls had reduced AT but 0/5 had the pattern of mitochondrial dysfunction.

Conclusion: Cardiopulmonary exercise testing showed decreased AT with a pattern of mitochondrial dysfunction in 7/17 patients with abnormal RVLA levels, compared to 0/5 patients on antiretroviral therapy with normal RVLA levels. These preliminary results indicate that chronic, low-level increases in RVLA may indeed be indicative of impairments in oxidative metabolism.

DRAWING BLOOD SAMPLE FOR TESTING LACTATE-
The most critical thing in the immediate period at the time of the blood draw is forearm exercise, so the patients are asked not to pump their fist when the blood is drawn. The samples are drawn in fluoride/oxalate tubes and are stable for up to 7.5 hours at room temperature (though in reality they are probably processed within an hour or 2, at most). They are drawn and processed right here in our hospital lab, so shipping isn't an issue, anyway. Kees Brinkman uses the same procedure, and confirmed that the samples are stable for several hours at room temp.