• Mitochondrial function and exercise capacity in HIV-infected patients with lipodystrophy (Poster, TuPpB1232)
  Authored by B.T. Roge, J. Calbet, K. Muller, H. Ullum, H.W. Hendel, J. Gerstoft, B.K. Pedersen, B. Saltin

• Screening for nucleoside-associated lactic acidosis (Poster, TuPpB1233)
  Authored by M. Harris, A. Tesiorowski, J.S.G. Montaner

• The occurrence of hyperlactatemia in HIV-infected patients on NRTI treatment (Poster, TuPpB1234)
  Authored by S. Vrouenraets, M. Treskes, R.M. Regez, N. Troost, H.M. Weigel, P.H.J. Frissen, K. Brinkman

Mitochondrial function and exercise capacity in HIV-infected patients with lipodystrophy (TuPpB1232)

There has been an increased amount of attention to the possibility that nucleoside antivirals have a side effect that alters the function of mitochondria. Mitochondria are in virtually all of the body's cells and are responsible for the fuel and energy of cell function. If the mitochondria are impaired by nucleoside antivirals, then we might expect to see reduced exercise capacity in someone, as the muscle cells might have less energy to do the exercise. With this as a rationale, the researchers did a small study with eight people who were on combination antivirals. The patients were required to exercise regularly and were compared with six others who were HIV-negative and similar in age, gender, and height. They focused on measuring blood lactate, which is produced when mitochondria are not functioning optimally in cells. They reported seeing some differences in those who were HIV-positive, as there was more lactic acid production while exercising. However, at "peak" exercise levels, these differences were no longer seen.

It is unclear what these results mean at this point. Since the differences were not true at all levels of exercise it may reflect some vulnerability in those who are positive on medications, but this difference was subtle. In addition, as they did not have any participants who were HIV-positive and not on medication, we cannot say from this study how much the outcome was due to being on medications vs. just having HIV infection. Nonetheless, there will be more exploration of the impact of nucleoside antivirals on mitochondrial function.

Screening for nucleoside-associated lactic acidosis (TuPpB1233) and
The occurrence of hyperlactatemia in HIV-infected patients on NRTI treatment (TuPpB1234)

Screening for lactic acidosis for those on nucleoside RT antivirals has become more discussed in recent months with the hope that this lab finding may explain some of the side effects seen in those on antivirals. These two studies explored the possible role of using lactic acid measurements as a way to identify those who might be at risk for medical problems, allowing us to intervene before symptoms might occur.

In the first study (TuPpB1233), researchers explored taking random lactic acid measurements in 70 people who were on antiviral medications, including nucleoside antivirals. Using an upper limit of 2.1 as the normal in their lab, they noted that 36% of these people had an elevated level, but only 13% had a measurement of 3.0. However, all of those with elevated levels felt well with no symptoms, suggesting a problem. They further looked at four people who had both a lactic acid level above three and an anion gap over 12 which is another measurement of acid levels in the blood. Of these four, three people felt well, while one person did have symptoms consistent with what researchers think occurs with elevated lactic acid levels (i.e., fatigue and weight loss).

In the second study (TuPpB1234), the researchers measured random lactic acid levels in those who were feeling well. Measurements were done in 138 participants, of whom 75% were on nucleoside antivirals. Most had normal screening levels, while between 20-25% had slightly elevated levels, and the levels were higher than those not on antivirals. Of those who did have a mild elevation, there was no statistically significant difference in the rates of those on AZT versus d4T nor was there a correlation between the duration of nucleoside RTI treatment and lactate levels. They found one person who did have a high lactic acid level, but this returned to normal without changing the antivirals two weeks later.

Since there was virtually no one who had symptoms consistent with elevated lactic acid levels, this study suggests that at least a small increase in lactic acid can be measured in perhaps a third of people on antivirals without clear clinical significance. Therefore it does not at this point make sense to use lactic acid levels as a screening test until there is more guidance in how an elevated level puts someone at risk for symptoms or other problems in the future. Similarly, an elevated anion gap was not helpful in defining anyone who had symptoms, nor helpful in defining those who had an elevated lactic acid. Thus, this test too cannot be recommended at this point. Similarly, if a lactic acid level is taken, it is not clear how much this test reflects a toxicity of the medications, as similar elevations were found in those who were not on medication. Much more work will need to be done to define a test that assesses which patients may be having mitochondrial dysfunction, and whether this dysfunction can be linked to medications.