Serum L-lactate and pyruvate in HIV-infected patients with and without presumed NRTI-related adverse events compared to healthy volunteers.
BACKGROUND
Nucleoside reverse transcriptase inhibitors (NRTIs) used in antiretroviral therapy may cause mitochondrial toxicity. Mitochondrial dysfunction leads to disturbance of the glucose metabolism, resulting in an accumulation of L-lactate (L) and pyruvate (P), with an enhanced L/P ratio.


OBJECTIVE
We analysed lactate and pyruvate blood samples of patients of our outpatient department. Aim of the analysis was to detect preliminary mitochondrial toxicity in patients on antiretroviral nucleoside analogues, which might result in disturbances of L, P, L/P ratio, bicarbonate (Bic) or beta-hydroxybutyrate/aceto-acetate (beta-HB/AA) ratios.


METHODS
Blood samples of L, P, Bic, beta-HB and AA were analysed in four groups of subjects. The first group (A) consisted of patients with presumed NRTI-related adverse events (n=21), the second group (B) consisted of patients without adverse events (n=28), the third group (C) were HIV-infected patients without antiretroviral therapy (n=6) and the last group (D) were healthy controls (n=12). The mean duration of NRTI-treatment was 18 months (range 0-78 months).


RESULTS
The mean lactate level in group A was 2319 micromol/l (S.D. +/-1231, median 1741 micromol/l), in group B 1257 micromol/l (S.D. +/-607, median 1087), Group C 1285 (S.D. +/-451, median 1245 micromol/l) and 951 micromol/l (S.D. +/-270, median 979) in the healthy controls. No significant differences in pyruvate, L/P, Bic and beta-HB/AA were seen in the four groups. The mean lactate level in patients on stavudine was 1980 micromol/l (S.D. +/-1197) versus 1051 micromol/l (S.D. +/-395, P=0.01) in patients on zidovudine. All patients with lactate values above 2700 micromol/l (eight) experienced adverse events.


CONCLUSIONS
Lactate levels were higher in patients with presumed NRTI-related adverse events. Furthermore, HIV patients receiving a stavudine containing antiretroviral therapy had higher lactate values than patients without stavudine. Although routine lactate measurement in all patients on antiretroviral therapy is not recommended, lactate measurement might be useful for follow up of patients with presumed NRTI-related adverse events and in patients with lactate levels above 2500 micromol/l. These patients require extra surveillance to evaluate if discontinuation of the current antiretroviral therapy is needed.
ter Hofstede
Hadewych J M
HJ
Department of Internal Medicine, University Hospital Nijmegen StRadboud, PO Box 9101, 6500 HB Nijmegen, Netherlands. h.teerhofstede@aig.azn.nl
Willems
Hans L
HL
Koopmans
Peter P
PP
D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000627:therapeutic use; D004272:DNA, Mitochondrial / Q000187:drug effects; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1; D006801:Humans; D019344:Lactic Acid / Q000097:blood*; D008297:Male; D008928:Mitochondria / Q000187:drug effects; D019289:Pyruvic Acid / Q000097:blood*; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D018119:Stavudine / Q000009:adverse effects* / Q000627:therapeutic use; D015215:Zidovudine / Q000009:adverse effects* / Q000627:therapeutic use
D019380:Anti-HIV Agents; D004272:DNA, Mitochondrial; D018894:Reverse Transcriptase Inhibitors; D019344:Lactic Acid; D015215:Zidovudine; D019289:Pyruvic Acid; D018119:Stavudine