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Hyperlactatemia in 20 Patients Receiving NRTI Combination Regimens J. T. LONERGAN*, D. HAVLIR, C. BEHLING, H. PFANDER, T. HASSANEIN, and W. C. MATHEWS.
Univ. California San Diego Med. Ctr Background/Objective: An often fatal syndrome of lactic acidosis and hepatic steatosis is a recognized but rare complication of NRTI therapy. We report a case series suggesting that there is a milder and possibly earlier form of the syndrome.
Methods: From 7/98 through 9/99 we identified 20 patients receiving NRTIs with unexplained hyperlactatemia plus either abdominal symptoms or an abnormal ALT.
Results: Mean (range) CD4+ cell count and plasma HIV-1 RNA were 370 cells/mm3 (23-1397) and 24,874 copies/ml (<40-427,360) respectively. All patients were receiving d4T, at least 1 other NRTI, and 18 were also receiving a PI (n=14) or NNRTI (n=7) with mean treatment duration of 12 months (range 4-22). Most common abdominal symptoms were pain (n=18), nausea (n=15) and distention (n=10). Mean peak venous lactate was 5.3 mmol/L. In 16 patients hyperlactatemia occurred in the absence of a combined drop in serum bicarbonate and increase in anion gap. All but 1 patient had an abnormal ALT. Mean ALT was 3.5 fold above normal. 5 patients had chronic hepatitis B or C. 6/7 liver biopsies showed steatosis. 3 patients were also diagnosed with concurrent NRTI-induced pancreatitis. All 20 patients survived and only 3 required hospitalization. Mean resolution time of hyperlactatemia after antiretrovirals were suspended was 62 days (range 7-176). The incidence of hyperlactatemia among patients on NRTI therapy (n=1285) in our clinic was 1.4 cases per 1000 person-months (95%CI:0.8-2.1). There were 0 cases in 6736 person-months of non-d4T containing NRTI therapy. The upper 95% confidence limit given 0 cases was 0.55 per 1000 person-months. 9 patients have resumed antiretroviral therapy without d4T for at least 3 months and have not had a recurrence of the syndrome.
Conclusions: Our observations extend the spectrum of the NRTI-induced lactic acidosis/hepatic steatosis syndrome by the identification of a subtler and perhaps an earlier presentation with characteristic symptoms and laboratory abnormalities, and favorable prognosis upon discontinuation of antiretroviral therapy. Increased use of d4T and combination NRTIs may contribute to the higher incidence observed in our population.
Key Words: Hepatic Steatosis, Lactic Acidosis, NRTI Toxicity
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