4th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV 22-25 September 2002, San Diego, CA, USA

LACK OF RECURRENCE OF SYMPTOMATIC AND ASYMPTOMATIC HYPERLACTATEMIA WHEN STAVUDINE IS REPLACED BY EITHER ABACAVIR OR ZIDOVUDINE: 48-WEEK DATA

Antiviral Therapy 2002; 7:L13 (abstract 21)

T Lonergan¹, G McComsey², S Hessenthaler³, P Shalit⁴, T File⁵, V Williams³, and J Hernandez³ for the ESS40010 (TARHEEL) study team
¹UCSD Antiviral Research Center, San Diego, Calif., USA; ²Case Western Reserve, Cleveland, OH, USA; ³GlaxoSmithKline, Research Triangle Park, NC, USA; ⁴Swedish Medical Center, Seattle, Wash., USA; ⁵Summa Health System, Akron, OH, USA

OBJECTIVES: Symptomatic hyperlactatemia (≥2.2 mmol/l) is a rare complication of nucleoside reverse transcriptase inhibitor (NRTI) use. Clinical features include nausea/vomiting, anorexia/weight loss, abdominal pain/bloating, dyspnea, fatigue and tachycardia. Unexplained elevations of AST, ALT and anion gap are usually present. Early detection/treatment of symptomatic hyperlactatemia may prevent progression to fatal lactic acidosis and hepatic steatosis. TARHEEL was designed to assess the reversibility of lipoatrophy and hyperlactatemia following substitution of stavudine with either abacavir or zidovudine. The following analysis presents final 48-week data, emphasizing 16 subjects who enrolled with hyperlactatemia (ITT, Observed).

METHODS: Subjects with HIV-1 RNA <400 copies/ml on stavudine-containing regimens for ≥6 months, with lipoatrophy, symptomatic hyperlactatemia or both were eligible. Most subjects with hyperlactatemia discontinued antiretroviral therapy (ART) at screening. Once lactates normalized, ART was resumed with either abacavir or zidovudine replacing stavudine at baseline. Lactate changes were assessed via laboratory values and symptoms via self-reports.

RESULTS: One hundred and eighteen subjects were enrolled; 86/118 replaced stavudine with abacavir and 32/118 with zidovudine. Sixteen subjects had screening lactates ≥2.2 mmol/l; 12/16 replaced stavudine with abacavir and 4/16 with zidovudine. Ten out of 16 discontinued ART for a median of 31 days; six switched directly to abacavir or zidovudine. Hyperlactatemia subjects had median lactate levels at screening, baseline and week 48 of 2.9, 2.1 and 1.3 mmol/l, respectively. At week 48, median changes from baseline in lactate, AST, ALT and anion gap were -0.80 (P=0.05), 0 U/l, -6.50 U/l and -2.50 mEq/l. At screening, 6/16 subjects reported ≥1 clinical symptom. By week 48, 1/13 reported a reduction in nausea/vomiting/anorexia; 1/13 reported improvement in abdominal pain/bloating. The entire cohort had a median baseline lactate of 1.4 mmol/l; 52/116 reported ≥1 clinical symptom. At week 48, the median change in lactate was -0.15 (P=0.0015). Ten of 102 and 11/102 experienced a reduction in nausea/vomiting/anorexia and abdominal pain/bloating. At 48 weeks, all subjects with hyperlactatemia and 93% of entire cohort had HIV-1 RNA <400 copies/ml. Seventeen serious adverse events and eight cases of abacavir-hypersensitivity were reported across all subjects.

CONCLUSIONS: Subjects with NRTI-induced hyperlactatemia showed early and sustained improvements in laboratory markers, without recurrence, when stavudine was replaced by either abacavir or zidovudine.

Presenting author: T Lonergan

2002-09-22
21

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