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Session 18 Oral Abstract Presentations
Viral Neuropathogenesis
Session Day and Time: Wednesday 10 am - 12:30 pm
Presentation Time: 10:15
Room: Ballroom C


87
HIV-associated Neuromuscular Weakness Syndrome
D. Simpson*1, L. Estanislao1, K. Marcus3, M. Truffa3, J. McArthur4, B. Lucey4, D. Dorfman1, R. Naismith5, I. Guerrero6, J. Mendez6, T. Lonergan7, Y. Landau8, M. Harris9, J. Montaner9, D. Clifford5
1Mt Sinai Med Ctr, New York, NY; 3FDA, Bethesda, MD; 4Johns Hopkins Univ, Baltimore, MD; 5Washington Univ Sch of Med, St Louis, MO; 6Univ of Miami, FL; 7Univ of California at San Diego; 8Nassau County Med Ctr, Long Island, NY; and 9British Columbia Ctr for Excellence in HIV/AIDS, Vancouver, Canada

Background: There have been reports of progressive, severe neuromuscular weakness and hyperlactatemia associated with nucleoside reverse transcriptase inhibitor antiretroviral therapy (NRTI). We performed an analysis of such cases, with focus on neurological, electrophysiological, pathological, and metabolic features.

Methods: Cases of HIV-associated neuromuscular weakness syndrome

(HANWS) were retrospectively identified. They were classified as possible, probable, or definite based on the availability of a documented neuro-medical evaluation, to exclude confounding causes of weakness (probable), or electrophysiologic, and/or pathologic confirmation of neuromuscular pathology (definite). Differences between groups were analyzed with ANOVA.

Results: There were 55 patients (pts) with HANWS (17 possible, 15 probable, and 23 definite). The most commonly used antiretroviral (ARV) agent was stavudine (d4T, n = 44). The three groups did not differ in terms of age, serum lactate and bicarbonate (HCO3) levels, arterial pH, CD4 count, and HIV viral load. In the definite cases with documented lactate levels, 17/20 were elevated (mean 8.4 mmol/L), and 9 cases had metabolic acidosis (mean HCO3 = 12.9 meq/L, median pH = 7.1). Electrophysiologic and pathologic findings revealed axonal neuropathy in 12 cases and myopathy in 2. Of 12 muscle biopsies, 2 revealed inflammation, and 2 mitochondrial abnormalities. The mean duration of d4T use was higher in those with neuropathy (18.8 months) compared to those with myopathy (6.7 months; p = 0.009). In 10 cases with documentation of the timing of symptom onset, there was a substantial delay between the systemic symptoms of hyperlactatemia or diagnosis of lactic acidosis syndrome, and the onset of neurological symptoms (mean interval = 26 days). In 14 pts, there was also a time lag between the cessation of ARV therapy and the onset of neurologic symptoms (mean interval, 12 days). Of 36 pts with documented follow-up, 14 required intubation and 9 died.

Conclusion: A progressive neuromuscular weakness syndrome occurs in the setting of HIV infection and NRTI therapy. Associated hyperlactatemia and discontinuation of ARV may precede the onset of neurological symptoms, suggesting different etiological mechanisms of these disorders.