patient who developed MG in association with use of the HIV protease inhibitor, ritonavir. 4 This complication raises the concern that the frequent complaint of fatigue by ritonavir-treated patients may in some be related to development of MG.
Case Report. Over 7 days a 71-year-old man with an 8-year history of HIV infection and mild rheumatoid arthritis developed slurred speech, difficulty climbing stairs, and a change in facial appearance. Physical examination revealed slow slurred speech, bilateral ptosis, and lateral rectus weakness. All these signs worsened with prolonged testing. Intravenous injection of edrophonium produced improvement in eyelid elevation and speech. White blood cell count was normal and a recent CD4 count was 290 cells/mm 3 . Acetylcholine receptor and antinuclear antibody titers were not elevated. Routine electromyography was normal. Repetitive stimulation of the left facial and ulnar nerves at 3 Hz showed 23 and 18% decrements of the compound muscle action potentials (CMAPs). At 30-Hz stimulation no increment was evident. Computed tomography of the chest was normal. Three weeks prior to the onset of symptoms the patient had begun ritonavir 1200 mg daily. For at least 1 year he had been treated with AZT, 3TC, verapamil, and vitamin supplements. All medications were discontinued, and Mestinon started with significant improvement in all myasthenic manifestations. One week later 3TC and ddI were begun. Mestinon was stopped 1 month after development of first symptoms. Three months later mild ptosis and dysarthria were still present. Acetylcholine receptor antibody titers were negative. Repetitive stimulation of left facial and ulnar nerves at 3 Hz produced a 24 and 15% decrement of the CMAP. Mestinon was restarted.
Discussion. In association with the institution of ritonavir, the patient developed MG confirmed by electromyography and a response to edrophonium. A definite causal link cannot be established; however, the prompt improvement of MG manifestations after discontinuation of ritonavir suggests a relationship. Although ritonavir can elevate serum levels of verapamil, 4 and calcium channel blockers may exacerbate MG, the absence of hypotension makes this possibility unlikely. MG and coincident HIV infection are rare, and a direct pathogenic relationship is not clear. 2 Drugs may unmask MG by direct affects on neuromuscular transmission or by activation of an autoimmune response. 1 Since this patient had persistent evidence of MG 1 month after discontinuation of ritonavir, an immune modulatory affect is most likely. Previous descriptions of MG among HIV-infected patients demonstrate that MG manifestations tend to improve with reductions of T-cell numbers. 2 In this patient a transient improvement in immune function produced by ritonavir could have led to the development of MG.
The most common side effect of ritonavir is fatigue, the hallmark of MG. 3 Fatigue is also a common symptom among patients with HIV infection, and appreciation of MG may be difficult in such individuals. In the appropriate clinical setting, ritonavir-treated patients should be evaluated for MG.