Azidothymidine eNS toxicity

III Hagler DN, Frame PT. Lancet 2: 1392·1393. 13 Dec 1986

Treatment with oral azidothymidine 200mg every 4 hours was initiated in a 41-year-old homosexual man with acquired immunodeficiency syndrome (AIDS). Previous anti-infective therapy for multiple opportunistic infections was discontinued. At the time of initiating azidothymidine therapy tests revealed WBC 2600/",1 with polymorphs 77% and lymphocytes 4%, Hb 9.0 g/dl, AST 76, AL T 43 and serum creatinine 1.4 mg/dl.

48 hours after beginning treatment, the patient complained of severe headache and was found unresponsive and lying on the floor of his house later that day.

Tonic-clonic activity of the left arm and leg was observed twice but no evidence of focal neurological lesions was present on admission and the patient responded to painful stimuli. No red blood cells, 1 white blood cell, protein 45 mg/dl and glucose 45 mg/dl were revealed after a lumbar puncture and mild atrophy without blood or mass lesions was observed on a computerised tomographic scan of the head. Responses increased over 24 hours, no further seizure activity occurred and within 48 hours the patient was alert and oriented, EEG was normal and there were no focal deficits.

Reintroduction of azidothymidine 200mg every 4 hours resulted in a slight headache 72 hours later which rapidly progressed to confusion, aphasia, left-sided weakness and intermittent twitching of the right-hand-side of the face and, more occasionally, the right arm and leg. IV lorazepam and phenytoin were administered but focal seizures continued over the following 12 hours. Respiratory arrest occurred 36 hours after the onset of neurological symptoms and the patient was not resuscitated.

'We recommend that AZT [azidothymidine] be used with extreme caution in patients with late manifestations of AIDS, who may be more susceptible to toxic side-effects of AZT because of eNS infection with HIV [human immunodeficiency virus] or opportunistic pathogens and/or may have altered AZT metabolism due to liver disease caused by opportunistic infections or the drugs used in their treatment.'

6 REACTION$® 10 Jan 1987 0157-7271/87/0110-0006/0$01.00/0 © ADIS Press