Acute Hypersensitivity with Delavirdine

Abstract

Delavirdine is an antiretroviral drug now being used as part of combination antiretroviral therapy for the management of human immunodeficiency virus (HIV) infection [1]. It belongs to the non-nucleoside reverse transcriptase inhibitor class of drugs. These drugs are known to induce delayed-type hypersensitivity skin reactions as their commonest toxicity [2]. We would like to report a severe anaphylactic reaction to delavirdine in one of our patients. The patient is a 30-year-old HIV-positive male who was first found to be HIV-positive in January 1991, and has had a number of antiretroviral therapies over the subsequent 6 year period, including zidovudine, zalcitabine, lamivudine and saquinavir. He had no known drug allergies. In December 1997, when the patient was on zidovudine, lamivudine and saquinavir, a decision was made to commence the patient on an alternative regimen because his CD4 count had fallen to 340 cells/mm3 and his viral load had risen to 78000 copies/ml from a nadir of 5900 copies/ml. Unfortunately, the patient decided to discontinue all antiretroviral therapy and his CD4 count subsequently fell to 200 cells/mm3 with his HIV viral load increasing rapidly to 760000 copies/ml. In February, as part of a clinical trial, he commenced therapy with soft gel saquinavir 800 mg three times daily, stavudine 40 mg twice daily, didanosine 400 mg daily and delavirdine 400 mg three times daily. Within 3 days of commencement of the delavirdine he developed an erythematous maculopapular rash on his face and trunk which subsequently spread to his arms and knees, becoming confluent and involved all parts of the body except the upper chest. There was no initial desquamation. The drugs were discontinued 1 week after the commencement of the rash. On discontinuation of the drugs the rash resolved completely over the next 4 days and 1 week later he recommenced one 200 mg dose of delavirdine. At this time he was also receiving intravenous amoxycillin/potassium clavulanate, morphine, metoclopramide and paracetamol. One hour after his delavirdine dose he developed an itchiness over his body followed within the next 2 h by tightness in his chest, difficulty breathing and a red confluent rash over his whole body. The shortness of breath and chest tightness intensified and the patient became extremely distressed. Inspiratory wheezes were noted, pulse was 85/min, oxygen saturation was 97% and blood pressure 120/75 mmHg. During the period of respiratory distress, the patient’s pulse, blood pressure and oxygen saturation remained stable (pulse 90, BP 120/80, saturation 97%). The patient did not respond to phenergan or hydrocortisone but responded quickly to adrenalin and his breathing settled markedly within 40 min and subsequently resolved back to his normal respiratory status within 24 h. The rash that subsequently developed desquamated on his face, hands and legs. We believe that the skin rash and anaphylactic reaction is a side-effect of delavirdine, and wish to alert physicians to the possibility of such severe reaction on rechallenge. Subsequently the patient has recommenced stavudine, didanosine, soft gel saquinavir and nelfinavir without any side-effects. His CD4 count has climbed from 200 to 620 and his viral load has fallen to 2900 copies/ml within 2 weeks of commencing his new regimen. While delayed-type hypersensitivity reactions have been commonly reported with this class of antiviral, immediate anaphylactic reactions appear rare. Caution should be used when considering rechallenging patients with possible delavirdine rashes.