Rash-associated severe neutropenia as a side-effect of indinavir in HIV postexposure prophylaxis.

Abstract

A 33-year-old female surgical resident received a needlestick injury while inserting an intravenous line into an HIV-positive patient. The index patient was known to be HIV-positive for over 7 years, had had an episode of Pneumocystis carinii pneumonia 6 years ago and another episode 2 years ago, and was currently being treated for a suspected recurrence of a lymphoma first diagnosed 5 years ago. His latest viral load was 5000 copies/ml 6 months ago, and the latest CD4 T cell count was 85 cells/μl 1 year ago. He was currently on antiretroviral treatment with saquinavir, zidovudine and lamivudine, but had received and failed multiple other treatment regimens previously. The surgeon had previously been in good health, with no relevant medical history, specifically no history of adverse drug reactions or allergies. Her only medication consisted of a hormonal contraceptive, a combination of desogestrel and ethinylestradiol in cycle-dependent dosing, which she had been taking continuously for over 2 years. The injury caused by the contaminated needle proved to be a deep scratch on the lower left arm, just proximal of the rubber glove the surgeon had been wearing. Immediately after the incident, a local antiseptic was applied to the wound. Physical examination revealed no other abnormal findings at this time. In accordance with current German Guidelines for HIV Postexposure Prophylaxis [1], therapy with zidovudine (300 mg twice a day), lamivudine (150 mg twice a day) and indinavir (800 mg every 8 h) was started in the surgeon 2 h after the incident. Apart from nausea, the medication was initially well tolerated. On day 5 after the incident she developed fever up to 39°C and headaches; on examination, no lymphadenopathy, rash or other findings were noted. On day 7, these complaints improved. On the evening of day 9, a generalized maculopapular rash was noted, rapidly progressing over night, in conjunction with a strong itch and nausea. On day 10, indinavir was stopped after the morning dose; in the evening nelfinavir was started at a dose of 1250 mg twice a day. The results of the full blood count from day 10 showing severe neutropenia only became available during day 11; as a result, zidovudine was also paused after the morning dose, leaving a prophylaxis medication of nelfinavir and lamivudine only. However, on the evening of day 12, when an improvement in the neutropenia became apparent, zidovudine was restarted. The rash visibly improved on day 16 and had completely disappeared by day 24. The results of the full blood counts are summarized in Table 1. Haemoglobin, thrombocytes, sodium, potassium, creatinine, transaminases, lactate-dehydrogenase, creatine kinase and glucose were within the normal range; lipase was mildly elevated on days 10 and 12 with 70 and 73 U/l, respectively, and normalized again by day 24. HIV serology was negative on days 1, 29, 83 and 191; HIV polymerase chain reaction was negative on day 43. Apart from the symptoms described, the patient remained in good health; in particular, no evidence of secondary infections appeared at any time.Table 1: Results of the full blood counts.When it became apparent that a imbalance between neutrophils and lymphocytes persisted, a cytological examination of peripheral blood cells was performed on day 198. A completely normal morphology of all leukocytes was seen, including an immunocytologically normal relationship of T and B cells; thus, a bone marrow biopsy was deferred. Rash is a known side-effect of indinavir [2]. There are, however, no previous reports of neutropenia in association with indinavir therapy, neither as a treatment nor as prophylaxis for HIV infection. Although there are numerous reports of haematological side-effects of zidovudine, among them cases of neutropenia with prophylactic zidovudine use [3], we believe that a zidovudine effect can be ruled out in this case because of a clear improvement of the neutropenia after the discontinuation of indinavir and only a brief interruption of zidovudine. It should be noted that although a previous differential blood count was completely normal, a relative imbalance between neutrophils and lymphocytes persisted in our patient for over half a year after the episode of neutropenia. Whether this represents a pre-existing and thus possibly predisposing condition such as a myeloic stem cell disease, an effect of another agent transmitted at this or another occasion, or a persisting toxic effect of indinavir remains unclear. Examinations will be repeated regularly on the patient. In summary, we observed a case of severe neutropenia in association with rash as a side-effect of indinavir intake for postexposure prophylaxis after percutaneous HIV exposure. We conclude that a differential blood count should be performed regularly in patients on indinavir, especially when other side-effects appear.