Hypersensitivity reactions to abacavir occur in approximately 5% of treated individuals, and may be manifested by fever, rash, constitutional complaints, gastrointestinal disturbances and hematological abnormalities [1]. These reactions can be life-threatening particularly if patients are re-challenged with abacavir [2]. The presence of HLA-B*5701 has been associated with a higher risk of abacavir hypersensitivity reactions in Caucasian and Hispanic populations [3,4]. To date, no other nucleoside reverse transcriptase inhibitors have been reported to cause similar hypersensitivity reactions. We report a case of an emtricitabine/tenofovir hypersensitivity reaction. An 18-year-old African American man with a CD4 cell count of 322 cells/μl and an HIV-1-RNA viral load of 4550 copies/ml was admitted to the hospital with a 2-day history of fevers to 103.6°F, fatigue, myalgias, conjunctival infection and non-bloody diarrhea. He denied nausea or vomiting but had a poor appetite over this time. Ten days previously, he had entered a randomized clinical trial for antiretroviral-naive patients. He initiated open-label treatment efavirenz and blinded treatment with emtricitabine/tenofovir (or placebo) or abacavir/lamivudine (or placebo). The patient's physical examination revealed a temperature of 102.2°F and orthostatic hypotension. His laboratory findings were significant for an elevated white blood cell count of 17 000 cells/μl, blood urea nitrogen level of 23 mg/dl, and creatinine level of 1.4 mg/dl. Intravenous fluids and broad-spectrum antibiotics were administered. HIV medications were withheld. Blood, urine and stool cultures were negative, and a computed tomography scan of the abdomen and pelvis was normal. The patient recovered and went home after 4 days with suspected bacterial gastroenteritis on ciprofloxacin and metronidazole. The patient returned to the study unit the day after discharge and received his study medications under direct observation. Within one hour, he complained of a headache and numbness of his hands and feet. He then had projectile vomiting and was subsequently found to have a systolic blood pressure of 70 mmHg and a heart rate of 140 beats a minute. Physical examination showed early desquamation of his scalp and face. The patient was transferred to the medical intensive care unit where he received intravenous fluids and brief hemodynamic support with vasopressors. All cultures remained negative. HIV medications were withheld, and he recovered after 4 days. The patient was diagnosed clinically with an abacavir hypersensitivity reaction. The unblinding process revealed that he had been randomly selected to receive emtricitabine/tenofovir. Mass spectroscopy of the dispensed medications confirmed that the patient's pills indeed contained emtricitabine/tenofovir. The patient was subsequently given zidovudine/lamivudine and efavirenz without further problems. Abacavir hypersensitivity is a potentially fatal syndrome with a multisystemic presentation [1]. Our patient presented within 10 days of initiation of his medications and exhibited many features similar to those reported with abacavir hypersensitivity, including fever, myalgias, fatigue, diarrhea, rash and hypotension. His symptoms resolved rapidly after discontinuing the medications and became much more severe upon rechallenge. The initial assessment by the caring physicians was that he had an acute febrile illness, probably viral or bacterial in origin, and that it would be safe to resume his antiretroviral therapy. We believe this is one of the first reports of a systemic emtricitabine/tenofovir hypersensitivity reaction. We cannot discern which drug might have induced this reaction. The patient was successfully given lamivudine subsequently, which is chemically similar to emtricitabine [5]. In a recent research letter, Lockhart described nine patients with suspected tenofovir cutaneous hypersensitivity reactions, all manifesting as maculopapular or vesicular rashes [6]. Only one of their patients appeared to have a more systemic illness that included urticaria, shortness of breath, and angioedema. Our patient did not present with either a maculopapular or vesicular rash, but did have desquamation of his scalp and face. He had more of a systemic illness that involved gastrointestinal symptoms, fever, and hypotension, similar to the reaction seen with abacavir hypersensitivity. We thus suspect that this patient had a systemic reaction to tenofovir. Clinicians should consider hypersensitivity reactions in patients taking nucleoside or nucleotide reverse transcriptase inhibitors who present with a systemic illness. Hypersensitivity reactions similar to those described with abacavir may occur with other nucleoside reverse transcriptase inhibitors. It may be prudent to hold these medications upon presentation and exercise caution with rechallenge. Sponsorship: This work was supported by ACTG training grant U01069513-01. Conflicts of interest: C.J.F. has received honoraria and research grants from Gilead Sciences, Inc.
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Feb 12, 2009
Claudia Constantin + 5
Open Access