Doctors in United States have reported a suspected hypersensitivity reaction to tenofovir (Viread). The case in described in the October edition of AIDS and the authors recommend “clinicians should consider hypersensitivity reactions in patients taking nucleoside or nucleotide reverse transcriptase inhibitors who present with systemic illnesses.”
Severe allergic reactions occur in between 5% and 8% of patients treated with abacavir (Ziagen) with symptoms including fever, rash, stomach problems and blood abnormalities. A hypersensitivity reaction to abacavir can be life-threatening if a patient discontinues treatment with the drug after it develops and then takes the drug again.
Tests for the HLA-B*5701 gene can predict which patients have a risk of experiencing a hypersensitivity reaction to abacavir, and it appears that this gene occurs most frequently in patients of northern European genetic origin.
Kivexa, abacavir combined with 3TC (lamivudine, Epivir) is one of the nucleoside backbones recommended for first-line antiretroviral therapy in many treatment guidelines. An alternative backbone is Truvada, tenofovir combined with FTC (emtricitabine, Emtriva), and this option is attractive because it has not previously been associated with a hypersensitivity reaction.
However, doctors in Ohio have now reported a case of a suspected hypersensitivity reaction in a patient taking Truvada.
The case involved an 18 year-old African American male who was admitted to hospital with a two-day history of a fever of 104 degrees F, fatigue, muscle pain, eye infection and diarrhoea. Ten days before he had entered an open label trial of efavirenz with blinded FTC/ tenofovir (or placebo) or abacavir/3TC (or placebo).
Blood tests showed that the patient had an elevated white blood count of 17,000 cells/ml, a blood urea nitrogen level of 23mg/dl and a creatinine level of 1.4mg/dl.
Urine, stool and blood cultures were all negative and a scan of the abdomen and pelvis was normal.
All anti-HIV medication was withheld and treatment with broad-spectrum antibiotics and intravenous fluids was administered as a bacterial stomach infection was suspected. The patient was discharged from hospital after four days with ciprofloxacin and metronidazole to treat the suspected stomach infection.
On the day after leaving hospital, the patient returned to the centre conducting the clinical trial he was registered on and was provided with his study medication under observation. Within an hour, he developed a headache, numbness in the hands and feet and projectile vomiting.. Doctors also noticed that the patient’s skin was flaking from his scalp and face.
The patient was transferred to intensive care and his HIV medication was withheld, and after four days he recovered. All his cultures remained negative and he was diagnosed as having experienced an abacavir hypersensitivity reaction.
However, the unblinding of the patient’s clinical trial revealed that the patient had, in fact, been receiving treatment with FTC/tenofovir. He was switched to AZT/3TC (Combivir) with efavirenz and experienced no further problems.
“We believe this is one of the first reports of systemic emtricitabine/tenofovir hypersensitivity reaction”, write the investigators. Although they cannot be certain which drug in the FTC/tenofovir combination caused the reaction seen in their patient, they note a hypersensitivity reaction to tenofovir involving the skin has previously been reported in nine patients (Lockhart, 2007). These patients developed rashes. Although their patient did not develop a rash, he did experience flaking of the skin from the face and scalp and had systemic symptoms “similar to the reaction seen with abacavir hypersensitivity. We thus suspect that this patient had a systemic reaction to tenofovir.”
The investigators caution that hypersensitivity reactions similar to that seen with abacavir may occur with other NRTIs, concluding, “it may be prudent to hold these medications upon presentation and exercise caution with rechallenge.”
De Perio MA et al. A Truvada hypersensitivity reaction simulating abacavir hypersensitivity. AIDS 21: 2252 – 2253, 2007.
Lockhart S et al. Cutaneous reactions with tenofovir disoproxil fumarate: a report of nine cases. AIDS 21: 1370 – 1373, 2007.