Need for vigilance: two cases of abacavir allergy despite pre-treatment screening all-clear

Healthcare workers and patients need to be vigilant about the possibility of an allergic reaction after starting abacavir (Ziagen), even if the HLA-B*5701 screening test is negative, emphasise investigators in separate reports in the July 31^st edition of AIDS.

It is now well known that abacavir can cause a severe allergic reaction in about 8% of patients. Symptoms include rash, fever, stomach or chest problems. Most cases occur within six weeks of starting treatment with the drug.

Research has found an association between hypersensitivity to abacavir and the presence of the HLA-B*5701 gene. This gene is most common among, but not limited to, individuals with a northern European racial origin.

It is possible to test patients for the presence of this gene, and only patients with a confirmed negative result should start treatment with abacavir.

But doctors in London provided care to a patient who developed an usual hypersensitive reaction to abacavir, despite being HLA-B*5701-negative.

The case involved a 45-year-old Kenyan man. He was diagnosed with tuberculosis and subsequently HIV. At the time of his HIV diagnosis his CD4 cell count was 70 cells/mm³ and his viral load 500,000 copies/ml. A test at this point also showed that the patient was HLA-B*5701- negative.

Standard four drug tuberculosis treatment was provided to the patient, and within five days the patient’s temperature had returned to normal. Five weeks later anti-HIV drugs were started.

Considerable care was taken to ensure that the patient’s anti-tuberculosis drug and HIV treatment regimen did not interact. He therefore initiated antiretroviral therapy with a highly unusual combination of AZT, Truvada (tenofovir and FTC), and abacavir.

Within five hours of receiving his first dose of anti-HIV drugs, the patient developed a fever of 39 degrees C, and felt generally unwell, nauseous, and had abdominal pain. There was no rash. With the exception of the fever, these symptoms disappeared. However for the next 13 days the patient had a temperature above 39 degrees C.

A range of tests were conducted to see if the patient’s high temperature was due to a cancer or infection. These investigations found nothing significant.

Sixteen days after antiretroviral therapy was started, the patient’s doctors decided to eliminate a drug allergy as a possible cause of the fever. Treatment with abacavir was therefore stopped and a new antiretroviral regimen consisting of Combivir (3TC and AZT), tenofovir, and Kaletra (lopinavir/ritonavir) was started.

Within hours the patient’s temperature returned to normal. Treatment with anti-tuberculosis drugs was continued and three weeks later the patient was still without a fever and had a CD4 cell count of 160 cells/mm³ and a viral load of 500 copies/ml. A second HLA-B*5701 test was negative

The investigators suggest that this case raises three important issues:

• This is the first case to involve such a rapid onset of the symptoms of abacavir hypersensitivity and (with the exception of the fever) such a quick recovery. They note that abacavir is quickly absorbed and that this could explain the rapid appearance of the fever.
• This is the most severe report of abacavir hypersensitivity in an HLA-B*5701-negative individual.
• This case could represent an unusual hypersensitivity reaction to the drug.

But the investigators acknowledge that they did not perform a skin-patch test to confirm their diagnosis of an abacavir hypersensitivity reaction.

“Overall, this case demonstrates that not all abacavir drug reactions occur as a result of classic hypersensitivity reactions and can occur irrespective of HLA-B*5701 status”, write the investigators. They conclude, “as such, clinical vigilance must continue to be an essential part of the management of individuals commencing abacavir.”

A separate case report in the same edition of AIDS concerns a severe abacavir hypersensitivity reaction, also in an HLA-B*5701-negative patient.

Doctors in Amsterdam report that their patient had both negative HLA and skin patch tests, but nevertheless developed symptoms including a breakdown of muscle fibres (rhabdomyolysis), muscle aches, watery diarrhoea and a high temperature. These symptoms had developed ten days after the patient replaced AZT with abacavir in his antiretroviral regimen.

Anti-HIV therapy was stopped because of the symptoms and the patient slowly recovered. HLA-B*5701 tests were negative before the patient started abacavir therapy and after treatment with the drug was stopped. The results of an abacavir skin patch test were also negative.

“Even if a patient is tested HLA-B*5701 or skin patch negative or both, severe abacavir hypersensitivity reaction can still occur, and prudent clinical management remains necessary”, write the investigators. They conclude that although the HLA-B*5701 gene has been strongly associated with hypersensitivity to abacavir, “a second mechanism might be involved, and future…testing for abacavir hypersensitivity is open for improvement.”