Allergic reaction to abacavir reported after treatment break, one year after starting the drug

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A woman has developed a hypersensitivity reaction to the nucleoside analogue abacavir (Ziagen) after restarting the drug after a treatment break. Investigators reporting the case in the January 23rd edition of AIDS believe that this case is unique as the woman had no symptoms of allergy to abacavir before treatment interruption, and because of the length of time the woman had been taking the drug prior to the development of the hypersensitivity.

The case involved a 27-year-old white woman who was diagnosed HIV-positive in 1995. In January 2002 she started a HAART regimen consisting of abacavir, 3TC and efavirenz. In March 2002 she stopped taking efavirenz after it was discovered she was pregnant, but continued taking abacavir and 3TC, which she continued to take throughout her pregnancy and after.

In April 2003 she changed her HIV treatment centre, at which time her CD4 cell count was 640 cells/mm3 and her viral load a little over 6,000 copies/mL. At this time treatment with abacavir and 3TC was stopped because of concerns about its lack of antiretroviral potency and the risk of resistance. A genotypic resistance test revealed the existence of the M184V mutation.

Glossary

hypersensitivity

An allergic reaction.

treatment interruption

Taking a planned break from HIV treatment, sometimes known as a ‘drugs holiday’. As this has been shown to lead to worse outcomes, treatment interruptions are not recommended. 

rash

A rash is an area of irritated or swollen skin, affecting its colour, appearance, or texture. It may be localised in one part of the body or affect all the skin. Rashes are usually caused by inflammation of the skin, which can have many causes, including an allergic reaction to a medicine.

genotypic resistance testing

In HIV, genotypic resistance tests are assays that identify mutations of the virus that can confer antiretroviral drug resistance. Resistance testing can be used to guide selection of an HIV regimen when initiating or changing antiretroviral therapy (ART). 

drug resistance

A drug-resistant HIV strain is one which is less susceptible to the effects of one or more anti-HIV drugs because of an accumulation of HIV mutations in its genotype. Resistance can be the result of a poor adherence to treatment or of transmission of an already resistant virus.

Therapy was restarted in May 2003 with abacavir, tenofovir and efavirenz. Within ten days the woman started to develop symptoms of hypersensitivity to abacavir, including malaise, a low-grade fever, nausea, vomiting and rash on the abdomen and extremities. Symptoms worsened for another ten days and the woman returned to her HIV clinic, at which time she had a fever of 100o, a resting heart-rate of 96 beats per minute and blood pressure of 126/82.

All symptoms rapidly disappeared after the woman stopped all anti-HIV therapy. A month later she restarted treatment with a regimen of ddI, tenofovir and efavirenz, and in July 2003 had a CD4 cell count of 669 cells/mm3 and a viral load below 400 copies/mL with no evidence of drug allergies.

The reuse of tenofovir and efavirenz in the later treatment regimen ruled out the possibility that the woman had a hypersensitivity to these drugs.

An analysis of 1,442 recorded cases of abacavir hypersensitivity reaction indicated that in seven cases patients experienced a hypersensitivity reaction to the drug after treatment interruption with no symptoms of allergy at the time of the treatment break.

To the best of the investigators’ knowledge, the case involving their patient was unique for three reasons. “(i)she had been on abacavir for more than one year with no side-effects; patients usually develop hypersensitivity 1 – 318 days after initiation; (ii) the reason for discontinuation was documented and related to drug resistance; (iii) the nature of the hypersensitivity reaction she developed after starting abacavir was more consistent with a denovo development of hypersensitivity reaction, in which symptoms normally develop within 10 days and worsen progressively.”

The investigators conclude that patients should be educated about the symptoms of abacavir hypersensitivity whenever they take a treatment break.

Further information on this website

Abacavir - overview

Abacavir hypersensitivity reaction experienced by 5% say GSK investigators - news story

Abacavir: can gene test predict fatal side-effect? - news story

Unusual abacavir hypersensitivity reported - initially diagnosed as throat infection - news story

References

Sahly HM et al. Development of abacavir hypersensitivity reaction after rechallenge in a previously asymptomatic patient. AIDS 18: 359 - 60, 2004