Doubt cast on cost-effectiveness of HLA-B*5701 screening for Asian patients

No HIV-positive Korean patients tested positive for the gene associated with hypersensitivity to abacavir (Ziagen), investigators report in the February 1^st edition of Clinical Infectious Diseases. The study supports other research that found a very low prevalence of this gene in patients with an Asian ethnic origin, and the investigators question whether screening for abacavir allergy is cost-effective in Asian countries, “especially in a resource-limited healthcare setting”.

Allergy, or hypersensitivity, is a major side-effect of the anti-HIV drug abacavir (also in the combination drugs Kivexa and Trizivir). This hypersensitivity has been associated with the HLA-B*5701 gene and treatment guidelines recommend that patients being considered for treatment with abacavir should first have a test to see if they carry this gene. Individuals who test positive must not take abacavir. There have been rare cases of abacavir allergy in patients whose HLA-B*5701 result was negative, so it is important to watch for symptoms of abacavir allergy in these patients after starting treatment with the drug.

Individuals with a northern European ethnic background are the group most likely to have this gene. However, there has been little research into the prevalence of HLA-B*5701 amongst patients of Asian ethnicity.

The study involved all 534 Korean patients who received their HIV care at the University of Seoul, Korea, between 2003 and 2008. The investigators gathered information on the incidence of suspected abacavir hypersensitivity reactions in patients who initiated treatment with the drug and recorded whether this was subsequently confirmed by skin-patch testing.

HLA-B*5701 testing was introduced in the clinic in 2007. The researchers analysed the prevalence of positive results and they compared the prevalence of suspected abacavir hypersensitivity reactions in the period before and after testing was introduced.

None of the patients tested positive for HLA-B*5701.

A total of 150 individuals were treated with a combination of anti-HIV drugs that contained abacavir. Of these, 57 (38%) did so without a prior test for allergy to the drug. A total of 15 patients (10%) stopped treatment with abacavir within the first six weeks, and seven of these patients did so because of a suspected abacavir hypersensitivity reaction.

The investigators noted that there was no difference in the prevalence of patients stopping abacavir treatment because of suspected hypersensitivity reactions in the periods before (5%) and after (4%) screening was introduced.

Skin patch tests were performed on all the patients who discontinued abacavir because of suspected hypersensitivity. All these tests were negative, confirming that none of the patients had had an actual allergic reaction to the drug.

“The present study demonstrated that HLA-B*5701 was significantly less common (0%) in HIV-infected Koreans than in US Caucasians (6%-8%) and African Americans (2.5%)”, write the investigators.

They note that their findings are consistent with earlier research that has found HLA-B*5701 prevalences below 0.5% in Chinese, Korean, Japanese and Taiwanese patients. But they emphasise that studies have found higher prevalences of the gene in Indian (5%-20%) and Thai (4%-10%) patients.

“HLA-B*5701 screening is supposed to be useful even in countries with a low prevalence of HLA-B*5701, because it may reduce clinical overdiagnosis of abacavir hypersensitivity reactions”, note the investigators. However, they question if this is actually the case as comparable proportions of patients stopped treatment with suspected abacavir allergy before and after screening was introduced. None of these patients had a positive skin patch result.

The investigators therefore express doubts about the cost-effectiveness of routine HLA-B*5701 screening in regions like Korea with a low prevalence of the gene.

They propose an alternative strategy, writing “clinical observation could replace the HLA-B*5701 screening test, especially in a resource-limited health care setting. In that case, the skin patch test could be used to retrospectively confirm abacavir hypersensitivity in patients who are clinically suspected of, or whose symptoms are ambiguous with regard to, abacavir hypersensitivity.”