Use of HLA-B*5701 genetic testing to reduce abacavir hypersensitivity reactions

Several studies presented data relating to the use of the newly available HLA-B*5701 genetic test, which has the potential to identify people most at risk for abacavir-related hypsersensitivity reactions (HSR).

Iain Reeves from Brighton NHS Trust, presented updated results from a study first presented at CROI this February. This new analysis, more than tripled the number of tests, allowing a better calculation of the statistical significance of the results. [1]

These results, from a prospective study in 390 patients using B*5701 prior to starting or changing treatment, and more recently, newly diagnosed patients, compared HSR rates to historical data from their clinic cohort. This was a largely white, male population: males = 249 (92%), females = 22 (8%); white = 215 (79%), black = 42 (15%), other ethnicity = 11 (4%), not known = 3 (1%).

Overall, positive results occurred for 31 patients (8%); 27/307 (9%) in whites and 4/58 (7%) in blacks. These differences are important as HLA-B*5701 frequency varies considerably between racial groups: 0-1% Japan, China, Africa, US Asia; 1-2% Mediterranean and Middle East; 2.5% African/American; 8% UK, US white, Australian; 5-20% India) [2]. Abacavir HRS is also reported less frequently in African/Americans.

Only 106/259 patients with negative B*5701 results (90 white, 13 black, 3 other) subsequently started abacavir (largely because B*5701 screening is now routine in Brighton, and many patients did not need to change or start treatment). However, the HSR rate in this group was 0 (95% CI 03.5%) compared to historical rate of 20/322 = 6.5% (95% CI 4.19.4%) prior to B-5701 testing (P=0.01). Historically, HSR has not been reported in black patients at this clinic, but the study highlighted that while the positive results for black patients was much higher than population data would suggest, the numbers in this study are too small to comment on specificity and sensitivity.

Three case studies were presented in a poster from Des Maitland and colleagues at the Chelsea and Westminster Hospital, where HLA-B*5701 testing has been introduced, with results supported by skin-patch testing. [3]

The first case was a 63 year old white man who presented with macular rash 17 weeks after starting abacavir, which resolved on stopping treatment and returned as generalised rash when abacavir was reintroduced. Results from skin-patch test were equivocal, but later testing with B*5701 was positive.

A second case was a 37 year old white male who tested negative for B*5701 and developed symptoms of fever, rash, nausea, shortness of breath and muscle pain, seven weeks after starting abacavir, and which resolved within 48 hours of discontinuing abacavir.

The third case was a 59 year old white male who tested negative for B*5701 and who developed fever, nausea and muscle pain, 3 weeks after starting abacavir, which resolved within 24 hours of stopping abacavir.

Comment

From the perspective of the Brighton clinic, using B*5701 testing (costing approximately £50) has had a major impact on the frequency of HSR, and increased the confidence of both clinicians and patients in using abacavir.

The researchers acknowledge that it is clearly important to generate more data on non-white patients.

The case studies from Maitland and colleagues highlight that a negative result should not exclude the possibility of HSR, and that careful patient management is still crucial.