Clinical Utility of HLA-B*5701 Testing in a UK Clinic Cohort
Iain Reeves*, M Fisher, and D Churchill
Brighton and Sussex Univ Hosp NHS Trust, Brighton, UK
Background: Recently zidovudine (AZT) therapy has been recognized as a risk
factor for the development of lipoatrophy in HIV-infected patients. Tenofovir (TDF)
and abacavir (ABC) are alternative nucleosides without this concern and
available in convenient fixed-dose combination formulations. Historically the
use of ABC has been less attractive because of its association with a
hypersensitivity reaction. HLA-B*5701 is strongly associated with ABC
hypersensitivity; by genotyping individuals before starting or changing therapy
the incidence of this adverse event may be considerably reduced.
Methods: A prospective study of B*5701 testing in patients starting or
switching HAART. ABC was avoided in those testing positive for this allele and
the safety of ABC use in those testing negative was assessed. Hypersensitivity
reaction rates in the latter subjects were compared with the rate in those
starting ABC prior to B*5701 testing. Rates were compared using Fisher’s exact test and 95% confidence
intervals were calculated using Hanley’s rule of 3 approximation.
Results: Of 114 patients tested, 16 (14%) were positive. Gender and ethnicity
were as follows: males = 93 (82%),
females = 21 (18%); black = 23 (20%), white = 87 (76%), other ethnicity = 4
(4%). The carriage rate was 14 of 87 = 16% in whites and 2 of 23 = 9% in blacks.
Of the total, 40 patients were naïve or re-starting therapy and 73 were
considering switching (68 of the latter were on a thymidine analogue); 38
patients subsequently started ABC with an hypersensitivity reaction rate of 0
(95%CI 0 to 13%) compared with 14 of 320 = 4% hypersensitivity reaction rate
prior to B*5701 testing. This comparison failed to reach significance at this
point but as more B*5701 negative patients start ABC the confidence interval is
expected to narrow considerably.
Conclusions: This is one of the first studies to report on B*5701 carriage rate
in a U.K.-based clinical cohort. The carriage rate is higher than reported in
other studies. Incorporating this strategy into routine clinical practice is
likely to lead to significant enhancements in patient safety.