Clinical data

A number of studies have been performed to investigate whether HLA-B*5701 screening is an effective and feasible procedure to reduce the incidence of abacavir HSR.

  • PREDICT-1 study {^1}

    The PREDICT-1 study (CNA106030) was a pivotal, double blinded, randomised clinical trial to establish the effectiveness of the HLA-B*5701 allele as a predictive marker for abacavir (ABC) hypersensitivity reaction (HSR).

    1,956 ABC naive subjects randomised 1:1 in a double blinded fashion to:

    • Arm A) Retrospective HLA-B*5701 testing after starting ABC therapy (Controls)
    • Arm B) Prospective HLA-B*5701 screening; positive patients excluded pre- ABC therapy

    Retrospective epicutaneous patch testing (EPT) was carried out in all cases of clinically suspected ABC HSR.

    Incidence of Clinically Suspected Abacavir Hypersensitivity

    a Intention-to-treat evaluable population.
    b Prospective screen versus control adjusted for actual strata of race, ART status, introduction of NNRTI, and concurrent PI use.

    Incidence of Immunologically Confirmed Abacavir Hypersensitivity

    a Intention-to-treat evaluable population.
    b Prospective screen versus control adjusted for actual strata of race, ART status, introduction of NNRTI, and concurrent PI use.

    Conclusions

    It was estimated that 48% - 61% of patients with HLA-B*5701 will develop HSR on ABC containing therapy vs. 0% to 4% of patients who do not have the allele.

  • SHAPE study{^2}

    SHAPE (ABC107442) is a retrospective case-control study to estimate the sensitivity and specificity of the HLA-B*5701 allele in self-reported White and Black subjects with and without suspected ABC HSR, using EPT to supplement clinical diagnosis of abacavir hypersensitivity.

    Conclusions

    • 100% sensitivity of HLA-B*5701 in white and black subjects with EPT confirmed ABC HSR
    • Lower sensitivity of HLA-B*5701 screening observed when ABC HSR was defined by clinical diagnosis alone
    • Not all HLA-B*5701 positive subjects had a positive EPT test result
    • Prospective HLA-B*5701 screening may reduce ABC HSR rates in white and black subjects
    • The presence of the HLA-B*5701 allele is associated with increased risk of ABC HSR, regardless of race
  • HLA-B{+}5701 screening data{^3-6}

    A limitation of the PREDICT-1 study was that investigators were blinded to subjects HLA-B*5701 status during the study, which would not be the case in clinical practice.

    Recent marketing authorisation holder (MAH) trials, which prospectively screened for the HLA-B*5701 allele and excluded subjects testing positive, more accurately reflect experience and reporting rates in clinical practice.

    MAH Sponsored Clinical Trials with prospective HLA-B*5701 screening ABC containing treatment group HSR Reporting Rate
    % (n/N)
    ASSERT (CNA109586)3 ABC/3TC + EFV 3.1 (6/192)
    ARIES (EPZ108859)4 ABC/3TC + ATV+ RTV 1 (4/517)
    ASSURE (EPZ113734)5 ABC/3TC + ATV <1 (1/199)
    SINGLE (ING114467)6 ABC/3TC + DTG <1 (1/414)
    Total   1 (12/1322)

    ABC/3TC = KIVEXA; ATV = atazanavir; DTG = dolutegravir; EFV = efavirenz; RTV = ritonavir.