Forgot password

Not a Member?
JOIN TODAY

HIV and Enteropathy
Advertisement
HLA-B*5701 Screening for Patients Infected With HIV

What is HLA-B*5701 screening?

What are the clinical studies that demonstrated the importance of HLA-B*5701 screening?

Why is it important to determine HLA-B*5701 status in your patients before initiating antiretroviral treatment?

What is the Important Safety Information about hypersensitivity reactions to abacavir?


What is HLA-B*5701 screening?

HLA-B*5701 screening identifies patients with a high risk of a serious and sometimes fatal hypersensitivity reaction (HSR) to abacavir and abacavir-containing products. Abacavir (ABC) is a nucleoside reverse transcriptase inhibitor of HIV reverse transcriptase for use as part of multi-drug antiretroviral regimens for treatment of HIV-1 infection. Serious and sometimes fatal HSRs have been associated with ABC and ABC-containing products. Studies were undertaken to determine if there was a genetic link to HSR. Once this link was confirmed, research efforts led to the successful development of a genetic screening test which is available globally in primary HIV clinical practice to help predict and significantly reduce the risk of this potentially life-threatening drug reaction.

HLA-B*5701–negative patients may develop a hypersensitivity reaction to ABC; however, this occurs significantly less frequently than in HLA-B*5701–positive patients.

In 2001, 2 research groups working independently identified the association between the HLA-B*5701 allele and ABC HSR. Following further pharmacogenetic research, the first commercially available HLA-B*5701 screening assay became available to US clinicians in 2004. In 2006, 2 clinical studies demonstrated the clinical utility of prospective HLA-B*5701 screening to reduce ABC HSR and the generalizability of HLA-B*5701 screening across racial populations. Since then, new laboratory techniques have produced cost-effective screening methods and an international quality assurance program currently exists to ensure the accurate and consistent analytic validity of the tests.

Please see additional Important Safety Information about hypersensitivity reactions to abacavir.


What are the clinical studies that demonstrated the importance of HLA-B*5701 screening?

Before the availability of HLA-B*5701 screening, HSR to ABC was reported in approximately 8% of 2,670 subjects (n=206) in 9 clinical trials (range: 2%-9%).1 After HLA-B*5701 screening became available, it helped to significantly reduce the risk of an ABC HSR in patients who were most susceptible. The importance of HLA-B*5701 screening has been confirmed by various clinical studies including PREDICT-1,2 SHAPE,3 and ARIES.4

PREDICT-1 was a prospective, randomized, double-blind study involving 1956 patients with HIV (predominantly white population) from 19 countries who had not previously received ABC.2 The study was designed to determine if screening for HLA-B*5701 before ABC treatment could help reduce the incidence of ABC HSRs. Results showed that 3.4% of prospectively screened patients had a clinically suspected HSR. However, the results showed no immunologically confirmed ABC HSRs after prospective HLA-B*5701 screening (0% in the prospective screening group vs 2.7% in the control group, P<0.001). Immunologic confirmation was done through skin-patch testing. It is important to note that skin-patch testing was used as a research tool in this study and should not be used to aid in the clinical diagnosis of ABC hypersensitivity. PREDICT-1 established the importance of this one-time test to help reduce the risk of HSRs to ABC.2

SHAPE, a retrospective case-control study, assessed the sensitivity of HLA-B*5701 as a marker in black and white patients in the United States. SHAPE confirmed the importance of the HLA-B*5701 screening test for identifying patients at high risk of developing HSR. The study concluded that the presence of HLA-B*5701 is significantly associated with ABC HSRs, regardless of race and case definition of ABC HSR.3

ARIES, a multicenter trial to demonstrate the safety and efficacy of an ABC-containing regimen, was the first study to utilize prospective HLA-B*5701 screening to exclude patients with the HLA-B*5701 allele. HLA-B*5701 screening resulted in suspected HSR to ABC being reported in 0.8% (4/515) of the HLA-B*5701–negative patients, and subsequent skin-patch testing, used as a research tool in this study, was negative in all 4 of these cases.4

Importantly, a key reason for prospective screening is to enhance patient safety by limiting exposure to ABC in those who are likely to develop HSR to ABC. Additionally, after HLA-B*5701 is determined and recorded in a patient's chart, it serves as a point of reference when initiating or reinitiating ABC therapy at that time or in the future. Knowing a patient's HLA-B*5701 status early on can help healthcare professionals in their treatment decisions, because the patient's HLA-B*5701 status will not change.

Prospective screening offers the opportunity to enhance patient safety by identifying patients who may be at high risk of developing ABC HSR. Patients who have the HLA-B*5701 allele should not be prescribed ABC or ABC-containing products. The US Department of Health and Human Services (DHHS) guidelines recommend screening for HLA-B*5701 before starting patients on an ABC-containing regimen to reduce the risk of HSRs.5

Screening is also recommended prior to reinitiation of ABC in patients of unknown HLA-B*5701 status who have previously tolerated ABC. Once the HLA-B*5701 status is known, it will not change during a patient’s lifetime, and knowing this information is important when considering therapy. There may come a point that a patient might need to be switched from their current therapy, and you might be considering ABC. Having the patient’s HLA-B*5701 status readily available can assist in making this determination.

It is important to determine HLA-B*5701 status as early as possible, even at the patient’s first visit, to support immediate and future treatment decisions.

HLA-B*5701 screening should not be used as a substitute for clinical judgment or pharmacovigilance, because a negative HLA-B*5701 result does not absolutely rule out the possibility of some form of ABC HSR.5

HLA-B*5701 testing should never be performed to diagnose an ABC HSR. HLA-B*5701–positive patients should not be prescribed ABC-containing regimens, and the positive HLA-B*5701 screening test result should be recorded as an ABC allergy in the patient’s medical record.5

It is important to discontinue ABC permanently if HSR cannot be ruled out, regardless of the HLA-B*5701 screening test result.

Please see additional Important Safety Information about hypersensitivity reactions to abacavir.

Why is it important to determine HLA-B*5701 status in your patients before initiating antiretroviral treatment?
HLA-B*5701 screening helps physicians individualize their patients’ treatment plans to significantly reduce the risk of HSRs to ABC or ABC-containing products.6 Screening is a one-time test that can be performed as part of routine baseline assessments done at the initial consultation. Importantly, once screening status is known and recorded in the patient's medical record, healthcare professionals can use this information in deciding if a patient is an appropriate candidate for ABC therapy. After these results become part of the patient’s permanent medical record, healthcare professionals can use this and other patient information to make the appropriate treatment decisions.



Highlights of Important Safety Information About Hypersensitivity Reactions to Abacavir

  • Serious and sometimes fatal hypersensitivity reactions have been associated with abacavir-containing products
  • Hypersensitivity to abacavir is a multi-organ clinical syndrome usually characterized by a sign or symptom in 2 or more of the following groups: fever, rash, gastrointestinal (including nausea, vomiting, diarrhea or abdominal pain), constitutional (including generalized malaise, fatigue, or achiness) and respiratory (including dyspnea, cough, or pharyngitis)
  • Patients who carry the HLA-B*5701 allele are at high risk for experiencing a hypersensitivity reaction to abacavir
  • Prior to initiating therapy with abacavir, screening for the HLA-B*5701 allele is recommended; screening is also recommended prior to reinitiation of abacavir in patients of unknown HLA-B*5701 status who have previously tolerated abacavir
  • HLA-B*5701−negative patients may develop a suspected hypersensitivity reaction to abacavir; however, this occurs significantly less frequently than in HLA-B*5701−positive patients
  • Discontinue any abacavir-containing product as soon as a hypersensitivity reaction is suspected. Regardless of HLA-B*5701 status, permanently discontinue abacavir-containing product if hypersensitivity cannot be ruled out, even when other diagnoses are possible
  • Following a hypersensitivity reaction to abacavir, NEVER restart any abacavir-containing product because more severe symptoms can occur within hours and may include life-threatening hypotension and death

 

Indication and Usage

  • EPZICOM (abacavir sulfate 600 mg + lamivudine 300 mg), in combination with other antiretroviral agents, is indicated for the treatment of HIV-1 infection. EPZICOM is one of multiple products containing abacavir
  • Before starting EPZICOM, review medical history for prior exposure to any abacavir-containing product in order to avoid reintroduction in a patient with a history of hypersensitivity to abacavir
  • In one controlled study, more patients taking abacavir 600 mg once daily had severe hypersensitivity reactions compared to patients taking abacavir 300 mg twice daily
  • As part of a triple-drug regimen, EPZICOM is recommended for use with ART agents from different pharmacological classes and not with other NRTIs


Other abacavir-containing products include TRIZIVIR (abacavir/zidovudine/lamivudine) and ZIAGEN (abacavir). These products are also approved for the treatment of HIV-1 infection in combination with other antiretroviral agents.

Click here to view the full Prescribing Information, including Boxed Warning for EPZICOM®.
Click here to view the full Prescribing Information, including Boxed Warning for TRIZIVIR®.
Click here to view the full Prescribing Information, including Boxed Warning for ZIAGEN®.

Click here to learn more about ViiV Healthcare Group of Companies.


References: 1. EPZICOM [prescribing information]. Research Triangle Park, NC: ViiV
Healthcare Group of Companies; 2012.  2. Mallal S, Phillips E, Carosi G, et al; for the
PREDICT-1 Study Team. HLA-B*5701 screening for hypersensitivity to abacavir. N Engl J
Med
. 2008;358(6):568-579. 3. Saag M, Balu R, Phillips E, et al; for the Study of
Hypersensitivity to Abacavir and Pharmacogenetic Evaluation Study Team. High
sensitivity of human leukocyte antigen–B*5701 as a marker for immunologically
confirmed abacavir hypersensitivity in white and black patients. Clin Infect Dis.
2008;46(1):1111-1118. 4. Squires KE, Young B, DeJesus E, et al; for the ARIES Study
Team. Safety and efficacy of a 36-week induction regimen of abacavir/lamivudine and
ritonavir-boosted atazanavir in HIV-infected patients. HIV Clin Trials. 2010;11(2):69-79.
5.
Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use
of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health
and Human Services.http://www.aidsinfo.nih.gov/contentfiles/lvguidelines/
adultandadolescentgl.pdf. Accessed January 24, 2013. 6. Lalonde RG, Thomas R, Rachlis
A, et al. Successful implementation of a national HLA-B*5701 genetic testing service in
Canada. Tissue Antigens. 2009;75:12-18.
 



 

 

Bookmark and Share