The PREDICT-1 study

Learn more about the test for hypersensitivity

A randomized, double-blind trial to determine the clinical utility of HLA-B5701* screening for abacavir hypersensitivity (ABC HSR)

Background: Small studies have indicated a correlation between abacavir hypersensitivity and the presence of the HLA-B*5701 allele. This trial evaluated the effects of prospective screening for HLA-B*5701 on the rate of hypersensitivity
Methods: 1,956 mostly white, abacavir-naïve patients with HIV-1 infection and unknown HLA-B*5701 status were randomized in a 1:1 ratio to receive either prospective or retrospective HLA-B*5701 screening. Prospectively screened patients who were HLA-B*5701 positive were removed from the study, and the remaining subjects in both arms received 6 weeks of abacavir-containing therapy. Skin patch testing is a research tool used in this study to determine if a patient with a clinical diagnosis of hypersensitivity also had an immune-mediated reaction to abacavir
Results: The rate of clinically suspected hypersensitivity was significantly less in the prospectively screened arm (3.4%) than in the control arm (7.8%) (P<0.0001). When coupled with skin patch testing, the rate of clinically suspected hypersensitivity with a positive skin patch test was zero in the prospectively screened arm and 2.7% in the control arm (P<0.0001).

Conclusions: Prospective HLA-B*5701 testing was effective in identifying patients who had a higher risk of hypersensitivity to abacavir, and screening out patients positive for HLA-B*5701 can reduce the overall incidence of HSR

Important Points to Keep in Mind:

HLA-B*5701 screening should be performed in patients without prior abacavir exposure.

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

HLA-B*5701 testing should never be performed to diagnose an abacavir hypersensitivity reaction.

HLA-B*5701 testing should never be performed diagnostically to support a decision to rechallenge with abacavir.

Results from HLA-B*5701 testing to assess risk for abacavir HSR should never substitute for appropriate clinical vigilance and patient management in individuals undergoing treatment with abacavir-containing treatments.

Results from pharmacogenetic testing, as with any laboratory test, should be evaluated as part of the overall clinical diagnosis and management of a patient.

Indication and Usage

EPZICOM, 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

It is not recommended that EPZICOM be used as a component of a triple-nucleoside regimen

Important Safety Information

EPZICOM contains abacavir sulfate, which has been associated with serious and sometimes fatal hypersensitivity reactions. Hypersensitivity to abacavir is a multi-organ clinical syndrome usually characterized by a sign or symptom in 2 or more of the following groups: (1) fever, (2) rash, (3) gastrointestinal (including nausea, vomiting, diarrhea, or abdominal pain), (4) constitutional (including generalized malaise, fatigue, or achiness), and (5) respiratory (including dyspnea, cough, or pharyngitis). Discontinue EPZICOM as soon as a hypersensitivity reaction is suspected. Permanently discontinue EPZICOM if hypersensitivity cannot be ruled out, even when other diagnoses are possible
Following a hypersensitivity reaction to abacavir, NEVER restart EPZICOM or any other abacavir-containing product because more severe symptoms can occur within hours and may include life-threatening hypotension and death
Reintroduction of EPZICOM or any other abacavir-containing product, even in patients who have no identified history or unrecognized symptoms of hypersensitivity to abacavir therapy, can result in serious or fatal hypersensitivity reactions. Such reactions can occur within hours
Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues alone or in combination, including abacavir, lamivudine, and other antiretrovirals
EPZICOM Tablets are contraindicated in patients with hepatic impairment
Severe acute exacerbations of hepatitis B have been reported in patients who are coinfected with hepatitis B virus (HBV) and HIV and have discontinued lamivudine, which is one component of EPZICOM. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who discontinue EPZICOM and are coinfected with HIV and HBV. If appropriate, initiation of anti-hepatitis B therapy may be warranted
Hepatic decompensation (some fatal) has occurred in HIV/HCV coinfected patients receiving combination antiretroviral therapy for HIV and interferon with or without ribavirin. Patients receiving interferon with or without ribavirin and EPZICOM should be closely monitored for treatment-associated toxicities, especially hepatic decompensation. Discontinuation of EPZICOM should be considered as medically appropriate
Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy, including EPZICOM. During the initial phase of combination antiretroviral treatment, patients whose immune systems respond may develop an inflammatory response to indolent or residual opportunistic infections (such as Mycobacterium avium infection, cytomegalovirus, Pneumocystis jirovecii pneumonia [PCP], or tuberculosis), which may necessitate further evaluation and treatment
Redistribution/accumulation of body fat has been observed in patients receiving antiretroviral therapy. The causal relationship, mechanism, and long-term consequences of these events are currently unknown
In one study of therapy-naïve patients (CNA 30021), the most common adverse events (grade 2-4) reported with abacavir and lamivudine dosed once daily were hypersensitivity (9%), insomnia (7%), depression (7%), headache/migraine (7%), fatigue (6%), dizziness (6%), nausea (5%), diarrhea (5%), rash (5%), pyrexia (5%), abdominal pain (4%), abnormal dreams (4%), and anxiety (3%)

A randomized, double-blind trial to determine the clinical utility of HLA-B*5701 screening for abacavir hypersensitivity (ABC HSR)

A randomized, double-blind trial to determine the clinical utility of HLA-B5701* screening for abacavir hypersensitivity (ABC HSR)