A retrospective, case-control evaluation of the sensitivity and specificity of the HLA-B*5701 allele for hypersensitivity to abacavir
- Background: Although several small studies have suggested a correlation between the HLA-B*5701 allele and abacavir hypersensitivity in Whites, similar studies needed to be carried out in other racial and ethnic groups to support or refute that link more broadly
- Methods: White and black patients, each with at least two major symptoms of abacavir hypersensitivity, were recruited for
HLA-B*5701 testing and skin patch testing, along with 200 controls. Skin patch testing is a research tool used in this study to determine if a patient has had a previous immune-mediated reaction to abacavir (hypersensitivity)
- Results: All white patients (42/42) with clinically suspected hypersensitivity and a positive skin patch test were also
positive for HLA-B*5701. In the 5 black patients with clinically suspected hypersensitivity and a positive skin patch test, all were HLA-B*5701 positive. Due to the large number of patients with a clinical diagnosis of hypersensitivity that were not confirmed by skin patch testing, sensitivity was low for both Whites (44%) and Blacks (14%). Specificity was high for both groups (Whites 96%, Blacks 99%), as few patients in the control group (without clinically suspected hypersensitivity) were positive for the HLA-B*5701 allele
- Conclusions: SHAPE supports the utility of
HLA-B*5701 testing to screen for abacavir hypersensitivity in both white and black populations. However, the limited representation of Blacks in this study must be taken into account
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%)
