A randomized non-inferiority trial comparing the safety and efficacy of fosamprenavir/ritonavir and lopinavir/ritonavir, each in combination with EPZICOM
- Background: Using EPZICOM as a backbone in each arm, fosamprenavir/ritonavir had never been directly compared with lopinavir/ritonavir
- Methods: 878 antiretroviral-naïve patients were randomized to EPZICOM once daily plus either fosamprenavir/ritonavir 700 mg/100 mg twice daily (n=434) or lopinavir/ritonavir 400 mg/100 mg twice daily (n=444). The primary endpoint was the percentage of patients with HIV-1 RNA <400 copies/mL at 48 weeks. Safety and tolerability were assessed, including discontinuations due to adverse events
- Results: Similar efficacy outcomes were observed between both groups at 48 weeks. Of the patients tested, 73% (315/434) in the fosamprenavir/ritonavir + EPZICOM and 71% (317/444) in the group receiving the lopinavir/ritonavir + EPZICOM achieved HIV-1 RNA <400 copies/mL at 48 weeks. The results were similar with HIV-1 RNA <50 copies/mL at 48 weeks (66% and 65%, respectively) as shown below. Increases in CD4+ cell counts were also similar between groups
Both groups also showed similar outcomes in safety and tolerability. Frequency of discontinuations due to adverse events was low in both groups [fosamprenavir/ritonavir + EPZICOM: 12% (53/424); lopinavir/ritonavir + EPZICOM: 10% (43/444)]. The most frequent grade 2-4 AEs were diarrhea (12%), nausea (6%), and hypersensitivity to abacavir (5%).
- Conclusions: Findings from the KLEAN study suggest that EPZICOM, combined with either fosamprenavir/ritonavir or lopinavir/ritonavir, is an effective choice in treatment-naïve patients
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%)
