PRNewswire - October 31, 2004

-- The quad NRTI regimen of TRIZIVIR + tenofovir shows efficacy in treatment-naive patients; may preserve future treatment options.

-- Patients who achieved viral suppression on an initial ART regimen retain viral suppression when switched to a simplified regimen of TRIZIVIR alone, or COMBIVIR + nevirapine.

WASHINGTON, Oct. 31 /PRNewswire/ -- GlaxoSmithKline (GSK) today announced that new information from ongoing clinical trials investigating varied clinical applications for TRIZIVIR(R) (abacavir sulfate, lamivudine, and zidovudine) were presented at the 44th annual meeting of the Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC).

TRIZIVIR, the first tablet to combine three medications for HIV, is a fixed-dose-combination tablet containing three nucleoside reverse transcriptase inhibitors (NRTIs).

"These data help demonstrate the versatility of TRIZIVIR as a treatment for HIV in different clinical situations, and illustrate GSK's ongoing commitment to simplify HIV treatment regimens for many patients," said Doug Manion, M.D., vice president for HIV Clinical Research for the Infectious Diseases Medicines Development Center (MDC) at GSK.

TIMS - Quad Therapy TRIZIVIR + Tenofovir, Compared with Triple Therapy COMBIVIR + Efavirenz

In an open-label study reported at ICAAC, 114 treatment-naove patients were randomized to receive the single-class quad NRTI regimen of TRIZIVIR plus tenofovir disoproxil fumarate (TDF) or a regimen of a dual-class triple regimen of two NRTIs (COMBIVIR) and the nonnucleoside reverse transcriptase inhibitor (NNRTI) efavirenz (EFV). These data were reported by Graeme Moyle, M.D., of Chelsea and Westminster Hospital, London.

At week 48 intent-to-treat analysis, 40 of 57 patients (70 percent) on the regimen containing TRIZIVIR plus TDF and 39 of 57 patients (68 percent) on the regimen containing COMBIVIR plus EFV had undetectable viral loads (VL) <50 copies/mL. Mean baseline (BL) VL was 5.13log(10) and mean CD4 cell count was 153 cells/mm(3) in the group randomized to take TRIZIVIR plus TDF, and 5.26log(10) and 193 cells/mm(3), respectively, in the group taking COMBIVIR plus EFV. In intent-to-treat analysis, results are included for all patients randomized to a study, regardless of whether they actually completed the study protocol and patients with missing data are considered treatment failures.

ESS30005 (ZIP) - Regimens for Patients with Early Virologic Failure In a second study presented at ICAAC, 51 patients experiencing early virologic failure on a regimen of RETROVIR(R) (zidovudine, ZDV) or stavudine (d4T) plus EPIVIR(R) (lamivudine, 3TC), combined with either a PI or NNRTI were switched to open-label TRIZIVIR twice daily (BID) plus TDF once daily (QD). In a planned 24 week interim analysis, proportions with HIV RNA <400 c/mL were 75 percent (ITT missing = failure). HIV RNA <50 c/mL was achieved by 65 percent (ITT missing = failure) at week 24. No subject experienced confirmed virologic failure through week 24. At BL, media VL was 1,972 copies/mL and median CD4 was 436 cells/mm(3).

"Patients with early virologic failure on an NNRTI-based or PI-based regimen may be appropriate candidates for a quad regimen containing TRIZIVIR," said Allan Rodriguez, M.D., associate professor of medicine, division of infectious diseases, University of Miami School of Medicine.

In addition to TRIZIVIR and COMBIVIR, GSK markets another fixed-dose- combination-tablet containing two antiretroviral medications: EPZICOM(TM) (abacavir sulfate and lamivudine), which is a combination of EPIVIR plus ZIAGEN(R) (abacavir sulfate).

Product Information

HIV medicines do not cure HIV infection/AIDS or prevent passing HIV to others.

TRIZIVIR was the first and remains the only HIV drug therapy in the U.S. that combines three nucleoside reverse transcriptase inhibitors (NRTIs) into one tablet. TRIZIVIR is indicated alone or in combination with other antiretroviral agents for the treatment of HIV-1 infection. The indication for TRIZIVIR is based on two controlled trials with abacavir of 16 and 48 weeks in duration that evaluated suppression of HIV RNA and changes in CD4 cell count.

At present, there are no results from controlled trials evaluating the effect of abacavir on clinical progression of HIV. There are limited data on the use of this triple-combination regimen in patients with higher viral load levels (>100,000 copies/mL) at baseline. The daily dosing recommendation for TRIZIVIR is one tablet taken twice daily, with or without food or water. TRIZIVIR is intended only for patients whose regimen would otherwise include its three components. Because it is a fixed-dose tablet, TRIZIVIR should not be prescribed for adults who weigh less than 40 kg, or other patients requiring dosage adjustment.

The most serious adverse event associated with abacavir (a medicine in TRIZIVIR, ZIAGEN and EPZICOM) is a hypersensitivity reaction that can be life threatening and has been fatal in some cases. The hypersensitivity reaction is characterized by fever, rash, gastrointestinal symptoms, such as nausea, vomiting, diarrhea or abdominal pain, symptoms such as generalized malaise, fatigue or achiness, and/or respiratory symptoms such as dyspnea, pharyngitis, or cough. Symptoms of this reaction usually occur within the first six weeks of treatment although the reaction can occur at any time.

To avoid a delay in diagnosis and minimize the risk of a life-threatening hypersensitivity reaction, TRIZIVIR, ZIAGEN or EPZICOM should be permanently discontinued if hypersensitivity cannot be ruled out, even when other diagnoses are possible (e.g., acute onset respiratory disease, gastroenteritis, or reactions to other medication). Rechallenge is contraindicated after a diagnosis of hypersensitivity. The symptoms of this reaction get progressively worse with continued treatment with abacavir (TRIZIVIR, ZIAGEN or EPZICOM), but generally resolve following permanent discontinuation of TRIZIVIR, ZIAGEN or EPZICOM. Patients experiencing these symptoms should stop taking TRIZIVIR, ZIAGEN or EPZICOM and contact a physician immediately. Patients experiencing this reaction must not take TRIZIVIR, ZIAGEN or EPZICOM again as restarting the drug after a hypersensitivity reaction has resulted in cases of life-threatening and fatal reactions. When therapy with TRIZIVIR, ZIAGEN and EPZICOM has been discontinued and reinitiation of therapy is under consideration, the reason for discontinuation should be evaluated to ensure that the patient did not have a hypersensitivity reaction. A Medication Guide and Warning Card for TRIZIVIR, ZIAGEN and EPZICOM must be provided by the pharmacists to the patient with each new and refill prescription in order to provide further information to the patient on this drug.

COMBIVIR is a combination tablet containing EPIVIR(R) (lamivudine) and RETROVIR(R) (zidovudine). COMBIVIR in combination with other antiretroviral agents is indicated for the treatment of HIV infection. Most frequent adverse events with COMBIVIR are headache (35 percent), nausea (33 percent), malaise/fatigue (27 percent), and nasal signs and symptoms (20 percent).

EPIVIR in combination with other antiretroviral agents is indicated for the treatment of HIV infection. EPIVIR should be used with caution in pediatric patients with a history of prior antiretroviral nucleoside exposure, a history of pancreatitis, or other significant risk factors for the development of pancreatitis. Patients with HIV or coinfected with HIV and hepatitis B should only receive the recommended HIV dosage of EPIVIR (300 mg/day) and not EPIVIR-HBV(R) (100 mg/day). EPIVIR has not been adequately studied for treatment of chronic hepatitis B in coinfected patients. Some patients infected with both HIV and hepatitis B virus (HBV) have worsening of hepatitis after stopping EPIVIR. Patients should discuss any change in treatment with their doctor. Coinfected patients should be closely monitored by their doctor for at least several months after stopping treatment RETROVIR in combination with other antiretroviral agents is indicated for the treatment of HIV infection. RETROVIR is also indicated for the prevention of maternal-fetal HIV transmission as part of a regimen that includes oral RETROVIR beginning between 14 and 34 weeks of gestation, intravenous RETROVIR during labor, and administration of RETROVIR Syrup to the neonate after birth.

RETROVIR has been associated with hematologic toxicity including neutropenia and severe anemia particularly in patients with advanced HIV disease. Prolonged use of RETROVIR has been associated with symptomatic myopathy. 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, zidovudine, lamivudine and other antiretrovirals.

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.

The most common adverse events associated with the use of Trizivir greater than or equal to 5 percent Grades 1-4 (Grades 3-4) were nausea 60 percent (3 percent), malaise and fatigue 44 percent (2 percent), nausea and vomiting 30 percent (2 percent), headache 28 percent (<1 percent), diarrhea 26 percent (<1 percent), fever and/or chills 20 percent (3 percent) , loss of appetite/anorexia 15 percent (0 percent), and insomnia and other sleep disorders 13 percent (0 percent).

Recombinant laboratory strains of HIV-1 (HXB2) containing multiple reverse transcriptase mutations conferring abacavir resistance exhibited cross- resistance to lamivudine, didanosine, and zalcitabine in vitro.

GlaxoSmithKline is one of the world's leading research-based pharmaceutical and healthcare companies and an industry leader in HIV research and therapies. The company is engaged in basic research programs designed to investigate new targets to treat HIV.

For full prescribing information please go to http://www.treathiv.com .

SOURCE GlaxoSmithKline

Web Site: http://www.treathiv.com

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