BUENOS AIRES, ARGENTINA -- July 9, 2001 -- Final one-year results of the international COMBINE study show that an anti-HIV (human immunodeficiency virus) treatment regimen of Viramune® (nevirapine) plus Combivir™ (3TC/ZDV)* demonstrated comparable efficacy, when compared to a regimen of the protease inhibitor nelfinavir* plus Combivir, in reducing HIV below detectable limits.
The findings were presented at the first International AIDS Society Conference on HIV Pathogenesis and Treatment.
"After one year of treatment, a similar percentage of patients taking Viramune plus Combivir had undetectable levels of HIV (less than 20 copies/mL) in their blood than those taking nelfinavir plus Combivir," said Daniel Podzamczer, MD, lead investigator, of the Hospital Princeps d'Espanya in Barcelona, Spain. "This study adds to the growing collection of evidence which support the use of a protease-inhibitor-sparing treatment combination."
Patients receiving the Viramune plus Combivir regimen took a total of four tablets daily during the study, while those receiving the nelfinavir plus Combivir regimen were required to take a total of twelve tablets per day.
Viramune is a non-nucleoside reverse transcriptase inhibitor (NNRTI) indicated for use in combination with other antiretroviral agents for the treatment of HIV-1 infection. This indication is based on analysis of changes in surrogate end-points, such as viral load or CD4+ count. At present there are no published results from controlled clinical trials evaluating the effect of Viramune in combination with other antiretrovirals on the clinical progression of HIV-1 infection. Resistant virus emerges rapidly when it is administered alone.
COMBINE is a randomized, open-label, multicenter trial of 142 patients in 12 hospitals in Spain and Argentina. The study compared the efficacy and safety of Viramune plus Combivir to nelfinavir plus Combivir in patients who have not previously been treated with antiretroviral therapy.
In a missing equals failure intent-to-treat (ITT) analysis at 12 months, 75 percent of patients in the Viramune arm and 60 percent in the nelfinavir arm were below the limit of detection (<200 copies/mL); 65 percent and 50 percent, respectively, were below 20 copies/mL. In an on-treatment (OT) analysis, 92 percent in the Viramune arm versus 81 percent in the nelfinavir arm had undetectable levels of HIV (<200 copies/mL) and 80 percent and 71 percent were below 20 copies/mL.
Baseline characteristics of patients in both treatment groups were similar. Mean CD4+ count was 359 cells/mm3. Mean HIV-RNA was 5.15 log10. Researchers reported no differences when comparing efficacy rates in a subgroup of patients with very high baseline levels of virus (>100,000 copies/mL). In this high viral load subgroup, an ITT analysis found 76.1 percent of patients in the Viramune arm and 53.8 percent of patients in the nelfinavir arm were below the limit of detection (<200 copies/mL).
No differences were observed in the gain of CD4+ cell counts; at 12 months, each group showed an increase of approximately 160 cells/mm3. A detailed immune restoration sub-study showing similar results with both regimens will be presented separately as a poster during the Conference.
The regimens were generally well tolerated by patients, although some serious adverse events were reported. A total of seven patients discontinued ZDV and switched to d4T due to anemia or neutropenia (an abnormal drop in white blood cells). Additionally, 12 out of 72 patients stopped taking Viramune due to adverse events, which were hepatitis or rash. Fourteen of 70 patients stopped taking nelfinavir because of adverse events, mainly gastrointestinal symptoms.
The most clinically important adverse events associated with Viramune are rash (16 percent) and hepatic events. Other commonly reported events include fever, nausea and headache. Cases of hypersensitivity reactions have been observed. Severe and life-threatening skin reactions and hepatotoxicity, including fatal cases of each, have occurred in patients treated with Viramune. Some events have occurred after short-term exposure. The first 12 weeks of therapy with Viramune are a critical period during which it is essential that patients be intensively monitored. Viramune should not be restarted following severe hepatic, skin or hypersensitivity reactions.
The dose of Viramune for adults is one 200 mg tablet daily for the first 14 days (this lead-in period should be used because it has been found to lessen the frequency of rash), followed by one 200 mg tablet twice daily. Resistant virus emerges rapidly and uniformly when Viramune is administered alone. For the treatment of HIV-1 infection, Viramune should always be administered in combination with other antiretroviral agents.
*Antiretroviral drugs mentioned in this release: Combivir™ (3TC 150 mg/ZDV 300 mg), Glaxo SmithKline; nelfinavir (Viracept®), Agouron Pharmaceuticals Inc.; d4T (Zerit®), (stavudine) Bristol-Myers Squibb Co.
SOURCE: Boehringer Ingelheim Pharmaceuticals, Inc.
Related Link: Boehringer Ingelheim Pharmaceuticals, Inc.
