Long-term Results of First Head-to-Head Trial of a Triple Cocktail Regimen Involving the Three Classes of Antiretrovirals

INGELHEIM (ots-PRNewswire) - Data on VIRAMUNE(R) in Different Treatment Settings Presented at ICAAC Meeting Today researchers unveil the eagerly awaited 48-week results of the international, multicenter Atlantic trial -- the first head-to-head comparison of agents in the three currently available classes of HIV/AIDS drugs in a triple-drug cocktail regimen. These preliminary results, and other clinical data supporting the use of the non-nucleoside reverse transcriptase inhibitor (NNRTI), VIRAMUNE(R) (nevirapine), were presented at the 39th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) meeting in San Francisco/USA. The 48-week Atlantic data presented at a "latebreaker" session today show that patients on the VIRAMUNE regimen achieved HIV reductions that were equivalent to patients on the protease inhibitor (PI) and the nucleoside analogue regimens. The primary Atlantic study objective is to assess which of three treatment regimens results in the greatest reduction of the serum plasma HIV RNA to undetectable levels (<50 copies/ml) in previously untreated patients. The treatment combinations consist of a background of d4T and ddI (nucleoside analogues) combined with either once-daily VIRAMUNE, three-times-daily indinavir (protease inhibitor) or twice-daily 3TC (nucleoside analogue).* These three drugs each have a different mechanism of action. "These results confirm our 24-week findings that a tolerable, PI-sparing regimen, such as the VIRAMUNE regimen, can achieve and sustain significant viral reduction," said lead Atlantic investigator, Professor Joep Lange of the National AIDS Therapy Evaluation Centre (NATEC), University of Amsterdam. Using an 'intent-to-treat analysis', which accounts for all patients, including those who stopped treatment before the end of the study, Atlantic researchers found the percentage of patients with undetectable HIV-1 RNA (<50 copies/ml) at 48 weeks was 51% in the VIRAMUNE arm, 57% in the indinavir (PI) arm and 49% in the 3TC (nucleoside analogue) arm. The percentage of patients with HIV-1 RNA <500 copies/ml was 91% in the VIRAMUNE arm, 95% in the indinavir arm and 90% in the 3TC arm. In the 'as-treated analysis', which accounts for patients who did not stop therapy due to toxicity or loss to follow-up, the percentage with undetectable HIV-1 RNA (<50 copies/ml) was 82% in the VIRAMUNE arm, 90% in the indinavir arm and 78% in the 3TC arm. Researchers also presented a sub-analysis of patients with high levels of the virus in their blood (> 51,286 copies/ml at the start of the study) as compared to patients with a lower viral load. In this sub analysis, the VIRAMUNE regimen also was as effective at reducing levels of HIV as the protease inhibitor regimen in these patients, with 50% and 55% of patients reaching undetectable levels of HIV, respectively. In this same sub analysis more patients in the 3TC+d4T+ddI group had HIV-1 RNA >50 copies/ml compared to the other groups after 48 weeks of therapy. Safety data for the 48-week period indicated that the therapies were safe and generally well tolerated. Adverse event rates were not significantly different for each treatment group. Researchers plan to follow patients in the study for more than 144 weeks. The virologic effects of the three regimens on HIV replication in lymphoid tissue, and the occurrence of lipodystrophy will also be evaluated. Additionally, a follow-up salvage study is being initiated. MAINTAVIR Study In a "substitution" trial called MAINTAVIR, Professor Francois Raffi of the Centre Hospitalier Regional et Universitaire de Nantes, France reports that switching to an NNRTI-based regimen from a protease inhibitor-based regimen simplified patients' treatment regimens and reduced the symptoms of lipodystropy while maintaining HIV suppression. "Our goal is to find simple treatment regimens that are well- tolerated, potent and durable," said Dr. Raffi. "Switching patients from a protease inhibitor to a non-nucleoside such as VIRAMUNE achieved these goals in the short-term. Our findings show that the majority of patients maintain undetectable levels of HIV." Patients in the MAINTAVIR study switched from their protease- containing regimens to an NNRTI, either VIRAMUNE (47 patients) or efavirenz (6 patients). After switching to an NNRTI, 87% (46/53) of patients continued to have undetectable virus (<80 copies/ml) for a mean follow-up of 21 weeks. Reasons for switching include adherence problems, digestive symptoms and lipodystrophy, or in most patients, the wish to simplify the regimen. All participants had received at least one year of protease inhibitor therapy and no prior NNRTI therapy. All patients had maintained levels of HIV below the limit of detection (<400 copies/ml) for at least the previous six months. BEGIN Study The BEGIN Study explores the efficacy and tolerability of switching from a protease inhibitor to an NNRTI (nevirapine or efavirenz) in combination with two nucleoside analogues. Preliminary results show that an NNRTI-based treatment regimen maintains viral suppression and offers a more tolerable alternative to PI-based therapies. Vicente Munoz, MD, Jose L. Casado, MD, et al in Madrid, Spain offered 116 patients the option to switch to VIRAMUNE (73) or efavirenz (43) because of intolerance to protease inhibitors. Of the 67% of patients with undetectable levels of HIV at baseline (<200 copies/ml), 83% of them remained below 50 copies/ml after 12 weeks on the NNRTI-based therapy by intent-to-treat, and 96% of them in an "as treated" analysis. Of the patients that had HIV levels >200 copies/ml on protease inhibitor therapy, 54% achieved undetectable levels of HIV and an additional 31% achieved a significant reduction (>1.0 log10) in levels of HIV after 12 weeks on the NNRTI-based therapy. Triglycerides and cholesterol both showed a significant decrease in those patients on an NNRTI. Adequate adherence (>95%) to the prescribed regimen increased from 71% with PI-based therapy to 91% with NNRTI-based therapy (p<0.01). Twenty-eight percent of patients reported adverse events, and 14% had to discontinue NNRTI treatment. The most common adverse events were different for nevirapine or efavirenz, with 23% of patients with efavirenz reporting any grade of CNS disturbance and 8% of patients with nevirapine suffering rash. VIRAMUNE VIRAMUNE is 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. At present, there are no results from controlled clinical trials evaluating the effect of VIRAMUNE in combination with other antiretroviral agents on the clinical progression of HIV-1 infection, such as the incidence of opportunistic infections or survival. VIRAMUNE should always be administered in combination with at least one additional antiretroviral agent. VIRAMUNE is generally well tolerated. In clinical trials the most commonly reported adverse events associated with VIRAMUNE use are rash, fever, nausea, headache and abnormal liver function tests. Severe and life-threatening skin reactions and hepatotoxicity, including fatal cases of each, have occurred in patients treated with VIRAMUNE. VIRAMUNE is a product of original research done at Boehringer Ingelheim Pharmaceuticals, Inc., a member of the Boehringer Ingelheim group of companies. VIRAMUNE is marketed world-wide by Boehringer Ingelheim and in the United States by Roxane Laboratories, also a member of the Boehringer Ingelheim group of companies. Boehringer Ingelheim corporation, headquartered in Ingelheim (Germany) is one of the 20 leading pharmaceutical corporations in the world. It reported revenues exceeding DM 8.7 million in 1998. The corporation has more than 140 affiliated companies and it conducts business on every continent. Its product range is focused on human pharmaceuticals -- hospital, prescription and self-medication -- as well as animal health. The group of companies has substantial research and development, production, and distribution facilities around the globe. In 1998 the Boehringer Ingelheim corporation spent DM 1.6 billion on R&D, equivalent to 18 % of total sales. * Antiretroviral drugs mentioned in release -- VIRAMUNE(R) (nevirapine, NVP), Boehringer Ingelheim/Roxane Laboratories -- d4T (Zerit(R), stavudine), Bristol-Myers Squibb -- ddI (Videx(R), didanosine), Bristol-Myers Squibb -- indinavir (Crixivan(R)), Merck & Co. -- 3TC (Epivir(R), lamivudine), Glaxo Wellcome Inc. -- efavirenz (Sustiva(R)) Dupont Pharmaceutical ots Original Text Service: Boehringer Ingelheim GmbH Internet: http://www.newsaktuell.de Contact: Judith von Gordon, Corporate Public Relations Division of Boehringer Ingelheim GmbH, +49-6132- 773582 or fax, +49-6132-776601; or Maureen Byrne or Denise Connolly, both of GCI Healthcare, 212-886-3312 or 212-886-3117, or 212-886-3291 Subscribers please note that material bearing the slug "PROTEXT" is not part of CTK's news service and is not to be published under the "CTK" slug. Protext is a commercial service providing distribution of press releases from clients, who are identified in the text of Protext reports and who bear full responsibility for their contents. PROTEXT