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 DifferentTreatment Settings Presented at ICAAC Meeting Today researchers unveil the eagerly awaited 48-week resultsof the international, multicenter Atlantic trial -- the firsthead-to-head comparison of agents in the three currentlyavailable classes of HIV/AIDS drugs in a triple-drug cocktailregimen. These preliminary results, and other clinical datasupporting the use of the non-nucleoside reverse transcriptaseinhibitor (NNRTI), VIRAMUNE(R) (nevirapine), were presented atthe 39th Interscience Conference on Antimicrobial Agents andChemotherapy (ICAAC) meeting in San Francisco/USA. The 48-week Atlantic data presented at a "latebreaker" sessiontoday show that patients on the VIRAMUNE regimen achieved HIVreductions that were equivalent to patients on the proteaseinhibitor (PI) and the nucleoside analogue regimens. The primary Atlantic study objective is to assess which ofthree treatment regimens results in the greatest reduction of theserum plasma HIV RNA to undetectable levels (<50 copies/ml) inpreviously untreated patients. The treatment combinations consistof a background of d4T and ddI (nucleoside analogues) combinedwith 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 andsustain significant viral reduction," said lead Atlanticinvestigator, Professor Joep Lange of the National AIDS TherapyEvaluation Centre (NATEC), University of Amsterdam. Using an 'intent-to-treat analysis', which accounts for allpatients, including those who stopped treatment before the end ofthe study, Atlantic researchers found the percentage of patientswith 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 the3TC (nucleoside analogue) arm. The percentage of patients withHIV-1 RNA <500 copies/ml was 91% in the VIRAMUNE arm, 95% in theindinavir arm and 90% in the 3TC arm. In the 'as-treatedanalysis', which accounts for patients who did not stop therapydue to toxicity or loss to follow-up, the percentage withundetectable HIV-1 RNA (<50 copies/ml) was 82% in the VIRAMUNEarm, 90% in the indinavir arm and 78% in the 3TC arm. Researchers also presented a sub-analysis of patients withhigh levels of the virus in their blood (> 51,286 copies/ml atthe start of the study) as compared to patients with a lowerviral load. In this sub analysis, the VIRAMUNE regimen also wasas effective at reducing levels of HIV as the protease inhibitorregimen in these patients, with 50% and 55% of patients reachingundetectable levels of HIV, respectively. In this same subanalysis more patients in the 3TC+d4T+ddI group had HIV-1 RNA >50copies/ml compared to the other groups after 48 weeks of therapy. Safety data for the 48-week period indicated that thetherapies were safe and generally well tolerated. Adverse eventrates were not significantly different for each treatment group. Researchers plan to follow patients in the study for more than144 weeks. The virologic effects of the three regimens on HIVreplication in lymphoid tissue, and the occurrence oflipodystrophy will also be evaluated. Additionally, a follow-upsalvage study is being initiated. MAINTAVIR Study In a "substitution" trial called MAINTAVIR, Professor FrancoisRaffi of the Centre Hospitalier Regional et Universitaire deNantes, France reports that switching to an NNRTI-based regimenfrom a protease inhibitor-based regimen simplified patients'treatment regimens and reduced the symptoms of lipodystropy whilemaintaining HIV suppression. "Our goal is to find simple treatment regimens that are well-tolerated, potent and durable," said Dr. Raffi. "Switchingpatients from a protease inhibitor to a non-nucleoside such asVIRAMUNE achieved these goals in the short-term. Our findingsshow that the majority of patients maintain undetectable levelsof HIV." Patients in the MAINTAVIR study switched from their protease-containing regimens to an NNRTI, either VIRAMUNE (47 patients) orefavirenz (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 includeadherence problems, digestive symptoms and lipodystrophy, or inmost patients, the wish to simplify the regimen. All participantshad received at least one year of protease inhibitor therapy andno prior NNRTI therapy. All patients had maintained levels of HIVbelow the limit of detection (<400 copies/ml) for at least theprevious six months. BEGIN Study The BEGIN Study explores the efficacy and tolerability ofswitching from a protease inhibitor to an NNRTI (nevirapine orefavirenz) in combination with two nucleoside analogues.Preliminary results show that an NNRTI-based treatment regimenmaintains viral suppression and offers a more tolerablealternative to PI-based therapies. Vicente Munoz, MD, Jose L. Casado, MD, et al in Madrid, Spainoffered 116 patients the option to switch to VIRAMUNE (73) orefavirenz (43) because of intolerance to protease inhibitors. Ofthe 67% of patients with undetectable levels of HIV at baseline(<200 copies/ml), 83% of them remained below 50 copies/ml after12 weeks on the NNRTI-based therapy by intent-to-treat, and 96%of them in an "as treated" analysis. Of the patients that had HIVlevels >200 copies/ml on protease inhibitor therapy, 54% achievedundetectable levels of HIV and an additional 31% achieved asignificant reduction (>1.0 log10) in levels of HIV after 12weeks on the NNRTI-based therapy. Triglycerides and cholesterolboth showed a significant decrease in those patients on an NNRTI.Adequate adherence (>95%) to the prescribed regimen increasedfrom 71% with PI-based therapy to 91% with NNRTI-based therapy(p<0.01). Twenty-eight percent of patients reported adverse events, and14% had to discontinue NNRTI treatment. The most common adverseevents were different for nevirapine or efavirenz, with 23% ofpatients with efavirenz reporting any grade of CNS disturbanceand 8% of patients with nevirapine suffering rash. VIRAMUNE VIRAMUNE is indicated for use in combination with otherantiretroviral agents for the treatment of HIV-1 infection. Thisindication is based on analysis of changes in surrogate end-points. At present, there are no results from controlled clinicaltrials evaluating the effect of VIRAMUNE in combination withother antiretroviral agents on the clinical progression of HIV-1infection, such as the incidence of opportunistic infections orsurvival. VIRAMUNE should always be administered in combinationwith at least one additional antiretroviral agent. VIRAMUNE is generally well tolerated. In clinical trials themost commonly reported adverse events associated with VIRAMUNEuse are rash, fever, nausea, headache and abnormal liver functiontests. Severe and life-threatening skin reactions andhepatotoxicity, including fatal cases of each, have occurred inpatients treated with VIRAMUNE. VIRAMUNE is a product of original research done at BoehringerIngelheim Pharmaceuticals, Inc., a member of the BoehringerIngelheim group of companies. VIRAMUNE is marketed world-wide byBoehringer Ingelheim and in the United States by RoxaneLaboratories, also a member of the Boehringer Ingelheim group ofcompanies. Boehringer Ingelheim corporation, headquartered in Ingelheim(Germany) is one of the 20 leading pharmaceutical corporations inthe world. It reported revenues exceeding DM 8.7 million in 1998. The corporation has more than 140 affiliated companies and itconducts business on every continent. Its product range isfocused on human pharmaceuticals -- hospital, prescription andself-medication -- as well as animal health. The group of companies has substantial research anddevelopment, production, and distribution facilities around theglobe. In 1998 the Boehringer Ingelheim corporation spent DM 1.6billion 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 OriginalText Service: Boehringer Ingelheim GmbH Internet:http://www.newsaktuell.de Contact: Judith von Gordon, CorporatePublic Relations Division of Boehringer Ingelheim GmbH, +49-6132-773582 or fax, +49-6132-776601; or Maureen Byrne or DeniseConnolly, both of GCI Healthcare, 212-886-3312 or 212-886-3117,or 212-886-3291

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