translation agency

PR Newswire
New VIRAMUNE(R) (nevirapine) Data Presented at International

July 10, 2001
BUENOS AIRES, July 10 /PRNewswire/ -- Preliminary findings from three studies presented this week at the first International AIDS Society Conference on HIV Pathogenesis and Treatment demonstrate that HIV-positive individuals taking a VIRAMUNE(R) (nevirapine)-based anti-HIV treatment combination were observed to have an improved lipoprotein profile following six to 12 months of therapy. Researchers examined critical criteria, including increases in HDL (high-density lipoprotein or "good") cholesterol, improvements in total cholesterol/HDL ratio and decreases in triglyceride levels.

While these preliminary data warrant further study, some of these findings suggest that VIRAMUNE may provide a potential benefit not provided by anti-HIV treatment regimens containing protease inhibitors. Some research has suggested a link may exist between the use of anti-HIV protease inhibitor-containing treatment regimens and both premature coronary artery disease and carotid atherosclerosis in HIV-positive individuals.(1,2)

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.

Sub-study of the Atlantic Trial: FRAMS

Findings from the Fat Redistribution and Metabolic Sub-study (FRAMS) of the Atlantic trial showed that patients treated with VIRAMUNE, ddI and d4T achieved an improved lipoprotein profile following 24 weeks of treatment. This was not observed in patients who received the protease inhibitor indinavir or the nucleoside analogue 3TC with the same backbone drugs (ddI and d4T).

The primary objective of this sub-study was to evaluate potential differences in patients' lipoprotein profile using three treatment strategies. For this analysis, researchers evaluated 114 representative patients of the 298 participants enrolled in the Atlantic trial. The three study arms were d4T and ddI combined with VIRAMUNE (an NNRTI), indinavir (a protease inhibitor), or 3TC (a nucleoside analogue).

Researchers determined the lipoprotein profile in prospectively collected stored plasma samples at treatment initiation and after six and 24 weeks of treatment. After 24 weeks, patients in the VIRAMUNE arm demonstrated a 49% increase from baseline in HDL cholesterol and a 14% decrease in the total cholesterol/ HDL-cholesterol ratio.

COMBINE Lipid Substudy

The FRAMS data are similar to that of the international COMBINE study, another trial presented at the conference. Findings from the COMBINE lipid sub-study demonstrate that a VIRAMUNE-based therapy resulted in a higher HDL cholesterol level and a better total cholesterol/HDL cholesterol ratio than did a combination containing the protease inhibitor nelfinavir.

A subgroup of 43 HIV-positive individuals in the COMBINE study was evaluated for body composition changes and metabolic alterations. After 12 months of therapy, 53% of nelfinavir treated patients achieved elevations in LDL (low-density lipoprotein or "bad") cholesterol, which met requirements for intervention. Fewer patients receiving the VIRAMUNE-based regimen required LDL cholesterol interventions (22.2% of patients).

COMBINE is a randomized, open-label, multicenter trial of 142 patients in 12 hospitals in Spain and Argentina. The study compares the efficacy and safety of VIRAMUNE plus Combivir to nelfinavir plus Combivir in patients who have not previously been treated with antiretroviral therapy.

Lipid Analysis: VIRAMUNE and efavirenz Studies

A third analysis evaluated the effect on a patient's cholesterol, triglycerides and body fat redistribution when the patient was switched from a protease inhibitor (PI) to a NNRTI, either VIRAMUNE (n=290) or efavirenz (n=414). After six months, mean triglyceride levels decreased 21% in patients who switched to VIRAMUNE, while there was no change in triglyceride levels in patients who switched to efavirenz. Total cholesterol improved by 7% in those who switched to VIRAMUNE versus no change in those who switched to efavirenz or maintained a PI regimen.

These data come from a composite analysis of all studies published or presented at international HIV/AIDS meetings from 1998 through 2001 that reported evolution of total plasma cholesterol and triglycerides following a switch from a PI to VIRAMUNE or efavirenz. Eighteen studies, comprising a total of 1,310 patients who switched therapy, were analyzed. There was no restriction as to the duration of PI therapy. Because this is a retrospective meta-analysis of clinical data, confounding criteria or bias should be considered in evaluating these results.


The most clinically important adverse events associated with VIRAMUNE are rash (16%) 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. Patients should be closely monitored for signs of severe hepatotoxicity or skin reactions, particularly during the first 12 weeks of therapy. 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.

VIRAMUNE is a product of original research done at Boehringer Ingelheim Pharmaceuticals, Inc., a member of the Boehringer Ingelheim group of companies.

IAS POSTER SESSION-LIPODYSTROPHY: Tuesday, July 10, 2001, 12:30-14:00 San Isidro

496 - Nevirapine-Containing Antiretroviral Therapy in HIV-1 Infected Patients Results in an Anti-Atherogenic Lipid Profile: Results from the Atlantic Study; Van Der Valk, M; Kastelein, J; Murphy, R; Katlama, C; Horban, A; Glesby, M; Reiss, P.

506 - Metabolic and Anthropometric Changes Observed in HIV-Infected Patients Treated with COMBIVIR (ZDV/3TC) Plus Nelfinavir or Nevirapine (A Substudy of the COMBINE-Study); Fisac, C; Virgili, N; Ferrer, E; Vilarasau, C; Pita, A; Lacarcel, M; Podzamczer, D.

484 - Switching Protease Inhibitor (PI) to Nevirapine (NVP) Leads to a Better Lipid Profile than Switch to Efavirenz (EFV); Imperiale, S; Carlier, H.


1. Henry K, Melroe H, Huebsch J, et al . Severe premature coronary artery disease with protease inhibitors. Lancet 1998;351: 9112.

2. Maggi, P, Serio, G, Epifani, G et al. Premature lesions of the carotid vessels in HIV-1 infected patients treated with protease inhibitors. AIDS 2000, 14: 123-8.

Antiretroviral agents referenced in this release: d4T (Zerit(R), stavudine), ddI (Videx(R), didanosine), Bristol-Myers Squibb Co.; indinavir (Crixivan(R)), Merck & Co, Inc.; 3TC (Epivir(R), lamivudine), Glaxo SmithKline Inc; efavirenz (Sustiva(TM)), DuPont Pharma; nelfinavir (Viracept(R)), Agouron Pharmaceuticals Inc.

SOURCE Boehringer Ingelheim Pharmaceuticals, Inc.