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
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/
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
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
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
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.