Extended Release Nevirapine (Viramune) Equals Twice-daily Immediate Release
A once-daily extended-release formulation of nevirapine
(Viramune) suppresses HIV viral load as well as the older
immediate-release pill, and may cause fewer or milder side
effects, according to a late-breaker presentation at the XVIII
International AIDS Conference (AIDS
2010) last week in Vienna. The more convenient once-daily
formulation is likely to be especially beneficial in resource-limited
countries where the drug is still widely used.
formulation of nevirapine (Viramune IR) currently on the market is approved
for twice-daily dosing. Once-daily medications, however, are more convenient
and associated with better adherence.
by Anne-Marie Quinson from Boehringer-Ingelheim, the VERxVE trial compared
the safety and efficacy of extended-release (Viramune XR) and immediate-release
nevirapine formulations for first-line HIV treatment.
enrolled 1011 treatment-naive HIV positive adults, mostly from North
America, Europe, and Australia. Most (85%) were men and the average
age was 38 years.
pre-treatment viral load was about 50,000 copies/mL, and participants
were stratified into high and low viral load groups (above or below
100,000 copies/mL). The average CD4 cell count was 228 cells/mm3. (Based
on studies showing that people with better immune function are more
likely to experience nevirapine hypersensitivity reactions, men with
CD4 counts above 400 cells/mm3 and women with levels above 250 cells/mm3
a 14-day lead-in period -- done to bring nevirapine up to therapeutic
levels in the body -- all participants took 200 mg Viramune IR once-daily.
They were then randomly assigned (1:1) to receive either Viramune IR
at a dose of 200 mg twice-daily or the new Viramune XR at a dose of
400 mg once-daily, both in combination with tenofovir/emtricitabine
48 week analysis showed that 81% of patients taking the new Viramune
XR achieved undetectable viral load (< 50 copies/mL) with no
virological rebound, compared with 76% of those taking the Viramune
adjusted difference of 4.9% fell within a predetermined margin of
10%, indicating that Viramune XR is non-inferior to the immediate-release
rates were also similar among participants with high baseline viral
load, at 73% vs 71%, respectively.
XR was generally safe and well-tolerated.
of Viramune XR recipients and 19% taking Viramune IR discontinued
treatment prior to week 48.
and 8%, respectively, did so due to adverse events.
of participants in the Viramune XR arm experienced drug-related
adverse events compared with 24% in the Viramune IR arm, not a significant
vs 11%, respectively, experienced serious adverse events.
and 9%, respectively, had adverse events leading to treatment discontinuation.
of adverse events were similar in both arms but occurred somewhat
less often with Viramune XR.
liver toxicity was less common in the Viramune XR arm than in the
Viramune IR arm (1.6% vs 2.8%).
rash occurred with similar frequency in the 2 arms (8.3% vs 8.7%,
formulations demonstrated similar blood lipid profiles, lowering
triglycerides and raising total, LDL ("bad"), and HDL
XR, however, was associated with a slightly better total cholesterol-to-HDL
a subset of participants in a pharmacokinetic sub-study, Viramune
XR maintained a steady nevirapine concentration over the dosing
interval, raising the minimum concentration seen with Viramune IR
while lowering the maximum concentration.
trial showed "non-inferior efficacy for Viramune XR to Viramune
IR," the investigators summarized, with "similar safety and
tolerability profiles for both formulations."
dosing with Viramune XR provides patients with a more convenient treatment
regimen with comparable efficacy and safety to Viramune IR," they
"We are confident that the extended release formulation, once approved,
will enable HIV patients and their physicians to choose an effective,
tolerable and durable treatment option with a favourable lipid profile,"
Prof. Klaus Dugi, Boehringer Ingelheim Corporate Senior Vice President
Medicine, said in a press release issued by the company. "This
development is particularly important as it will give patients the convenience
of a once daily antiretroviral drug that does not carry food or drink
Boehringer Ingelheim indicated that it is working with regulatory authorities
to make the nevirapine extended-release formulation available on a global
basis as soon as possible.
Therapeutic Concepts, Houston, TX; Ludwig-Maximilians University,
Munich, Germany; Care Resource, Miami, FL; Warsaw Medical University
and Hospital of Infectious Diseases, Warsaw, Poland; Chelsea & Westminster
Hospital, London, UK; Fundacion Huesped, Buenos Aires, Argentina; Antiguo
Hospital Civil de Guadalajara, Guadalajara, Mexico; Toga Labs, Edenvale,
South Africa; Boehringer-Ingelheim Pharmaceuticals Inc, Ridgefield,
J Gathe, J Bogner, S Santiago, and others. Comparison of 48 week efficacy
and safety of 400 mg QD nevirapine extended release formulation (Viramune
XR) versus 200 mg BID nevirapine immediate release formulation (Viramune
IR) in combination with Truvada in antiretroviral (ARV) naive HIV-1
infected patients (VERxVE). XVIII International AIDS Conference (AIDS
2010). Vienna, July 18-23, 2010. Abstract THLBB202.
Boehringer-Ingelheim. VERxVE study demonstrates efficacy and safety
of 400mg once daily nevirapine (Viramune) extended release (NVP XR)
formulation. Press release. July 22, 2010.