A new extended-release formulation
of nevirapine (Viramune) can be taken
once daily and performs at least as well as the older immediate-release pill,
attendees heard at a late-breaker presentation on Thursday at the Eighteenth
International AIDS Conference in Vienna.
Nevirapine, a non-nucleoside reverse
transcriptase inhibitor, is widely used as an alternative to efavirenz in first-line treatment. The immediate-release formulation currently on the market is
approved for twice-daily dosing. But once-daily medications are more convenient and
promote better adherence.
Anne-Marie Quinson from Boehringer-Ingelheim presented
findings from the VERxVE trial, which compared the safety and efficacy of
extended-release and immediate-release nevirapine formulations (Viramune XR and
Viramune IR, respectively) in previously untreated patients.
The study enrolled 1011 treatment-naive adults with
HIV. Based on studies showing that people with better-preserved immune function
are more likely to experience nevirapine hypersensitivity reactions, enrolment
was limited to men with CD4 cell counts below 400 cells/mm3 and
women below 250 cells/mm3.
During a 14-day lead-in period, all participants took
200mg immediate-release nevirapine once daily. They were then stratified
according to HIV viral load (above or below 100,000 copies/ml) and randomly
assigned in equal numbers to receive either the extended-release formulation at
400mg once daily or the immediate-release formulation at 200mg twice daily, in
combination with tenofovir/emtricitabine (Truvada).
Baseline characteristics were similar in the two study
arms. Most participants (85%) were men and the average age was 38 years. About
80% were from Europe, North America and Australia,
with smaller numbers in Latin America and Africa.
The median pre-treatment viral load was about 50,000 copies/ml and the average
CD4 cell count was 228 cells/mm3.
Analysis at 48 weeks showed that 81% of people taking
the new extended-release formulation and 76% taking the immediate-release
formulation achieved undetectable viral load below 50 copies/ml with no
The adjusted difference of 4.9% fell within the
predetermined margin of 10%, allowing the researchers to conclude that
extended-release nevirapine is non-inferior to the older formulation.
Amongst participants with high pre-treatment viral
load, response rates were lower but again comparable, 73 vs 71%, respectively.
Efficacy was similar regardless of participants' sex, baseline viral load and
Extended-release nevirapine was generally safe and
well-tolerated and no new side-effects were identified.
Types of side-effects were the same in both arms, but
occurred somewhat less often with the extended-release formulation. About 20%
of participants in the extended-release arm experienced drug-related adverse
events, compared with 24% in the immediate-release arm. Liver toxicity symptoms
were less common in the extended-release arm (about 2 vs 3%), whilst
frequencies of skin rash were similar (about 8 to 9%). Fewer extended-release
recipients dropped out because of side-effects (6 vs 9%, respectively).
A pharmacokinetic substudy showed that the extended-release formulation
met the goal of maintaining a steady concentration of nevirapine over the
dosing interval. The new formulation raised the minimum concentration and
lowered the maximum concentration, perhaps accounting for the observed reduction
Both nevirapine formulations raised total cholesterol levels, but HDL 'good' cholesterol rose more than LDL 'bad' cholesterol,
thus producing more favourable total-to-HDL ratios.
The VERxVe results showed that extended-release
nevirapine demonstrated non-inferior efficacy relative to immediate-release
nevirapine, with similar safety and tolerability profiles for both
"Once-daily dosing with Viramune
XR provides patients with
a more convenient treatment regimen with comparable efficacy and safety to
Viramune IR," the researchers concluded.
indicated in a press release that it is working with regulatory authorities
worldwide to make the nevirapine extended-release formulation available as soon