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 virological rebound.
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 geographic region.
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 in side-effects.
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 formulations.
"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.
Boehringer Ingelheim indicated in a press release that it is working with regulatory authorities worldwide to make the nevirapine extended-release formulation available as soon as possible.
View abstract and slides from this session on the official conference website.
Gathe J et al. 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) naïve HIV-1 infected patients (VERxVE). Eighteenth International AIDS Conference, Vienna, abstract THLBB202, 2010.