3-year Extended Follow-up of the 2NN Study: Nevirapine (Viramune) versus Efavirenz (Sustiva)

Clinical trial data and real-world experience have shown the non-nucleoside reverse transcriptase inhibitors (NNRTIs) to be an important class of agents for the treatment of HIV. Given their long plasma half-lives, potency against HIV, low pill burdens, and ability to be safely combined with other commonly used medications, the NNRTIs nevirapine (Viramune) and efavirenz (Sustiva) are widely used in combination antiretroviral therapies.

Prior cohort studies among antiretroviral treatment-naive patients have suggested that efavirenz may be superior to nevirapine in terms of efficacy. However, data published in 2005 from the 2NN study (2 non-nucleosides), a large (n=1216), multicenter, multinational, prospective, randomized, head-to-head trial comparing efavirenz and nevirapine, found that treatment-naive patients achieved comparably good antiviral responses using the nucleoside reverse transcriptase inhibitors (NRTIs) d4T (stavudine, Zerit) and 3TC (lamivudine, Epivir) with either efavirenz or nevirapine. After 48 weeks, 70% of patients taking efavirenz, 65% of those taking twice-daily nevirapine, and 70% of those taking once-daily nevirapine achieved viral loads below 50 copies/mL.

In a poster session at the recent 4th International AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention in Sydney, Australia (July 22-25, 2007), Ferdinand Wit, MD, of the Netherlands and colleagues presented 3-year extended follow-up data from the 2NN trial. The 2NN investigators retrospectively collected data up to 144 weeks for patients still under active follow-up at week 48. Patients in the nevirapine + efavirenz arm were not included.

The primary endpoint was the percentage of treatment failures between weeks 49 and 144, defined as the occurrence of a CDC category B/C event or death, or virological failure, or change of allocated NNRTI. Secondary endpoints included percentage of patients with virological failure, change in CD4 cell count, incidence of CDC category B/C events, and incidence of laboratory grade 3/4 (serious or severe) adverse events.

Two comparisons were made: nevirapine twice-daily vs efavirenz, and nevirapine twice-daily vs nevirapine once-daily.

Results

• 567 patients were included in the ITT analysis (120 nevirapine once-daily, 223 efavirenz, and 224 nevirapine twice-daily);

• From week 49 through week 144, treatment failure occurred in 45% of patients taking nevirapine once-daily, 35% of those taking efavirenz, and 36% of those taking nevirapine twice-daily (nevirapine once-daily vs nevirapine twice-daily P=0.24; nevirapine twice-daily vs efavirenz P=0.92).

• Both comparisons for all secondary analyses yielded no significant differences among treatment regimens.

• Virological failure occurred in 8.3% of patients taking nevirapine once-daily, 4.9% of those taking efavirnez, and 5.8% of those taking nevirapine twice-daily.

• The mean changes in CD4 cell counts from week 49 through week 144 were 72 cells/mm3 in patients taking nevirapine once-daily, 130 cells/mm3 in those taking efavirenz, and 135 cells/mm3 in those taking nevirapine twice-daily.

• Rates of grade 3/4 laboratory toxicities were 9.2% among patients taking nevirapine once-daily, 7.2% among those taking efavirenz, and 7.1% among those taking nevirapine twice-daily.

• CDC category B/C events or death occurred in 4.2% of patients taking nevirapine once-daily, 6.3% of those taking efavirenz, and 5.8% of those taking nevirapine twice-daily.

Conclusion

The study investigators concluded, "This retrospective study suggests that the virologic and immunologic response between 49 weeks and 144 weeks was comparable for the three study arms. CD4 counts were still increasing up to 144 weeks."

They added that, "Both the primary and the secondary analyses showed no statistically significant differences for efavirenz vs nevirapine twice-daily and for nevirapine once-daily vs nevirapine twice-daily."

International Antiviral Therapy Evaluation Center, Amsterdam, Netherlands; HIVNAT, Bangkok, Thailand; Embassy Drive Medical Centre, Pretoria, South Africa; Triple M Res, Port Elizabeth, South Africa; Innovir Institute, Johannesburg, South Africa; Christiaan Barnard Hospital, Cape Town, South Africa; Woodstock, Cape Town, South Africa; Boehringer Ingelheim, Ingelheim, Germany; Academic Medical Center, Department of Internal Medicine, Amsterdam, Netherlands.

08/07/07

Reference
F Wit, P Phanuphak, K Ruxrungtham, and others (for the 2NN study group). Three-year extended follow-up of the 2NN study: a randomised comparative trial of first-line antiretroviral therapy with regimens containing either nevirapine, efavirenz or both drugs combined, together with stavudine and lamivudine. 4th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention, July 22-25, 2007. Sydney, Australia. Abstract (poster) WEPEB032.