Results of the 2NN study1 published in The Lancet showed no statistically significant difference between Viramune (nevirapine, NVP) and efavirenz (EFV) in anti-HIV efficacy with respect to viral suppression and immune restoration at 48 weeks.

The 2NN study is the first large-scale, randomized trial directly comparing non-nucleoside reverse transcriptase inhibitor- (NNRTI) containing regimens in patients initiating antiretroviral therapy. NNRTIs are commonly used in combination therapy to treat patients with HIV-1 infection. All treatment arms also included the nucleoside analogue drugs stavudine and lamivudine.

"Unlike previous retrospective cohort studies, the results of this large, randomized, multi-center trial clearly demonstrate the comparable efficacy of Viramune and efavirenz in HIV treatment," said lead 2NN investigator Professor Joep Lange of the International Antiviral Therapy Evaluation Center (IATEC) and President of the International AIDS Society.

"These results provide physicians with key scientific information necessary to confidently choose an NNRTI based on the individual needs of each of their patients."

A composite end-point comprised of virologic failure, drug discontinuation, HIV disease progression/AIDS or death was reported in the study. There was no statistically significant difference between Viramune once or twice daily and efavirenz. The arm that combined both Viramune + efavirenz was statistically inferior to the efavirenz arm due to decreased tolerability, resulting in more drug discontinuations.

In the intent to treat (ITT) analysis, a viral load of less than 50 copies/mL was reached by 70 percent of the patients in the Viramune once-daily arm, 65.4 per cent in the Viramune twice-daily arm, 70 percent in the efavirenz arm and 62.7 per cent in the Viramune + efavirenz arm. The treatment arms had comparable increases in CD4 cells over 48 weeks in the ITT population.

2NN was conducted by the International Antiviral Therapy Evaluation Center (IATEC). The trial enrolled 1,216 patients from 65 centers in 17 countries. Treatment-naïve patients received the nucleoside analogues d4T (stavudine) and 3TC (lamivudine), and were randomized to one of four NNRTI treatment arms: Viramune once-daily, Viramune twice-daily, efavirenz and Viramune + efavirenz. Analyses include efficacy, safety, plasma lipid profile, quality of life, and plasma pharmacokinetics. The initial 2NN study results were first presented at the 10th Conference on Retroviruses and Opportunistic Infections (CROI) in 2003.

There was no statistical difference in the overall rates of grade 3-4 serious clinical adverse events or rates of treatment discontinuations in the single NNRTI arms. The most common adverse events experienced in the Viramune arms were rash and hepatic events. The most common adverse event experienced in the efavirenz arms was central nervous system/psychiatric events. The Viramune once-daily arm had a significantly higher incidence of grade 3 or 4 liver associated laboratory abnormalities compared to the efavirenz arm. There were twenty-five deaths among the 1,216 patients participating the study. Of these, two occurred before study medication was initiated, eleven were HIV-disease related, three were attributed to one of the drugs included in the trial participant`s triple antiretroviral combination (one attributed by the investigator to d4T and two attributed by the investigator to Viramune) and the remainder were not related to study medication, nor HIV-disease.