Non-nucleoside reverse transcriptase inhibitors (NNRTIs) have become the first-line treatment of choice for HIV infections, as clinicians seek long-term therapies that can avoid some of the adverse effects seen with protease inhibitor-based regimens. A general perception exists among clinicians that efavirenz-based highly active antiretroviral therapy (HAART) is superior to nevirapine-based regimens. However, the 2NN study, the first major head-to-head comparison of efavirenz- and nevirapine-based HAART and a regimen containing both NNRTIs, showed that the two agents were equally effective. These data, presented at the 10thConference on Retroviruses and Opportunistic Infections [Boston, US; February 2003] showed that nevirapine- and efavirenz-based regimens were equally effective in reducing viral load and increasing CD4+ cell counts, with comparable rates of treatment failure. Furthermore, there was no significant difference between the two agents in the proportions of patients experiencing serious clinical adverse events."The results of this large, randomized, prospective, multi-center trial clearly demonstrate the comparable efficacy of nevirapine and efavirenz in HIV treatment", said the study's lead investigator, Dr Joep Lange from the Academic Medical Center of the University of Amsterdam, The Netherlands. Interestingly, the regimen containing both efavirenz and nevirapine was the least effective, and was associated with higher incidences of serious adverse events and laboratory abnormalities than those containing efavirenz or nevirapine alone.