Comparison of first-line antiretroviral therapy with regimens including nevirapine, efavirenz, or both drugs, plus stavudine and lamivudine: a randomised open-label trial, the 2NN Study

Nevirapine versus efavirenz for patients co-infected with HIV and tuberculosis: a randomised non-inferiority trial

“…19 Finally, the 48 week effi cacy of the nevirapine regimen in our study (64·6%) was in the range (61-69%) reported from randomised trials that used the same regimen in patients with HIV without tuberculosis co-infection. 23,[26][27][28] The hypothesis that nevirapine has a lower intrinsic antiviral potency than does efavirenz is also supported by recent results of the HIV-CAUSAL prospective cohort 29 which reported 54% more virological failures in patients after 12 months on an nevirapine regimen than on an efavirenz regimen, and by a review 30 of studies comparing nevirapine and efavirenz in tenofovir-based regimens, which concluded that nevirapine regimens also show increased rates of virological failure. Our results diff er from those obtained in the two previous randomised trials comparing nevirapine-based and efavirenz-based regimens in patients co-infected with HIV and tuberculosis (panel).…”

“…Assuming a 70% effi cacy in the efavirenz group 23 and a maximum diff erence of 10% in effi cacy between two groups, a sample size of 260 patients per group was needed to determine non-inferiority with a power of 80% and an α level of 5% (one-sided test; nQuery Advisor version 6). We increased the proposed sample size by 10% to account for loss to follow-up.…”

“…Indeed, the large non-inferiority randomised clinical 2NN trial 23 comparing nevirapine-based and efavirenzbased regimens in patients with HIV but not tuberculosis reported no signifi cant diff erences in virological effi cacy between groups at 48 weeks (HIV-1 RNA threshold of 50 copies per mL). A Cochrane meta-analysis 25 of seven randomised clinical trials (60% of participants were from the 2NN study 23 ) also failed to show a signifi cant diff erence between the two regimens. The 2NN study 23 thus could not show the non-inferiority of the nevirapinebased regimen.…”

“…A Cochrane meta-analysis 25 of seven randomised clinical trials (60% of participants were from the 2NN study 23 ) also failed to show a signifi cant diff erence between the two regimens. The 2NN study 23 thus could not show the non-inferiority of the nevirapinebased regimen. However, several fi ndings from our study suggest that the signifi cant diff erence in virological response between the two groups could have been attributable to nevirapine's lower intrinsic potency rather than to the interaction with rifampicin.…”

“…Use of a triple nucleoside reverse transcriptase inhibitor regimen is not ideal because of its reduced effi cacy (especially in patients with a high HIV-RNA at treatment initiation) compared with the efavirenz regimen in patients with HIV without tuberculosis. 1,23,35 Replacement of rifampicin by rifabutin, a weaker enzyme inducer, would preclude use of a fi xeddose combination-based tuberculosis therapy (a cornerstone of the WHO tuberculosis control strategy), thereby making treatment much more expensive. 36 The use of a 600 mg maintenance dose of nevirapine has been also suggested but was associated with an increased rate of hypersensitivity reactions and premature termination of a randomised trial from Thailand.…”