2NN Slides 2005 mb

The 2NN study: 

The 2NN study A randomised comparative open label trial of first-line antiretroviral therapy with regimens containing either nevirapine, efavirenz, or both drugs combined in addition to stavudine and lamivudine F. van Leth, E. Hassink, P. Phanuphak, S. Miller, B. Gazzard, P. Cahn, R. Wood, K. Squires, F. Raffi, C. Katlama, B. Santos, P. Robinson, R. van Leeuwen, F. Wit and J. Lange for the 2NN study team

Participating countries: 

Participating countries 17 countries 65 centers

Trial design: 

Trial design Nucleoside backbone: d4T and 3TC Inclusion criteria: pVL > 5000 copies/mL any CD4 cell count any stage of CDC-classification

Outcome measures: 

Outcome measures % of patients with treatment failure at week 48: less than 1log10 decline in pVL in first 12 weeks 2 consecutive pVL > 50 copies/mL from week 24 onwards new CDC-C event or death change of allocated treatment Secondary outcomes: % of patients with pVL < 50 copies/mL at each study week change in CD4+ cells incidence of adverse events change in lipid concentrations (poster 752)

Methods: 

Methods All analyses Intention-to-Treat (unless stated otherwise) all randomised patients pVL data: missing=failure Four pre-defined pairwise comparisons NVP-bd vs EFV NVP-od vs NVP-bd NVP-od vs NVP+EFV EFV vs NVP+EFV

Trial Flow: 

Trial Flow

Baseline characteristics: 

Baseline characteristics

Treatment success and failure: 

Treatment success and failure Success: only significant difference: EFV vs NVP+EFV, p< 0.001

Virologic success: 

Virologic success No significant differences in any of the pairwise comparisons

Virologic successby baseline pVL: 

Virologic success by baseline pVL

pVL < 50 copies/mLITT: 

pVL < 50 copies/mL ITT

pVL < 50 copies/mLOT: 

pVL < 50 copies/mL OT

Increase in CD4 cellsOT: 

Increase in CD4 cells OT

Grade 3 or 4 clinical adverse events(all isolated laboratory events excluded): 

Grade 3 or 4 clinical adverse events (all isolated laboratory events excluded) * patients with at least one grade 3/4 event. † patients temporarily or permanently discontinuing Rx because of AE (any grade)

Grade 3 or 4 laboratory toxicities: 

Grade 3 or 4 laboratory toxicities hepatobiliary: only significant difference: NVP-od vs EFV, p< 0.001

Deaths: 

Deaths 25 patients died during the study: 2 deaths attributed to NVP use female from Argentina with toxic hepatitis without evidence of hepatic co-infection Steven’s Johnson syndrome from S. Africa. Died of MRSA septicaemia while recovering in hospital 1 death attributed to d4T use lactic acidosis 11 deaths related to HIV-disease 11 deaths non-Rx and non-HIV related none of suicides attributed to use of study medication

Changes in lipid concentrations: 

Changes in lipid concentrations Both NVP-only arms, compared to EFV: larger increase in HDL-c larger decrease in TC:HDL-c ratio

Summary: 

Summary

Conclusions: 

Conclusions NVP and EFV have comparable potency in suppressing HIV-1 replication NVP-od and NVP-bd show comparable efficacy Co-administration of NVP and EFV results in higher treatment failure due to increased toxicity

Acknowledgements (1): 

Acknowledgements (1)

Acknowledgements (2): 

Acknowledgements (2)

Abstract authors: 

Abstract authors Pedro Cahn Christine Katlama Remko v. Leeuwen Ferdinand Wit Joep Lange François Raffi Frank van Leth Steve Miller Pat Robinson Robin Wood Elly Hassink Brian Gazzard Prahpan Phanuphak Kathleen Squires Breno Santos