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Session 35a Oral Abstract Presentations
Clinical Trials and Cohorts
Session Day and Time: Friday 8:30 - 10:30 am
Presentation Time: 08:30
Room: Auditorium


176
Results of the 2NN Study: A Randomized Comparative Trial of First-line Antiretroviral Therapy with Regimens Containing Either Nevirapine Alone, Efavirenz Alone or Both Drugs Combined, Together with Stavudine and Lamivudine
F. van Leth1, E. Hassink1, P. Phanuphak2, S. Miller3, B. Gazzard4, P. Cahn5, R. Wood6,7, K. Squires8, C. Katlama9, B. Santos10, P. Robinson11, R. van Leeuwen1, F. Wit1, J.Lange*1,12, for the 2NN study group
1Intl Therapy Evaluation Ctr, Amsterdam, The Netherlands; 2HIV Netherlands Australia Thailand Res Collaboration, Thai Red Cross AIDS Res Ctr, Bangkok; 3Innovir Inst, Johannesburg, South Africa; 4Chelsea and Westminster Hosp, London, UK; 5Fndn Huesped, Buenos Aires, Argentina; 6Somerset Hosp, Cape Town, South Africa; 7Univ of Cape Town, South Africa; 8Keck Sch of Med, Univ of Southern Califorinia, Los Angeles, CA; 9Hosp Pitie-Salpetriere, Paris, France; 10Hosp Nossa Senhora da Conceicao, Porto Alegre, Brazil; 11Boehringer Ingelheim, Ridgefield, CT; and 12Academic Med Ctr, Amsterdam, The Netherlands

Background: The non-nucleoside reverse transcriptase inhibitors nevirapine (NVP) and efavirenz (EFV) are widely used in protease inhibitor-sparing HAART regimens. The 2NN study is the first large randomised trial directly comparing both drugs and their combination.

Methods: A multicentre, open label, randomised trial. We randomized 1,216 therapy naïve patients to NVP once daily (od), NVP twice daily (bd), EFV or NVP (od) + EFV. The NRTI backbone consisted of d4T and 3TC, but could be changed for toxicity reasons. Primary endpoint: percentage of patients (pts) with treatment failure (Rx-failure), defined as either less than 1log10 decline in plasma HIV-1 RNA (pVL) in the first 12 weeks (wks), virologic failure from wk 24 onwards, disease progression, or change of allocated treatment. Secondary endpoints: percentage of pts with pVL < 50 copies/mL, change in number of CD4 cells, and incidence of adverse clinical or laboratory events (AE). All analyzes were at wk 48 for the intention to treat population (all randomised pts).

Results: Baseline characteristics were similar for all 4 arms, including prevalence of hepatic co-infections.

 

Treatment arm

NVP(od)

NVP(bd)

EFV

NVP+EFV

 p value for Rx Groups

 

A

B

C

D

AvC

BvC

AvD

CvD

 

n = 220

n = 387

n = 400

n = 209

 

 

 

 

 

 

 

 

 

 

 

 

 

RX-failure,%

43.6

43.7

38.3

53.1

0.19

0.12

0.05

< 0.001

pVL < 50 copies/mL,%

70.0

65.4

70.0

62.7

1.00

0.17

0.11

0.07

CD4 increase, cells/mm3

170.0

160.0

160.0

150.0

0.49

0.74

0.91

0.71

clinical AE *,%

27.7

27.1

22.3

35.4

0.13

0.11

0.09

< 0.001

liver associated lab AE #, %

13.2

7.8

4.5

8.6

< 0.001

0.06

0.13

0.04

other lab AE !, %

8.2

12.9

8.8

9.6

0.81

0.06

0.61

0.74

 

* percentage patients with at least one grade 3 or 4 AE.

# ASAT, ALAT (LEE), bilirubine associated with LEE

! excluding isolated gGT

 

Conclusions: Overall Rx-failure was similar among the single nNRTI arms, but was higher in the NVP+EFV arm, mainly caused by more Rx discontinuations in this arm. The incidence of clinical adverse events did not differ significantly between the single nNRTI arms. Only the incidence in liver associated laboratory AEs was significantly different between the arms, with the highest incidence in the NVP (od) arm. The virologic and immunologic efficacy was comparable among all 4 arms.