icon- folder.gif   Conference Reports for NATAP  
 
  4th IAS (Intl AIDS Society) Conference on HIV Pathogenesis, Treatment and Prevention
Sydney, Australia
22-25 July 2007
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A Randomized Comparative Trial of First-line Antiretroviral Therapy with Regimens Containing Either Nevirapine, or Efavirenz, Together with Stavudine and Lamivudine. Three-Year Extended Follow-Up of the 2NN Study.
 
 
  Reported by Jules Levin
4th IAS Conference, July 2007, Sydney, Australia
 
Ferdinand Wit 1*, Prahpan Phanuphak 2, Kiat Ruxrungtham 2, Ezio Baraldi 3, Niel Malan 4, Steven Miller 5, Naas van der Westhuizen 6, Ashraf Grimwood 7, Holger Gellermann 8, Joep Lange 1,9, for the 2NN study group. 1 International Antiviral Therapy Evaluation Center, Amsterdam, the Netherlands; 2 HIVNAT, Bangkok, Thailand; 3 Embassy Drive Medical Centre, Pretoria, South Africa; 4 Triple M Res, Port Elizabeth, South Africa; 5 Innovir Institute, Johannesburg, South Africa; 6 Christiaan Barnard Hospital, Cape Town, South Africa; 7 Woodstock, Cape Town, South Africa; 8 Boehringer Ingelheim, Ingelheim, Germany; 9 Academic Medical Center, Amsterdam, the Netherlands
 
AUTHOR CONCLUSIONS
There were no statistically significant differences with regard to the primary endpoint, treatment failure.
 
With regard to the secondary outcomes, there were no statistically significant differences in:
-- % of patients with pVL < 50 / 400 c/mL at each study week;
-- Changes in CD4+ T-cell counts;
-- Incidence of adverse events & disease progression.
 
Overall conclusions:
-- Change of medication was the most frequent reason for treatment failure;
-- There was a low incidence of virologic failure during the 2nd and 3rd year;
-- There was a continued increase in CD4+ T-cell counts;
-- There was a low rate of disease progression / death.
 
SUMMARY
Treatment success: 57.5% NVP-QD; 64.3% NVP-BD; 65% EFV.
Viral failure >400 c/ml: 8.3% NVP-od; 5.8% NVP-bd; 4.9% EFV.
CD4 increase: +270 NVP-qd; +274 NVP-bd; +300 EFV.
Grade 3-4 lab AEs: 9.2% NVP-od; 7.1% NVP-bd; 7.2% EFV.
Disease progression/death: 4.2% NVP-ed; 5.8% NVP-bd; 6.3% EFV.
 

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INTRODUCTION
The 2NN study was the first large (n=1216) randomized controlled comparison of an NRTI-backbone plus NVP (400 mg once daily (od), or 200 mg twice daily (bd)), or EFV (600 mg od) or their combination (NVP 400 mg od, EFV 800 mg od) in treatment-na•ve HIV-1 infected adults). In the intention to treat-analysis, after 48 weeks of treatment, overall treatment failure was similar among the single NNRTI arms (NVP-od 43.6%, NVP-bd 43.7%, EFV 37.8%), but statistically significantly higher in the NVP+EFV arm (53.1%).
 
The 2NN study demonstrated no significant differences in virologic and immunologic efficacy in the single NNRTI arms. Despite the results of the 2NN study, the question remains whether the comparability of NVP and EFV is maintained over a longer period of follow-up. Therefore, the durability of the antiretroviral treatment response is evaluated in this extension of the original 2NN study up to 3 years of treatment.
 
METHODS
The duration of the original 2NN study was 48 weeks. At the end of the original 2NN study, it was decided to retrospectively collect clinical data on the next two years of follow-up of the participants in the 2NN study. As one of the findings of the 2NN study was that the combination of NVP+EFV was associated with additional toxicity without improved antiretroviral efficacy, it was decided not collect additional data on the 2NN study participants who had been randomized to the NVP+EFV arm.
 
Patients who participated in the 2NN study, who were still under active follow-up at week 48 when the study closed and who were still being treated at the study clinic, were asked to participate in this study. For those who provided written informed consent, relevant clinical and laboratory data were collected retrospectively from the period between week 48 (i.e. the end of the initial 2NN study) and week 144 of follow-up, from available patient charts and hospital databases. In addition, for patients who died or became lost-to-follow-up after week 48, the Ethical Committee of the site where patients were under follow-up before they died or became lost-to-follow-up, were asked to grant permission for the data collection without consent of that specific patient or family (to avoid accidentally disclosing the HIV+ serostatus of these deceased patients to their families who often had never been informed about this).
 
Patients were treated according to local guidelines and not according to a study protocol. The frequency of clinic visits was also determined by local guidelines.
 
The main outcome measure was the percentage of patients with treatment failure between week 48 and 144, defined as: i) two consecutive pVL > 50 / 400 c/mL; or ii) new CDC-C event or death; or iii) change of allocated treatment (other than replacement of one or both antiretroviral agents of the NRTI-backbone). Secondary outcome measures were: i) the percentage of patients with pVL < 50 / 400 c/mL at each study week; ii) changes in CD4+ T-cells; and iii) incidence of adverse events & disease progression. The pre-defined comparisons were between NVP-bd vs. EFV, and between NVP-bd vs. NVP-od. No adjustments were made for multiple comparisons.

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TREATMENT FAILURE
There were no statistically significant differences between the three groups with regard to the failure component between week 49 and 144.Success Rate: NVP BD: 64.3%; NVP QD: 57.5%; EFV: 65%. Viral failure >400 c/ml: 5.8% NVP-BD; 4.9% EFV; 8.3% NVP-QD.

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