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JAC Advance Access published online on November 25, 2008
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkn471
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© The Author 2008. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Original research

High rate of early virological failure with the once-daily tenofovir/lamivudine/nevirapine combination in naive HIV-1-infected patients

D. Rey1,*, B. Hoen2, P. Chavanet3, M. P. Schmitt4, G. Hoizey5, P. Meyer6, G. Peytavin7, B. Spire8, C. Allavena9, M. Diemer10, T. May11, J. L. Schmit12, M. Duong3, V. Calvez13 and J. M. Lang1

1 COREVIH, Hôpitaux Universitaires, Strasbourg, France 2 Service des Maladies infectieuses et Tropicales, CHU Besançon, France 3 Service des Maladies infectieuses et Tropicales, CHU Dijon, France 4 Laboratoire de Virologie, Hôpitaux Universitaires, Strasbourg, France 5 Laboratoire de Pharmacologie et Toxicologie, CHU de Reims, France 6 Unité de Biostatistiques, Faculté de Médecine, Strasbourg, France 7 Laboratoire de Toxicologie et Pharmacocinétique, Hôpital Bichat, Paris, France 8 INSERM U912, Marseille, France 9 Service des Maladies infectieuses et Tropicales, CHU Nantes, France 10 Service de Médecine Interne, Hôpital Lariboisière, Paris, France 11 Service des Maladies infectieuses et Tropicales, CHU Nancy, France 12 Service des Maladies infectieuses et Tropicales, CHU Amiens, France 13 Laboratoire de Virologie, Hôpital Pitié Salpétrière, Paris, France

Received 21 July 2008; returned 11 September 2008; revised 14 October 2008; accepted 18 October 2008

* Corresponding author. COREVIH, Clinique Médicale A, Hôpitaux Universitaires, 1 place de l'Hôpital, 67091 Strasbourg Cedex, France. Tel: +33-3-88-11-63-33; Fax: +33-3-88-11-64-51; E-mail: david.rey{at}chru-strasbourg.fr

Background: The combination of one non-nucleoside reverse transcriptase inhibitor (NNRTI) with two nucleoside reverse transcriptase inhibitors is a validated first-line antiretroviral (ARV) therapy. The once-daily combination of lamivudine, tenofovirDF and nevirapine has not been evaluated in a clinical trial.

Methods: Randomized, open-label, multicentre, non-inferiority trial comparing lamivudine, tenofovirDF and nevirapine once daily (Group 2) with zidovudine/lamivudine and nevirapine twice daily (Group 1), in naive HIV-1-infected patients with a CD4 count <350/mm3. We planned to enrol 250 patients.

Results: As of May 2006, 71 patients had been enrolled (35 in Group 1 and 36 in Group 2) and an unplanned interim analysis was done. The groups were comparable at baseline: median CD4 count was 195 and 191/mm3 and median plasma viral load was 4.9 log10 and 5.01 log10, respectively, in Groups 1 and 2. Eight early non-responses (22.2%) were observed, all in Group 2, while two later viral rebounds occurred. Resistance genotypes for the nine Group 2 failing patients showed the mutations M184V/I (n = 3), K65R (n = 6), one or more NNRTI resistance mutations in all cases. At baseline, the nine Group 2 patients who failed had higher median plasma viral load (5.4 log10) and lower median CD4 count (110/mm3) than the other Group 2 patients (4.7 log10, P = 0.002 and 223/mm3, P = 0.004). Nevirapine trough concentrations were not different between the two groups, nor between patients with full viral suppression or those who failed in Group 2. Due to slow recruitment, and those results, the steering committee decided to stop the trial at 12 months.

Conclusions: In ARV-naive HIV-1-infected patients, the once-daily lamivudine, tenofovirDF and nevirapine regimen resulted in a high rate of early virological failures. The reasons for the failures remain unclear.

Key Words: resistance mutations , NNRTIs , plasma drug concentrations , virological failures


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J.-J. Parienti
Comment on: High rate of early virological failure with the once-daily tenofovir/lamivudine/nevirapine combination in naive HIV-1-infected patients
J. Antimicrob. Chemother., May 1, 2009; 63(5): 1080 - 1080.
[Full Text] [PDF]

Home page
 J Antimicrob ChemotherHome page
D. Rey, B. Hoen, P. Chavanet, M. P. Schmitt, G. Hoizey, P. Meyer, G. Peytavin, B. Spire, C. Allavena, M. Diemer, et al.
High rate of early virological failure with the once-daily tenofovir/lamivudine/nevirapine combination in naive HIV-1-infected patients--authors' response
J. Antimicrob. Chemother., May 1, 2009; 63(5): 1080 - 1081.
[Full Text] [PDF]


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