JAC Advance Access originally published online on April 29, 2009
Journal of Antimicrobial Chemotherapy 2009 64(1):126-134; doi:10.1093/jac/dkp141
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Original research |
A randomized trial of two-drug versus three-drug tenofovir-containing maintenance regimens in virologically controlled HIV-1 patients
1 Service des Maladies Infectieuses et Tropicales, Hôpital Saint-Antoine, Assistance Publique-Hôpitaux de Paris, Université Paris VI, Paris, France 2 Service des Maladies Infectieuses et Tropicales, Hôpital Z. Quitman, Fort de France, France 3 Service des Maladies Infectieuses et Tropicales, Hôpital Pontchaillou, Rennes, France 4 Service des Maladies Infectieuses et Tropicales, Hôpital de Caen, France 5 Service des Maladies Infectieuses et Tropicales, Hôpital Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Université Paris VI, Paris, France 6 Service de Médecine Interne, Hôpital Saint-André, Bordeaux, France 7 Laboratoire de Virologie, Hôpital Saint-Antoine, Assistance Publique-Hôpitaux de Paris, Université Paris VI, Paris, France 8 Gilead Sciences, Paris, France 9 INSERM U593, Université Victor Segalen Bordeaux 2, ISPED, Bordeaux, France
Received 31 October 2008; returned 5 February 2009; revised 25 March 2009; accepted 28 March 2009
* Corresponding author. Tel: +33-1-49-28-24-38; Fax: +33-1-49-28-31-49; E-mail: pierre-marie.girard{at}sat.aphp.fr
Objectives: To assess simplified maintenance regimens containing dual antiretroviral drugs in patients with controlled human immunodeficiency virus type 1 infection.
Methods: A non-inferiority, randomized, multicentre, open-label trial was performed in 24 AIDS clinical centres in France randomizing 143 patients [treated for 
6 months, plasma viral load (pVL) <50 copies/mL, no prior history of treatment failure] to receive a two-drug regimen [tenofovir disoproxil fumarate (tenofovir DF) and efavirenz] or to maintain a three-drug treatment (tenofovir DF, lamivudine and efavirenz). The main outcome measure was the success rate (percentage of patients with pVL <50 copies/mL without treatment modifications) at week 48.
Results: Success rates for the intention-to-treat analysis were 97.2% (70/72) versus 81.7% (58/71) in the three-drug versus two-drug maintenance regimen groups, respectively [difference, 15.5%; upper limit of one-sided 95% confidence interval (CI), 23.7%], and 100% (70/70) versus 90% (54/60) for the per protocol analysis, respectively (difference, 10%; upper limit of one-sided 95% CI, 16.4%), with a non-inferiority margin set at 14%. Three patients from the two-drug group experienced virological failure with selection of efavirenz-associated mutations. Overall, CD4 counts were significantly increased from baseline (median, +24 cells/mm3; P = 0.007). Four patients discontinued study treatment due to adverse events in the two-drug group and none in the three-drug group. No significant changes in creatinine clearance or phosphataemia were reported. Overall, levels of triglycerides, total and high-density lipoprotein cholesterol were improved; low-density lipoprotein cholesterol was improved only in the three-drug group.
Conclusions: The non-inferiority of the two-drug versus the three-drug regimen was not demonstrated. Lipid parameters improved after switching from twice-daily highly active antiretroviral therapy (HAART) to once-daily tenofovir-based HAART.
Keywords: HIV infection , simplification therapy , HIV-1 RNA , CD4 T lymphocytes , lipid abnormalities
Members of the COOL Study Team are listed in the Acknowledgements section.