JAC Advance Access originally published online on May 6, 2009
Journal of Antimicrobial Chemotherapy 2009 64(1):118-125; doi:10.1093/jac/dkp146
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Original research |
Efficacy and safety of ritonavir-boosted dual protease inhibitor therapy in antiretroviral-naive HIV-1-infected patients: the 2IP ANRS 127 study
1 Service des Maladies Infectieuses et Tropicales, AP-HP, Groupe Hospitalier Bichat-Claude Bernard, Paris F-75018, France 2 INSERM SC10, Villejuif F-94807, France 3 Laboratoire de Virologie, AP-HP, Groupe Hospitalier Bichat-Claude Bernard, Paris F-75018, France 4 Université Paris Diderot, Paris 7, Paris, France 5 Pharmacie, AP-HP, Groupe Hospitalier Bichat-Claude Bernard, Paris F-75018, France 6 Service de Maladies Infectieuses et Tropicales, AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Paris F-75013, France 7 Université Pierre et Marie Curie, Paris 6, Paris, France 8 Service de Maladies Infectieuses et Tropicales, AP-HP, Hôpital Tenon, Paris F-75020, France 9 Service de Maladies Infectieuses et Tropicales, AP-HP, Hôpital Avicennes, Bobigny F-93009, France
Received 14 January 2009; returned 20 February 2009; revised 26 March 2009; accepted 28 March 2009
* Corresponding author. Service des Maladies Infectieuses et Tropicales, Groupe Hospitalier Bichat Claude-Bernard, 46 rue Henri Huchard, 45877 Paris Cedex 18, France. Tel: +33-1-40-25-63-67; Fax: +33-1-40-25-72-15; E-mail: roland.landman{at}paris7.jussieu.fr
Objectives: We evaluate the efficacy and tolerability of ritonavir-boosted dual protease inhibitor as a nucleoside reverse transcriptase inhibitor-sparing regimen in a prospective open-label randomized pilot trial in antiretroviral-naive patients.
Methods: Thirty patients received fosamprenavir/atazanavir/ritonavir (Group 1) and 31 patients received saquinavir/atazanavir/ritonavir (Group 2). The primary endpoint for efficacy was the rate of early virological success, defined as plasma viral load <50 copies/mL at week 16. The study is registered with ClinicalTrials.gov (NCT00122603 [ClinicalTrials.gov] ).
Results: At baseline, median (range) viral load was 4.8 log10 copies/mL (4.0–5.7) and the median CD4 cell count was 271/mm3 (197–740). Viral load was <50 copies/mL in 12/30 patients [40%, 95% confidence interval (CI) 23%–58%] and 13/31 patients (42%, 95% CI 25%–59%) at week 16 in Groups 1 and 2, respectively. Patients with failing regimens (viral load 
400 copies/mL at week 16 or 50 copies/mL at week 24) were switched to a standard antiretroviral regimen. At week 48, by an intention-to-treat analysis, 23/30 patients (77%) and 26/31 patients (84%) had plasma HIV-1 RNA <50 copies/mL in Groups 1 and 2, respectively. Four patients discontinued treatment for adverse events, all before week 4. No major changes in the protease gene were detected at treatment failure relative to baseline. Baseline viral load <50 000 copies/mL was the only predictor of virological success at week 16.
Conclusions: Ritonavir-boosted dual protease inhibitor regimens targeting only one step of viral replication were insufficient to rapidly suppress plasma HIV RNA to <50 copies/mL in antiretroviral-naive patients with high viral load at baseline.
Keywords: atazanavir , saquinavir , fosamprenavir
Members of the ANRS 127 study group are listed in the Acknowledgements section.