Jean-Luc Meynard1, Laetitia Moinot2, Roland Landman3,4, Laurence Morand-Joubert1,5, Amel Besseghir2, Sami Kolta6,7, Bruno Spire8,9,10, Eve Todesco11,12, Olivier Bouchaud13, Catherine Fagard2, Geneviève Chene2,14, Pierre-Marie Girard1,5. 1. AP-HP, Hôpital Saint-Antoine, Paris, France. 2. Univ. Bordeaux, ISPED, INSERM Bordeaux Population Health Research Center, UMR 1219, CIC1401-EC, CHU Bordeaux, F-33000 Bordeaux, France. 3. IAME, UMR 1137, Univ Paris Diderot, Sorbonne Paris Cité, AP-HP, Hôpital Bichat-Claude Bernard, Service de Maladies Infectieuses et Tropicales, F-75018 Paris, France. 4. IMEA, Institut de médecine et d'épidémiologie appliquée, Hôpital Bichat-Claude Bernard, Paris, France. 5. Sorbonne Universités, UPMC Univ Paris 06, INSERM, Institut Pierre Louis d'épidémiologie et de Santé Publique (IPLESP UMRS 1136), F75013 Paris, France. 6. Department of Rheumatology, Cochin Hospital en français, Assistance Publique- Hôpitaux de Paris, Paris, France. 7. INSERM UMR-1153, Paris, France. 8. INSERM, UMR912 (SESSTIM), Marseille, France. 9. Aix Marseille Univ., UMR_S912, IRD, Marseille, France. 10. ORS PACA, Observatoire Régional de la Santé Provence-Alpes-Côte d'Azur, Marseille, France. 11. Sorbonne Universités, UPMC Univ Paris 06, INSERM, Institut Pierre Louis d'épidémiologie et de Santé Publique (IPLESP UMRS 1136), Paris F75013, France. 12. Department of Virology, Hôpital Pitié-Salpétrière, AP-HP, Paris F75013, France. 13. AP-HP, Hôpital Avicenne, Bobigny, France. 14. CHU de Bordeaux, Pôle de Santé Publique, Service d'information médicale, F-33000 Bordeaux, France.
Abstract
Background: Sparing of antiretroviral drug classes could reduce the toxicity and cost of maintenance treatment for HIV infection. Objectives: To evaluate the non-inferiority of efficacy and the safety of lopinavir/ritonavir (r) monotherapy versus a single-tablet regimen of efavirenz, emtricitabine and tenofovir (EFV/FTC/TDF) over 2 years. Methods: Adults on stable ART with plasma HIV-1 RNA viral load <50 copies/mL for the past 12 months and no documented treatment failure were randomized to receive either lopinavir/r or EFV/FTC/TDF for 2 years. The primary endpoint was the proportion of patients without treatment failure at week 96 (viral load <50 copies/mL at week 96, confirmed at week 98), without study treatment discontinuation, a new AIDS-defining illness, or death. Results: In the ITT analysis, the primary endpoint was reached by, respectively, 64% and 71% of patients in the lopinavir/r (n = 98) and EFV/FTC/TDF arms (n = 97), yielding a difference of -6.8% (lower limit of the 95% two-sided CI: -19.9%). Sanger and UltraDeep sequencing showed the occurrence of PI mutations in the lopinavir/r arm (n = 4) and of NNRTI and/or NRTI mutations in the EFV/FTC/TDF arm (n = 2). No unexpected serious clinical events occurred. Conclusions: Lopinavir/r monotherapy cannot be considered non-inferior to EFV/FTC/TDF. PI resistance rarely emerged in the lopinavir/r arm and did not undermine future PI options. Two years of lopinavir/r monotherapy had no deleterious clinical impact when compared with EFV/FTC/TDF.
RCT Entities:
Background: Sparing of antiretroviral drug classes could reduce the toxicity and cost of maintenance treatment for HIV infection. Objectives: To evaluate the non-inferiority of efficacy and the safety of lopinavir/ritonavir (r) monotherapy versus a single-tablet regimen of efavirenz, emtricitabine and tenofovir (EFV/FTC/TDF) over 2 years. Methods: Adults on stable ART with plasma HIV-1 RNA viral load <50 copies/mL for the past 12 months and no documented treatment failure were randomized to receive either lopinavir/r or EFV/FTC/TDF for 2 years. The primary endpoint was the proportion of patients without treatment failure at week 96 (viral load <50 copies/mL at week 96, confirmed at week 98), without study treatment discontinuation, a new AIDS-defining illness, or death. Results: In the ITT analysis, the primary endpoint was reached by, respectively, 64% and 71% of patients in the lopinavir/r (n = 98) and EFV/FTC/TDF arms (n = 97), yielding a difference of -6.8% (lower limit of the 95% two-sided CI: -19.9%). Sanger and UltraDeep sequencing showed the occurrence of PI mutations in the lopinavir/r arm (n = 4) and of NNRTI and/or NRTI mutations in the EFV/FTC/TDF arm (n = 2). No unexpected serious clinical events occurred. Conclusions: Lopinavir/r monotherapy cannot be considered non-inferior to EFV/FTC/TDF. PI resistance rarely emerged in the lopinavir/r arm and did not undermine future PI options. Two years of lopinavir/r monotherapy had no deleterious clinical impact when compared with EFV/FTC/TDF.