François Raffi1,2, Matthieu Hanf2,3, Tristan Ferry4, Lydie Khatchatourian1,2, Véronique Joly5,6, Pascal Pugliese7, Christine Katlama8,9, Olivier Robineau10, Catherine Chirouze11, Christine Jacomet12, Pierre Delobel13,14, Isabelle Poizot-Martin15,16, Isabelle Ravaux17, Claudine Duvivier18,19,20, Amandine Gagneux-Brunon21, David Rey22, Jacques Reynes23, Thierry May24, Firouzé Bani-Sadr25, Bruno Hoen26,27, Marine Morrier28, André Cabie29, Clotilde Allavena1,2. 1. Infectious Diseases Department, University Hospital of Nantes, Nantes, France. 2. INSERM CIC 1413, Nantes University Hospital, Nantes, France. 3. INSERM UMR 1181 B2PHI, Versailles Saint Quentin University, Institut Pasteur, Villejuif, France. 4. Infectious and Tropical Diseases Department, Hospices Civils de Lyon, Claude Bernard Lyon 1 University, Lyon, France. 5. Infectious Diseases Department, Hôpital Bichat, AP-HP, Paris, France. 6. National Institute of Health and Medical Research (INSERM) IAME, UMR 1137, Paris Diderot University, Sorbonne Paris Cité, Paris, France. 7. Department of Infectious Diseases, Centre Hospitalier Universitaire de l'Archet, Nice, France. 8. Department of Infectious Diseases, Assistance publique-Hôpitaux de Paris, Pitié-Salpêtrière University Hospital, Paris, France. 9. Institut Pierre-Louis d'Epidémiologie et de Santé Publique, Unité Mixte de Recherche en Santé 1136, Inserm, Paris and Université Pierre et Marie Curie Paris 06, Sorbonne Universités, Paris, France. 10. Infectious Diseases Department, Gustave Dron Hospital, Tourcoing, France. 11. Infectious Diseases Department, University Hospital of Besançon, UMR CNRS 6249, University of Bourgogne-Franche Comté, Besançon, France. 12. Infectious Diseases Department, University of Clermont-Ferrand, Clermont-Ferrand, France. 13. INSERM, UMR1043, Toulouse and Université Toulouse III Paul Sabatier, Toulouse, France. 14. Service des Maladies Infectieuses et Tropicales, CHU de Toulouse, Toulouse, France. 15. Aix-Marseille University, APHM Hôpital Sainte-Marguerite, Immuno-Hematology Clinic, Marseille, France. 16. Inserm U912 (SESSTIM), Marseille, France. 17. Department of Infectious Diseases, Aix-Marseille University, APHM, Hôpital de La Conception, Marseille, France. 18. AP-HP-Necker Hospital, Infectious Diseases Department, Necker-Pasteur Infectiology Centre, Paris, France. 19. Medical Centre of Pasteur Institut, Necker-Pasteur Infectiology Centre, Paris, France. 20. EA7327, Paris Descartes University, Sorbonne Paris Cité, Paris, France. 21. Infectious Diseases Department, University of Saint-Etienne, Saint-Etienne, France. 22. Centre for HIV Infection Care, Strasbourg, France. 23. Infectious Diseases Department, UMI233 INSERM U1175, Montpellier University Hospital, Montpellier, France. 24. Department of Infectious Diseases, University Hospital Centre, Nancy, France. 25. Department of Internal Medicine, Infectious Diseases, and Clinical Immunology Reims Teaching Hospitals, University of Reims, Reims, France. 26. Faculté de Médecine Hyacinthe Bastaraud, Université des Antilles, Service de Maladies Infectieuses et Tropicales, Dermatologie, Médecine Interne, Point-á-Pitre, France. 27. Inserm CIC 1424, Centre Hospitalier Universitaire de Pointe-à-Pitre, Pointe-à-Pitre, France. 28. Departement of Infectious Diseases, CHD Vendee, La Roche sur yon, France. 29. Infectious Diseases Department, University Hospital of Martinique, Fort-de-France, France.
Abstract
OBJECTIVES: We investigated the risk of virological rebound in HIV-1-infected patients achieving virological suppression on first-line combined ART (cART) according to baseline HIV-1 RNA, time to virological suppression and type of regimen. PATIENTS AND METHODS: Subjects were 10 836 adults who initiated first-line cART (two nucleoside or nucleotide reverse transcriptase inhibitors + efavirenz, a ritonavir-boosted protease inhibitor or an integrase inhibitor) from 1 January 2007 to 31 December 2014. Cox proportional hazards models with multiple adjustment and propensity score matching were used to investigate the effect of baseline HIV-1 RNA and time to virological suppression on the occurrence of virological rebound. RESULTS: During 411 436 patient-months of follow-up, risk of virological rebound was higher in patients with baseline HIV-1 RNA ≥100 000 copies/mL versus <100 000 copies/mL, in those achieving virological suppression in > 6 months versus <6 months, and lower with efavirenz or integrase inhibitors than with ritonavir-boosted protease inhibitors. Baseline HIV-1 RNA >100 000 copies/mL was associated with virological rebound for ritonavir-boosted protease inhibitors but not for efavirenz or integrase inhibitors. Time to virological suppression >6 months was strongly associated with virological rebound for all regimens. CONCLUSIONS: In HIV-1-infected patients starting cART, risk of virological rebound was lower with efavirenz or integrase inhibitors than with ritonavir-boosted protease inhibitors. These data, from a very large observational cohort, in addition to the more rapid initial virological suppression obtained with integrase inhibitors, reinforce the positioning of this class as the preferred one for first-line therapy.
OBJECTIVES: We investigated the risk of virological rebound in HIV-1-infected patients achieving virological suppression on first-line combined ART (cART) according to baseline HIV-1 RNA, time to virological suppression and type of regimen. PATIENTS AND METHODS: Subjects were 10 836 adults who initiated first-line cART (two nucleoside or nucleotide reverse transcriptase inhibitors + efavirenz, a ritonavir-boosted protease inhibitor or an integrase inhibitor) from 1 January 2007 to 31 December 2014. Cox proportional hazards models with multiple adjustment and propensity score matching were used to investigate the effect of baseline HIV-1 RNA and time to virological suppression on the occurrence of virological rebound. RESULTS: During 411 436 patient-months of follow-up, risk of virological rebound was higher in patients with baseline HIV-1 RNA ≥100 000 copies/mL versus <100 000 copies/mL, in those achieving virological suppression in > 6 months versus <6 months, and lower with efavirenz or integrase inhibitors than with ritonavir-boosted protease inhibitors. Baseline HIV-1 RNA >100 000 copies/mL was associated with virological rebound for ritonavir-boosted protease inhibitors but not for efavirenz or integrase inhibitors. Time to virological suppression >6 months was strongly associated with virological rebound for all regimens. CONCLUSIONS: In HIV-1-infected patients starting cART, risk of virological rebound was lower with efavirenz or integrase inhibitors than with ritonavir-boosted protease inhibitors. These data, from a very large observational cohort, in addition to the more rapid initial virological suppression obtained with integrase inhibitors, reinforce the positioning of this class as the preferred one for first-line therapy.
Authors: Anton Reepalu; Dawit A Arimide; Taye T Balcha; Habtamu Yeba; Adinew Zewdu; Patrik Medstrand; Per Björkman Journal: Open Forum Infect Dis Date: 2021-03-06 Impact factor: 3.835