Maintenance darunavir/ritonavir monotherapy to prevent perinatal HIV transmission, ANRS-MIE 168 MONOGEST study
Author:
Mandelbrot Laurent123ORCID, Tubiana Roland45, Frange Pierre26ORCID, Peytavin Gilles37ORCID, Le Chenadec Jerome8, Canestri Ana9, Morlat Philippe1011, Brunet-Cartier Cécile12, Sibiude Jeanne123, Peretti Delphine13, Chambrin Véronique14, Chabrol Amélie15, Bui Eida16, Simon-Toulza Caroline17, Marchand Lucie18, Paul Christelle18, Delmas Sandrine819, Avettand-Fenoel Véronique2620ORCID, Warszawski Josiane821, Delmas Sandrine, Capitant Catherine, Fournier Isabelle, Saillard Juliette, Marchand Lucie, Meyer Elie Azria Laurence, Rouveix Elisabeth, Goetghebuer Tessa, Barin Francis, Leroy Valériane, Arvieux Cédric, Blanche Stéphane, Dommergues Marc, Frange Pierre, Guerin Corinne, Marchand Lucie, Peytavin Gilles, Pollard Hélène, Plantier Jean-Christophe, Avettand Fenoel Véronique, Tubiana Roland, Diallo Alpha, Paul Christelle, Mandelbrot Laurent, Sibiude Jeanne, Meier Françoise, Floch Corinne, Tubiana Roland, Dommergues Marc, Blanc Christine, Canestri Ana, Selleret Lise, Morlat Philippe, Hessamfar Mojgan, Caldato Sabrina, Peretti Delphine, Houllier Marie, Fourcade Corinne, Chambrin Véronique, Letourneau Alexandra, Clech Laure, Chabrol Amélie, Canon Bérengère, Granier Michèle, Bui Eida, Dollfus Catherine, Simon-Toulza Caroline, Brazet Edith, Abbal Julie, Matheron Sophie, Bourgeois Moine Agnès, Arvieux Cédric, Pannier Emmanuelle, Marcou Valérie, Medus Marie, Wajszczak Ilona, Genet Philippe, Tordjeman Nathalie, Brault Dominique, Genet Philippe, Rami Agathe, Maraux Barbara, Bottero Julie, Benbara Amélie, Lachassine Eric, Rosenthal Eric, Naqvi Alissa, Bongain André, Monpoux Fabrice, Cotte Laurent, Huissoud Cyril, Labaune Jean-Marc, Dupon Michel, Roux Denis, Elleau Christophe, Duvivier Claudine, Driessen Marine, Frange Pierre, Avettand-Fenoel Véronique, Gardiennet Elise, Karmochkine Marina, Zucman David, Laperrelle Juliette, Brunet-Cartier Cécile, Winer Norbert, Reliquet Véronique, Mambert Marina, Levier Axel, Ladjal Hayette, Houel Cleìa, Lebas Barbara, Rahmoun Manal, Eliette Véronique, Resch Martine, Gardiennet Elise, Le Chenadec Jérôme, Arezes Elisa,
Affiliation:
1. Assistance Publique-Hôpitaux de Paris Hôpital Louis Mourier Service de Gynécologie-Obstétrique , F-92700 Colombes , France 2. Université Paris Cité , F-75006 Paris , France 3. INSERM, IAME , F-75018 Paris , France 4. Assistance Publique-Hôpitaux de Paris, Hôpital Pitié-Salpêtrière, Service Maladies infectieuses , F-75013 Paris , France 5. INSERM, Sorbonne Université, Institut Pierre Louis d’Epidémiologie et de Santé Publique (IPLESP UMRS 1136) , Paris , France 6. Laboratoire de microbiologie clinique, Groupe hospitalier Assistance Publique-Hôpitaux de Paris (APHP) Centre—Université Paris Cité, Hôpital Necker-Enfants Malades , F-75015 Paris , France 7. Assistance Publique-Hôpitaux de Paris, Laboratoire de Pharmaco-toxicologie, Hôpital Bichat , F-75018 Paris , France 8. INSERM CESP U1018, Université Paris-Saclay , Le Kremlin-Bicêtre , France 9. Assistance Publique-Hôpitaux de Paris, Hôpital Tenon, Service de Maladies Infectieuses , F-75020 Paris , France 10. Service de Médecine interne et Maladies infectieuses, Centre Hospitalier Universitaire de Bordeaux , Bordeaux , France 11. Université de Bordeaux , Bordeaux , France 12. Service de Maladies infectieuses, Centre Hospitalier Universitaire de Nantes , Nantes , France 13. Assistance Publique-Hôpitaux de Paris, Hôpital Kremlin-Bicêtre, Service de Maladies Infectieuses , Le Kremlin-Bicêtre , France 14. Assistance Publique-Hôpitaux de Paris, Hôpital Antoine Béclère, Service de Maladies Infectieuses , Clamart , France 15. Centre Hospitalier du Sud Francilien, Service de Maladies Infectieuses , Evry , France 16. Assistance Publique-Hôpitaux de Paris, Hôpital Trousseau, Service de Maladies Infectieuses , F-75012 Paris , France 17. Service de Médecine interne, Centre Hospitalier Universitaire de Toulouse , Toulouse , France 18. Agence Nationale de Recherches sur le sida et les hépatites virales ANRS|Maladies infectieuses émergentes , Paris , France 19. Institut National de la Santé et de la Recherche Médicale , SC10-US19, Villejuif , France 20. INSERM U1016, CNRS, UMR8104, Institut Cochin , Paris , France 21. Assistance Publique-Hôpitaux de Paris, Epidemiology and Public Health Service, Service, Hôpitaux Universitaires Paris-Saclay , Le Kremlin-Bicêtre , France
Abstract
Abstract
Objectives
Because NRTIs can have fetal toxicities, we evaluated a perinatal NRTI-sparing strategy to prevent perinatal HIV transmission. Our primary objective was to determine the proportion maintaining a viral load (VL) of <50 copies/mL up to delivery on darunavir/ritonavir monotherapy, without requiring treatment intensification.
Methods
In a one-arm, multicentre Phase 2 clinical trial, eligible patients in the first trimester of pregnancy on ART with plasma VL < 50 copies/mL received maintenance monotherapy with darunavir/ritonavir, 600/100 mg twice daily. VL was monitored monthly. ART was intensified in the case of VL > 50 copies/mL. Neonates received nevirapine prophylaxis for 14 days.
Results
Of 89 patients switching to darunavir/ritonavir monotherapy, 4 miscarried before 22 weeks’ gestation, 2 changed treatment for elevated liver enzymes without virological failure, and 83 were evaluable for the main outcome. Six had virological failure confirmed on a repeat sample (median VL = 193 copies/mL; range 78–644), including two before switching to monotherapy. In these six cases, ART was intensified with tenofovir disoproxil fumarate/emtricitabine. The success rate was 75/83, 90.4% (95% CI, 81.9%–95.7%) considering two patients with VL missing at delivery as failures, and 77/83, 92.8% (95% CI, 84.9%–97.3%) when considering them as successes since both had undetectable VL on darunavir/ritonavir throughout pregnancy. In ITT, the last available VL before delivery was <50 copies/mL in all of the patients. There was no case of perinatal HIV transmission.
Conclusions
Darunavir/ritonavir maintenance monotherapy required intensification in nearly 10% of cases. This limits its widespread use, thus other regimens should be evaluated in order to limit exposure to antiretrovirals, particularly NRTIs, during pregnancy.
Funder
French national agency Emerging infectious diseases
Publisher
Oxford University Press (OUP)
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology,Microbiology (medical)
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