Cathia Soulie1, Maria Mercedes Santoro2, Charlotte Charpentier3, Alexandre Storto3, Dimitrios Paraskevis4, Domenico Di Carlo5, William Gennari6, Gaetana Sterrantino7, Maurizio Zazzi8, Carlo Federico Perno9,10, Vincent Calvez1, Diane Descamps3, Francesca Ceccherini-Silberstein2, Anne-Geneviève Marcelin1. 1. Sorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), AP-HP, Hôpital Pitié-Salpêtrière, Laboratoire de virologie, Paris, France. 2. University of Rome 'Tor Vergata', Department of Experimental Medicine and Surgery, Rome, Italy. 3. IAME, UMR 1137, INSERM, Université Paris Diderot, Sorbonne Paris Cité, AP-HP, Laboratoire de Virologie, Hôpital Bichat, AP-HP, Paris, France. 4. Department of Hygiene Epidemiology and Medical Statistics, Medical School, National and Kapodistrian University of Athens, Athens, Greece. 5. University of Milan, Paediatric Clinical Research Center 'Romeo and Enrica Invernizzi', Milan, Italy. 6. University Hospital Polyclinic, Microbiology and Virology Unit, Modena, Italy. 7. 'Careggi' Hospital, Division of Infectious Diseases, Florence, Italy. 8. University of Siena, Department of Medical Biotechnology, Siena, Italy. 9. National Institute for Infectious Diseases L. Spallanzani, IRCCS, Antiretroviral Therapy Monitoring Unit, Rome, Italy. 10. Department of Oncology, University of Milan, Milan, Italy.
Abstract
BACKGROUND: Doravirine is a novel HIV-1 NNRTI recently shown to be non-inferior to both darunavir/ritonavir and efavirenz in combination therapy with two NRTIs in treatment-naive patients. Doravirine has an in vitro resistance profile that is distinct from other NNRTIs and retains activity against viruses containing the most frequently transmitted NNRTI mutations. OBJECTIVES: The aim of this study was to examine the prevalence of doravirine resistance-associated mutations in HIV-1-infected treatment-naive patients in Europe. METHODS: From 2010 to 2016, 9764 treatment-naive patients were tested for NNRTI antiretroviral drug resistance by bulk sequencing in Greece, Italy and France. We studied the prevalence of doravirine resistance-associated mutations previously identified in vitro: V106A/M, V108I, Y188L, V190S, H221Y, F227C/L/V, M230I/L, L234I, P236L, Y318F and K103N/Y181C. RESULTS: Among 9764 sequences, 53.0% and 47.0% of patients had B and non-B subtypes, respectively. Overall, the presence of at least one doravirine resistance-associated mutation (n = 137; 1.4%) or the K103N/Y181C mutations (n = 5; 0.05%) was very rare. The most prevalent mutations were V108I (n = 62; 0.6%), Y188L (n = 18; 0.2%), H221Y (n = 18; 0.2%) and Y318F (n = 23; 0.2%). The frequency of doravirine resistance-associated mutations was similar between B and non-B subtypes. In comparison, the prevalence of rilpivirine, etravirine, nevirapine and efavirenz resistance was higher whatever algorithm was used (ANRS: 8.5%, 8.1%, 8.3% and 3.9%, respectively; Stanford: 9.9%, 10.0%, 7.5% and 9.4%, respectively). CONCLUSIONS: The prevalence of doravirine resistance-associated mutations is very low in antiretroviral-naive patients. These results are very reassuring for doravirine use in naive patients.
BACKGROUND:Doravirine is a novel HIV-1 NNRTI recently shown to be non-inferior to both darunavir/ritonavir and efavirenz in combination therapy with two NRTIs in treatment-naive patients. Doravirine has an in vitro resistance profile that is distinct from other NNRTIs and retains activity against viruses containing the most frequently transmitted NNRTI mutations. OBJECTIVES: The aim of this study was to examine the prevalence of doravirine resistance-associated mutations in HIV-1-infected treatment-naive patients in Europe. METHODS: From 2010 to 2016, 9764 treatment-naive patients were tested for NNRTI antiretroviral drug resistance by bulk sequencing in Greece, Italy and France. We studied the prevalence of doravirine resistance-associated mutations previously identified in vitro: V106A/M, V108I, Y188L, V190S, H221Y, F227C/L/V, M230I/L, L234I, P236L, Y318F and K103N/Y181C. RESULTS: Among 9764 sequences, 53.0% and 47.0% of patients had B and non-B subtypes, respectively. Overall, the presence of at least one doravirine resistance-associated mutation (n = 137; 1.4%) or the K103N/Y181C mutations (n = 5; 0.05%) was very rare. The most prevalent mutations were V108I (n = 62; 0.6%), Y188L (n = 18; 0.2%), H221Y (n = 18; 0.2%) and Y318F (n = 23; 0.2%). The frequency of doravirine resistance-associated mutations was similar between B and non-B subtypes. In comparison, the prevalence of rilpivirine, etravirine, nevirapine and efavirenz resistance was higher whatever algorithm was used (ANRS: 8.5%, 8.1%, 8.3% and 3.9%, respectively; Stanford: 9.9%, 10.0%, 7.5% and 9.4%, respectively). CONCLUSIONS: The prevalence of doravirine resistance-associated mutations is very low in antiretroviral-naive patients. These results are very reassuring for doravirine use in naive patients.
Authors: Kim Steegen; Michelle Moorhouse; Annemarie Mj Wensing; Willem Df Venter; Lucia Hans Journal: J Int AIDS Soc Date: 2021-05 Impact factor: 5.396
Authors: Maria Mazzitelli; Melania Degli Antoni; Francesco Castelli; Diego Ripamonti; Gianluca Zuglian; Giuseppe Lapadula; Massimiliano Fabbiani; Alice Ferraresi; Cristina Putaggio; Anna Maria Cattelan; Eugenia Quiros-Roldan Journal: Medicine (Baltimore) Date: 2022-07-29 Impact factor: 1.817