Rare occurrence of doravirine resistance-associated mutations in HIV-1-infected treatment-naive patients

Cathia Soulie, Maria Mercedes Santoro, Charlotte Charpentier, Alexandre Storto, Dimitrios Paraskevis, Domenico Di Carlo, William Gennari, Gaetana Sterrantino, Maurizio Zazzi, Carlo Federico Perno, Vincent Calvez, Diane Descamps, Francesca Ceccherini-Silberstein, Anne-Geneviève Marcelin

Research output: Contribution to journalArticle

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.

Original languageEnglish
JournalThe Journal of antimicrobial chemotherapy
DOIs
Publication statusE-pub ahead of print - Nov 23 2018

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HIV-1
Mutation
efavirenz
Rilpivirine
etravirine
Therapeutics
Nevirapine
Ritonavir
Greece
Drug Resistance
Italy
France
Viruses

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Rare occurrence of doravirine resistance-associated mutations in HIV-1-infected treatment-naive patients. / Soulie, Cathia; Santoro, Maria Mercedes; Charpentier, Charlotte; Storto, Alexandre; Paraskevis, Dimitrios; Di Carlo, Domenico; Gennari, William; Sterrantino, Gaetana; Zazzi, Maurizio; Perno, Carlo Federico; Calvez, Vincent; Descamps, Diane; Ceccherini-Silberstein, Francesca; Marcelin, Anne-Geneviève.

In: The Journal of antimicrobial chemotherapy, 23.11.2018.

Research output: Contribution to journalArticle

Soulie, C, Santoro, MM, Charpentier, C, Storto, A, Paraskevis, D, Di Carlo, D, Gennari, W, Sterrantino, G, Zazzi, M, Perno, CF, Calvez, V, Descamps, D, Ceccherini-Silberstein, F & Marcelin, A-G 2018, 'Rare occurrence of doravirine resistance-associated mutations in HIV-1-infected treatment-naive patients', The Journal of antimicrobial chemotherapy. https://doi.org/10.1093/jac/dky464
Soulie, Cathia ; Santoro, Maria Mercedes ; Charpentier, Charlotte ; Storto, Alexandre ; Paraskevis, Dimitrios ; Di Carlo, Domenico ; Gennari, William ; Sterrantino, Gaetana ; Zazzi, Maurizio ; Perno, Carlo Federico ; Calvez, Vincent ; Descamps, Diane ; Ceccherini-Silberstein, Francesca ; Marcelin, Anne-Geneviève. / Rare occurrence of doravirine resistance-associated mutations in HIV-1-infected treatment-naive patients. In: The Journal of antimicrobial chemotherapy. 2018.
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title = "Rare occurrence of doravirine resistance-associated mutations in HIV-1-infected treatment-naive patients",
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.",
author = "Cathia Soulie and Santoro, {Maria Mercedes} and Charlotte Charpentier and Alexandre Storto and Dimitrios Paraskevis and {Di Carlo}, Domenico and William Gennari and Gaetana Sterrantino and Maurizio Zazzi and Perno, {Carlo Federico} and Vincent Calvez and Diane Descamps and Francesca Ceccherini-Silberstein and Anne-Genevi{\`e}ve Marcelin",
year = "2018",
month = "11",
day = "23",
doi = "10.1093/jac/dky464",
language = "English",
journal = "Journal of Antimicrobial Chemotherapy",
issn = "0305-7453",
publisher = "Oxford University Press",

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TY - JOUR

T1 - Rare occurrence of doravirine resistance-associated mutations in HIV-1-infected treatment-naive patients

AU - Soulie, Cathia

AU - Santoro, Maria Mercedes

AU - Charpentier, Charlotte

AU - Storto, Alexandre

AU - Paraskevis, Dimitrios

AU - Di Carlo, Domenico

AU - Gennari, William

AU - Sterrantino, Gaetana

AU - Zazzi, Maurizio

AU - Perno, Carlo Federico

AU - Calvez, Vincent

AU - Descamps, Diane

AU - Ceccherini-Silberstein, Francesca

AU - Marcelin, Anne-Geneviève

PY - 2018/11/23

Y1 - 2018/11/23

N2 - 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.

AB - 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.

U2 - 10.1093/jac/dky464

DO - 10.1093/jac/dky464

M3 - Article

C2 - 30476106

JO - Journal of Antimicrobial Chemotherapy

JF - Journal of Antimicrobial Chemotherapy

SN - 0305-7453

ER -