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 language | English |
|---|---|
| Journal | The Journal of antimicrobial chemotherapy |
| DOIs | |
| Publication status | E-pub ahead of print - Nov 23 2018 |
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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 journal › Article
}
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 -