Prevalence of predicted resistance to doravirine in HIV-1-positive patients after exposure to non-nucleoside reverse transcriptase inhibitors
•Doravirine (DOR) resistance is uncommon among non-nucleoside reverse transcriptase inhibitor (NNRTI)-experienced patients.•Complete DOR resistance in NNRTI-experienced patients is mainly related to Y188L mutation.•Previous efavirenz and etravirine use are associated with detection of DOR resistance...
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| Veröffentlicht in: | International journal of antimicrobial agents 2019-04, Vol.53 (4), p.515-519 |
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| creator | Sterrantino, Gaetana Borghi, Vanni Callegaro, Anna Paola Bruzzone, Bianca Saladini, Francesco Maggiolo, Franco Maffongelli, Gaetano Andreoni, Massimo De Gennaro, Michele Gianotti, Nicola Bagnarelli, Patrizia Vergori, Alessandra Antinori, Andrea Zazzi, Maurizio Zaccarelli, Mauro |
| description | •Doravirine (DOR) resistance is uncommon among non-nucleoside reverse transcriptase inhibitor (NNRTI)-experienced patients.•Complete DOR resistance in NNRTI-experienced patients is mainly related to Y188L mutation.•Previous efavirenz and etravirine use are associated with detection of DOR resistance.•Previous rilpivirine use is associated with a lower probability of DOR resistance.
This study investigated the prevalence of doravirine (DOR) resistance mutations in non-nucleoside reverse transcriptase inhibitor (NNRTI)-experienced patients. DOR resistance was assessed in samples from NNRTI-experienced patients who underwent genotypic testing for virological failure from the Antiretroviral Response Cohort Analysis (ARCA) database. Intermediate DOR resistance was defined as detection of any of V106A/M, Y188C/H, V108I, and K103N+P225H. High-level DOR resistance was defined as detection of any of Y188L, M230L, G190E, V106A/M+F227L, and V106A/M+L234I. Overall, 6893 patients were included in the study: 64.2% had experienced efavirenz (EFV), 54.4% nevirapine (NVP), 6.8% etravirine (ETR), 7.7% rilpivirine (RPV) and 0.7% delavirdine. Among NNRTI-experienced patients, 12.7% and 6.1% of subjects had intermediate and high-level DOR resistance, respectively. The most common DOR resistance mutation was Y188L. In multivariable analysis, previous EFV use (OR = 1.52, 95% CI 1.15–2.02) and ETR use (OR = 1.91, 95% CI 1.34–2.73) were associated with detection of high-level DOR resistance, whilst RPV use was associated with a lower probability of high-level DOR resistance (OR = 0.39, 95% CI 0.22–0.71). Moreover, EFV use (OR = 1.76, 95% CI 1.19–2.58) and ETR use (OR = 1.72, 95% CI 1.10–2.68) were associated with detection of the Y188L mutation, whereas RPV use was not (OR = 0.16, 95% CI 0.05–0.50). In Italy, DOR resistance is uncommon among NNRTI-experienced patients, confirming a distinguishing resistance pattern within NNRTIs. However, previous EFV and ETR experience poses a higher risk of DOR resistance. These results support the use of DOR in NNRTI-experienced patients. |
| doi_str_mv | 10.1016/j.ijantimicag.2019.02.007 |
| format | Article |
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This study investigated the prevalence of doravirine (DOR) resistance mutations in non-nucleoside reverse transcriptase inhibitor (NNRTI)-experienced patients. DOR resistance was assessed in samples from NNRTI-experienced patients who underwent genotypic testing for virological failure from the Antiretroviral Response Cohort Analysis (ARCA) database. Intermediate DOR resistance was defined as detection of any of V106A/M, Y188C/H, V108I, and K103N+P225H. High-level DOR resistance was defined as detection of any of Y188L, M230L, G190E, V106A/M+F227L, and V106A/M+L234I. Overall, 6893 patients were included in the study: 64.2% had experienced efavirenz (EFV), 54.4% nevirapine (NVP), 6.8% etravirine (ETR), 7.7% rilpivirine (RPV) and 0.7% delavirdine. Among NNRTI-experienced patients, 12.7% and 6.1% of subjects had intermediate and high-level DOR resistance, respectively. The most common DOR resistance mutation was Y188L. In multivariable analysis, previous EFV use (OR = 1.52, 95% CI 1.15–2.02) and ETR use (OR = 1.91, 95% CI 1.34–2.73) were associated with detection of high-level DOR resistance, whilst RPV use was associated with a lower probability of high-level DOR resistance (OR = 0.39, 95% CI 0.22–0.71). Moreover, EFV use (OR = 1.76, 95% CI 1.19–2.58) and ETR use (OR = 1.72, 95% CI 1.10–2.68) were associated with detection of the Y188L mutation, whereas RPV use was not (OR = 0.16, 95% CI 0.05–0.50). In Italy, DOR resistance is uncommon among NNRTI-experienced patients, confirming a distinguishing resistance pattern within NNRTIs. However, previous EFV and ETR experience poses a higher risk of DOR resistance. These results support the use of DOR in NNRTI-experienced patients.</description><identifier>ISSN: 0924-8579</identifier><identifier>EISSN: 1872-7913</identifier><identifier>DOI: 10.1016/j.ijantimicag.2019.02.007</identifier><identifier>PMID: 30769200</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Antiretroviral therapy ; Doravirine ; HIV-1 ; NNRTI ; Predicted resistance ; Treatment-experienced subjects</subject><ispartof>International journal of antimicrobial agents, 2019-04, Vol.53 (4), p.515-519</ispartof><rights>2019 Elsevier B.V. and International Society of Chemotherapy</rights><rights>Copyright © 2019 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c377t-f7760c0095989d329e1bfe182d2462bc3f229c5e78fbc0357387537c9467b3983</citedby><cites>FETCH-LOGICAL-c377t-f7760c0095989d329e1bfe182d2462bc3f229c5e78fbc0357387537c9467b3983</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0924857919300305$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30769200$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sterrantino, Gaetana</creatorcontrib><creatorcontrib>Borghi, Vanni</creatorcontrib><creatorcontrib>Callegaro, Anna Paola</creatorcontrib><creatorcontrib>Bruzzone, Bianca</creatorcontrib><creatorcontrib>Saladini, Francesco</creatorcontrib><creatorcontrib>Maggiolo, Franco</creatorcontrib><creatorcontrib>Maffongelli, Gaetano</creatorcontrib><creatorcontrib>Andreoni, Massimo</creatorcontrib><creatorcontrib>De Gennaro, Michele</creatorcontrib><creatorcontrib>Gianotti, Nicola</creatorcontrib><creatorcontrib>Bagnarelli, Patrizia</creatorcontrib><creatorcontrib>Vergori, Alessandra</creatorcontrib><creatorcontrib>Antinori, Andrea</creatorcontrib><creatorcontrib>Zazzi, Maurizio</creatorcontrib><creatorcontrib>Zaccarelli, Mauro</creatorcontrib><creatorcontrib>ARCA Study Group</creatorcontrib><title>Prevalence of predicted resistance to doravirine in HIV-1-positive patients after exposure to non-nucleoside reverse transcriptase inhibitors</title><title>International journal of antimicrobial agents</title><addtitle>Int J Antimicrob Agents</addtitle><description>•Doravirine (DOR) resistance is uncommon among non-nucleoside reverse transcriptase inhibitor (NNRTI)-experienced patients.•Complete DOR resistance in NNRTI-experienced patients is mainly related to Y188L mutation.•Previous efavirenz and etravirine use are associated with detection of DOR resistance.•Previous rilpivirine use is associated with a lower probability of DOR resistance.
This study investigated the prevalence of doravirine (DOR) resistance mutations in non-nucleoside reverse transcriptase inhibitor (NNRTI)-experienced patients. DOR resistance was assessed in samples from NNRTI-experienced patients who underwent genotypic testing for virological failure from the Antiretroviral Response Cohort Analysis (ARCA) database. Intermediate DOR resistance was defined as detection of any of V106A/M, Y188C/H, V108I, and K103N+P225H. High-level DOR resistance was defined as detection of any of Y188L, M230L, G190E, V106A/M+F227L, and V106A/M+L234I. Overall, 6893 patients were included in the study: 64.2% had experienced efavirenz (EFV), 54.4% nevirapine (NVP), 6.8% etravirine (ETR), 7.7% rilpivirine (RPV) and 0.7% delavirdine. Among NNRTI-experienced patients, 12.7% and 6.1% of subjects had intermediate and high-level DOR resistance, respectively. The most common DOR resistance mutation was Y188L. In multivariable analysis, previous EFV use (OR = 1.52, 95% CI 1.15–2.02) and ETR use (OR = 1.91, 95% CI 1.34–2.73) were associated with detection of high-level DOR resistance, whilst RPV use was associated with a lower probability of high-level DOR resistance (OR = 0.39, 95% CI 0.22–0.71). Moreover, EFV use (OR = 1.76, 95% CI 1.19–2.58) and ETR use (OR = 1.72, 95% CI 1.10–2.68) were associated with detection of the Y188L mutation, whereas RPV use was not (OR = 0.16, 95% CI 0.05–0.50). In Italy, DOR resistance is uncommon among NNRTI-experienced patients, confirming a distinguishing resistance pattern within NNRTIs. However, previous EFV and ETR experience poses a higher risk of DOR resistance. These results support the use of DOR in NNRTI-experienced patients.</description><subject>Antiretroviral therapy</subject><subject>Doravirine</subject><subject>HIV-1</subject><subject>NNRTI</subject><subject>Predicted resistance</subject><subject>Treatment-experienced subjects</subject><issn>0924-8579</issn><issn>1872-7913</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNqNkcGO1SAUhonRONfRVzB156b1AG0pS3OjziST6ELdEkpP9dz0QgXa6EP4zrbe0bh0RcL5_v8EPsZecKg48PbVqaKT9ZnO5OyXSgDXFYgKQD1gB94pUSrN5UN2AC3qsmuUvmJPUjoB8EbWzWN2JUG1WgAc2M8PEVc7oXdYhLGYIw7kMg5FxEQp2_0-h2II0a4UyWNBvri5_Vzycg6JMq1YzDYT-pwKO2aMBX7fJkv8nfPBl35xE27sgFvpijFtk2h9cpHmbNPe-JV6yiGmp-zRaKeEz-7Pa_bp7ZuPx5vy7v272-Pru9JJpXI5KtWCA9CN7vQghUbej8g7MYi6Fb2ToxDaNai6sXcgGyU71UjldN2qXupOXrOXl945hm8LpmzOlBxOk_UYlmQE141oaujEhuoL6mJIKeJo5khnG38YDma3YU7mHxtmt2FAmM3Gln1-v2bpzzj8Tf75_g04XgDcHrsSRpMc7S4GiuiyGQL9x5pf-XqkPg</recordid><startdate>20190401</startdate><enddate>20190401</enddate><creator>Sterrantino, Gaetana</creator><creator>Borghi, Vanni</creator><creator>Callegaro, Anna Paola</creator><creator>Bruzzone, Bianca</creator><creator>Saladini, Francesco</creator><creator>Maggiolo, Franco</creator><creator>Maffongelli, Gaetano</creator><creator>Andreoni, Massimo</creator><creator>De Gennaro, Michele</creator><creator>Gianotti, Nicola</creator><creator>Bagnarelli, Patrizia</creator><creator>Vergori, Alessandra</creator><creator>Antinori, Andrea</creator><creator>Zazzi, Maurizio</creator><creator>Zaccarelli, Mauro</creator><general>Elsevier B.V</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20190401</creationdate><title>Prevalence of predicted resistance to doravirine in HIV-1-positive patients after exposure to non-nucleoside reverse transcriptase inhibitors</title><author>Sterrantino, Gaetana ; Borghi, Vanni ; Callegaro, Anna Paola ; Bruzzone, Bianca ; Saladini, Francesco ; Maggiolo, Franco ; Maffongelli, Gaetano ; Andreoni, Massimo ; De Gennaro, Michele ; Gianotti, Nicola ; Bagnarelli, Patrizia ; Vergori, Alessandra ; Antinori, Andrea ; Zazzi, Maurizio ; Zaccarelli, Mauro</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c377t-f7760c0095989d329e1bfe182d2462bc3f229c5e78fbc0357387537c9467b3983</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Antiretroviral therapy</topic><topic>Doravirine</topic><topic>HIV-1</topic><topic>NNRTI</topic><topic>Predicted resistance</topic><topic>Treatment-experienced subjects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sterrantino, Gaetana</creatorcontrib><creatorcontrib>Borghi, Vanni</creatorcontrib><creatorcontrib>Callegaro, Anna Paola</creatorcontrib><creatorcontrib>Bruzzone, Bianca</creatorcontrib><creatorcontrib>Saladini, Francesco</creatorcontrib><creatorcontrib>Maggiolo, Franco</creatorcontrib><creatorcontrib>Maffongelli, Gaetano</creatorcontrib><creatorcontrib>Andreoni, Massimo</creatorcontrib><creatorcontrib>De Gennaro, Michele</creatorcontrib><creatorcontrib>Gianotti, Nicola</creatorcontrib><creatorcontrib>Bagnarelli, Patrizia</creatorcontrib><creatorcontrib>Vergori, Alessandra</creatorcontrib><creatorcontrib>Antinori, Andrea</creatorcontrib><creatorcontrib>Zazzi, Maurizio</creatorcontrib><creatorcontrib>Zaccarelli, Mauro</creatorcontrib><creatorcontrib>ARCA Study Group</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>International journal of antimicrobial agents</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sterrantino, Gaetana</au><au>Borghi, Vanni</au><au>Callegaro, Anna Paola</au><au>Bruzzone, Bianca</au><au>Saladini, Francesco</au><au>Maggiolo, Franco</au><au>Maffongelli, Gaetano</au><au>Andreoni, Massimo</au><au>De Gennaro, Michele</au><au>Gianotti, Nicola</au><au>Bagnarelli, Patrizia</au><au>Vergori, Alessandra</au><au>Antinori, Andrea</au><au>Zazzi, Maurizio</au><au>Zaccarelli, Mauro</au><aucorp>ARCA Study Group</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Prevalence of predicted resistance to doravirine in HIV-1-positive patients after exposure to non-nucleoside reverse transcriptase inhibitors</atitle><jtitle>International journal of antimicrobial agents</jtitle><addtitle>Int J Antimicrob Agents</addtitle><date>2019-04-01</date><risdate>2019</risdate><volume>53</volume><issue>4</issue><spage>515</spage><epage>519</epage><pages>515-519</pages><issn>0924-8579</issn><eissn>1872-7913</eissn><abstract>•Doravirine (DOR) resistance is uncommon among non-nucleoside reverse transcriptase inhibitor (NNRTI)-experienced patients.•Complete DOR resistance in NNRTI-experienced patients is mainly related to Y188L mutation.•Previous efavirenz and etravirine use are associated with detection of DOR resistance.•Previous rilpivirine use is associated with a lower probability of DOR resistance.
This study investigated the prevalence of doravirine (DOR) resistance mutations in non-nucleoside reverse transcriptase inhibitor (NNRTI)-experienced patients. DOR resistance was assessed in samples from NNRTI-experienced patients who underwent genotypic testing for virological failure from the Antiretroviral Response Cohort Analysis (ARCA) database. Intermediate DOR resistance was defined as detection of any of V106A/M, Y188C/H, V108I, and K103N+P225H. High-level DOR resistance was defined as detection of any of Y188L, M230L, G190E, V106A/M+F227L, and V106A/M+L234I. Overall, 6893 patients were included in the study: 64.2% had experienced efavirenz (EFV), 54.4% nevirapine (NVP), 6.8% etravirine (ETR), 7.7% rilpivirine (RPV) and 0.7% delavirdine. Among NNRTI-experienced patients, 12.7% and 6.1% of subjects had intermediate and high-level DOR resistance, respectively. The most common DOR resistance mutation was Y188L. In multivariable analysis, previous EFV use (OR = 1.52, 95% CI 1.15–2.02) and ETR use (OR = 1.91, 95% CI 1.34–2.73) were associated with detection of high-level DOR resistance, whilst RPV use was associated with a lower probability of high-level DOR resistance (OR = 0.39, 95% CI 0.22–0.71). Moreover, EFV use (OR = 1.76, 95% CI 1.19–2.58) and ETR use (OR = 1.72, 95% CI 1.10–2.68) were associated with detection of the Y188L mutation, whereas RPV use was not (OR = 0.16, 95% CI 0.05–0.50). In Italy, DOR resistance is uncommon among NNRTI-experienced patients, confirming a distinguishing resistance pattern within NNRTIs. However, previous EFV and ETR experience poses a higher risk of DOR resistance. These results support the use of DOR in NNRTI-experienced patients.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>30769200</pmid><doi>10.1016/j.ijantimicag.2019.02.007</doi><tpages>5</tpages></addata></record> |
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| subjects | Antiretroviral therapy Doravirine HIV-1 NNRTI Predicted resistance Treatment-experienced subjects |
| title | Prevalence of predicted resistance to doravirine in HIV-1-positive patients after exposure to non-nucleoside reverse transcriptase inhibitors |
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