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Virological response and resistance profile in highly treatment‐experienced HIV‐1‐infected patients switching to dolutegravir plus boosted darunavir in clinical practice
Objectives We evaluated the virological response and resistance profile in combined antiretroviral therapy (cART)‐experienced HIV‐1‐infected patients starting a dual therapy with dolutegravir (DTG) and boosted darunavir (bDRV) for the first time. Methods Survival analyses were used to evaluate virol...
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| Published in: | HIV medicine 2021-07, Vol.22 (6), p.519-525 |
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| container_title | HIV medicine |
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| creator | Armenia, Daniele Bouba, Yagai Gagliardini, Roberta Fabeni, Lavinia Borghi, Vanni Berno, Giulia Vergori, Alessandra Cicalini, Stefania Mussini, Cristina Antinori, Andrea Ceccherini‐Silberstein, Francesca Perno, Carlo Federico Santoro, Maria Mercedes |
| description | Objectives
We evaluated the virological response and resistance profile in combined antiretroviral therapy (cART)‐experienced HIV‐1‐infected patients starting a dual therapy with dolutegravir (DTG) and boosted darunavir (bDRV) for the first time.
Methods
Survival analyses were used to evaluate virological success (VS) and virological rebound (VR) in viraemic and virologically suppressed patients, respectively. Major resistance mutations (MRMs) and genotypic susceptibility score (GSS) were evaluated at baseline and after switch.
Results
Overall, 130 patients [62 (47.7%) viraemic; 68 (52.3%) virologically suppressed] were retrospectively analysed. At the moment of switch, 81.5% accumulated one or more MRM [protease inhibitor (PI), 35.7%; nucleoside(t)ide reverse transcriptase inhibitor (NRTI), 77.5%; non‐NRTI, 69.0%; integrase inhibitor (INI), 10.1%), but 77.7% harboured strains fully susceptible to DTG + bDRV. In viraemic patients, the overall probability of VS by 12 months of treatment was 91.7%. In virologically suppressed patients, the overall probability of VR was 10.5% by 24 months after therapy start. Patients with previous time under virological suppression ≤ 6 months showed a higher VR probability compared with others (37.5% vs. 6.7%, P |
| doi_str_mv | 10.1111/hiv.13062 |
| format | article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2480265596</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2480265596</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3882-e3be0169fc6891dad95e21d15cce9c8baca3a0dfd93e8db8d3cf523b33d4b0313</originalsourceid><addsrcrecordid>eNp1kc9uFSEUxonR2Fpd-AKGxI0upuXPDMLSNGqbNHGj3RIGztxLw4URmLZ35yP4Jr6TTyL33urCRBLC4eOXjwMfQi8pOaVtnK397SnlRLBH6Jj2QnaUKf54X_cdE4IdoWel3BBC33FFnqIjzntJiOqP0c9rn1NIK29NwBnKnGIBbKLbbXypJlrAc06TD4B9xGu_WoctrhlM3UCsv77_gPsZsocGOnxxed0U2qaPE9japNnUdlgLLne-2rWPK1wTdiksFVbZ3PqM57AUPKZUdrwzeYl7uV1ng4_71uZsbPUWnqMnkwkFXjysJ-jrxw9fzi-6q8-fLs_fX3WWS8k64CMQKtRkhVTUGacGYNTRwVpQVo7GGm6Im5ziIN0oHbfTwPjIuetHwik_QW8Ovu3t3xYoVW98sRCCiZCWoln7QCaGQYmGvv4HvUlLjq07zQYuJOVU7AzfHiibUykZJj1nvzF5qynRuxR1S1HvU2zsqwfHZdyA-0v-ia0BZwfgrsWy_b-TbnkcLH8Diriuuw</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2536813161</pqid></control><display><type>article</type><title>Virological response and resistance profile in highly treatment‐experienced HIV‐1‐infected patients switching to dolutegravir plus boosted darunavir in clinical practice</title><source>Wiley-Blackwell Read & Publish Collection</source><creator>Armenia, Daniele ; Bouba, Yagai ; Gagliardini, Roberta ; Fabeni, Lavinia ; Borghi, Vanni ; Berno, Giulia ; Vergori, Alessandra ; Cicalini, Stefania ; Mussini, Cristina ; Antinori, Andrea ; Ceccherini‐Silberstein, Francesca ; Perno, Carlo Federico ; Santoro, Maria Mercedes</creator><creatorcontrib>Armenia, Daniele ; Bouba, Yagai ; Gagliardini, Roberta ; Fabeni, Lavinia ; Borghi, Vanni ; Berno, Giulia ; Vergori, Alessandra ; Cicalini, Stefania ; Mussini, Cristina ; Antinori, Andrea ; Ceccherini‐Silberstein, Francesca ; Perno, Carlo Federico ; Santoro, Maria Mercedes</creatorcontrib><description>Objectives
We evaluated the virological response and resistance profile in combined antiretroviral therapy (cART)‐experienced HIV‐1‐infected patients starting a dual therapy with dolutegravir (DTG) and boosted darunavir (bDRV) for the first time.
Methods
Survival analyses were used to evaluate virological success (VS) and virological rebound (VR) in viraemic and virologically suppressed patients, respectively. Major resistance mutations (MRMs) and genotypic susceptibility score (GSS) were evaluated at baseline and after switch.
Results
Overall, 130 patients [62 (47.7%) viraemic; 68 (52.3%) virologically suppressed] were retrospectively analysed. At the moment of switch, 81.5% accumulated one or more MRM [protease inhibitor (PI), 35.7%; nucleoside(t)ide reverse transcriptase inhibitor (NRTI), 77.5%; non‐NRTI, 69.0%; integrase inhibitor (INI), 10.1%), but 77.7% harboured strains fully susceptible to DTG + bDRV. In viraemic patients, the overall probability of VS by 12 months of treatment was 91.7%. In virologically suppressed patients, the overall probability of VR was 10.5% by 24 months after therapy start. Patients with previous time under virological suppression ≤ 6 months showed a higher VR probability compared with others (37.5% vs. 6.7%, P < 0.002). Among 13 non‐responding patients for whom a genotypic resistance test result at failure was available, only two (15.4%) accumulated further resistance in integrase (Y143C/H/R; S147G and N155H) and protease (V32I, L33F, I54L).
Conclusions
In highly treatment‐experienced patients, the use of dual therapy based on DTG + bDRV appears to be a very good regimen for switch therapy, with a high rate of virological control in both viraemic and virologically suppressed patients. Among non‐responding patients, the selection of further resistance is a rare event.</description><identifier>ISSN: 1464-2662</identifier><identifier>EISSN: 1468-1293</identifier><identifier>DOI: 10.1111/hiv.13062</identifier><identifier>PMID: 33480094</identifier><language>eng</language><publisher>England: Wiley Subscription Services, Inc</publisher><subject>Anti-HIV Agents - pharmacology ; Anti-HIV Agents - therapeutic use ; Antiretroviral agents ; Antiretroviral therapy ; Darunavir ; dolutegravir ; drug resistance ; dual therapy ; genotypic susceptibility score ; Heterocyclic Compounds, 3-Ring ; HIV ; HIV Infections - drug therapy ; HIV-1 - genetics ; HIV‐1 ; Human immunodeficiency virus ; Humans ; Integrase ; Mutation ; Oxazines ; Patients ; Piperazines ; Protease ; Protease inhibitors ; Proteinase inhibitors ; Pyridones ; Retrospective Studies ; RNA-directed DNA polymerase ; Therapy ; Viral Load ; virological response</subject><ispartof>HIV medicine, 2021-07, Vol.22 (6), p.519-525</ispartof><rights>2021 British HIV Association</rights><rights>2021 British HIV Association.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3882-e3be0169fc6891dad95e21d15cce9c8baca3a0dfd93e8db8d3cf523b33d4b0313</citedby><cites>FETCH-LOGICAL-c3882-e3be0169fc6891dad95e21d15cce9c8baca3a0dfd93e8db8d3cf523b33d4b0313</cites><orcidid>0000-0001-6944-0686 ; 0000-0002-6228-1114 ; 0000-0002-3406-7014</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33480094$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Armenia, Daniele</creatorcontrib><creatorcontrib>Bouba, Yagai</creatorcontrib><creatorcontrib>Gagliardini, Roberta</creatorcontrib><creatorcontrib>Fabeni, Lavinia</creatorcontrib><creatorcontrib>Borghi, Vanni</creatorcontrib><creatorcontrib>Berno, Giulia</creatorcontrib><creatorcontrib>Vergori, Alessandra</creatorcontrib><creatorcontrib>Cicalini, Stefania</creatorcontrib><creatorcontrib>Mussini, Cristina</creatorcontrib><creatorcontrib>Antinori, Andrea</creatorcontrib><creatorcontrib>Ceccherini‐Silberstein, Francesca</creatorcontrib><creatorcontrib>Perno, Carlo Federico</creatorcontrib><creatorcontrib>Santoro, Maria Mercedes</creatorcontrib><title>Virological response and resistance profile in highly treatment‐experienced HIV‐1‐infected patients switching to dolutegravir plus boosted darunavir in clinical practice</title><title>HIV medicine</title><addtitle>HIV Med</addtitle><description>Objectives
We evaluated the virological response and resistance profile in combined antiretroviral therapy (cART)‐experienced HIV‐1‐infected patients starting a dual therapy with dolutegravir (DTG) and boosted darunavir (bDRV) for the first time.
Methods
Survival analyses were used to evaluate virological success (VS) and virological rebound (VR) in viraemic and virologically suppressed patients, respectively. Major resistance mutations (MRMs) and genotypic susceptibility score (GSS) were evaluated at baseline and after switch.
Results
Overall, 130 patients [62 (47.7%) viraemic; 68 (52.3%) virologically suppressed] were retrospectively analysed. At the moment of switch, 81.5% accumulated one or more MRM [protease inhibitor (PI), 35.7%; nucleoside(t)ide reverse transcriptase inhibitor (NRTI), 77.5%; non‐NRTI, 69.0%; integrase inhibitor (INI), 10.1%), but 77.7% harboured strains fully susceptible to DTG + bDRV. In viraemic patients, the overall probability of VS by 12 months of treatment was 91.7%. In virologically suppressed patients, the overall probability of VR was 10.5% by 24 months after therapy start. Patients with previous time under virological suppression ≤ 6 months showed a higher VR probability compared with others (37.5% vs. 6.7%, P < 0.002). Among 13 non‐responding patients for whom a genotypic resistance test result at failure was available, only two (15.4%) accumulated further resistance in integrase (Y143C/H/R; S147G and N155H) and protease (V32I, L33F, I54L).
Conclusions
In highly treatment‐experienced patients, the use of dual therapy based on DTG + bDRV appears to be a very good regimen for switch therapy, with a high rate of virological control in both viraemic and virologically suppressed patients. Among non‐responding patients, the selection of further resistance is a rare event.</description><subject>Anti-HIV Agents - pharmacology</subject><subject>Anti-HIV Agents - therapeutic use</subject><subject>Antiretroviral agents</subject><subject>Antiretroviral therapy</subject><subject>Darunavir</subject><subject>dolutegravir</subject><subject>drug resistance</subject><subject>dual therapy</subject><subject>genotypic susceptibility score</subject><subject>Heterocyclic Compounds, 3-Ring</subject><subject>HIV</subject><subject>HIV Infections - drug therapy</subject><subject>HIV-1 - genetics</subject><subject>HIV‐1</subject><subject>Human immunodeficiency virus</subject><subject>Humans</subject><subject>Integrase</subject><subject>Mutation</subject><subject>Oxazines</subject><subject>Patients</subject><subject>Piperazines</subject><subject>Protease</subject><subject>Protease inhibitors</subject><subject>Proteinase inhibitors</subject><subject>Pyridones</subject><subject>Retrospective Studies</subject><subject>RNA-directed DNA polymerase</subject><subject>Therapy</subject><subject>Viral Load</subject><subject>virological response</subject><issn>1464-2662</issn><issn>1468-1293</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><recordid>eNp1kc9uFSEUxonR2Fpd-AKGxI0upuXPDMLSNGqbNHGj3RIGztxLw4URmLZ35yP4Jr6TTyL33urCRBLC4eOXjwMfQi8pOaVtnK397SnlRLBH6Jj2QnaUKf54X_cdE4IdoWel3BBC33FFnqIjzntJiOqP0c9rn1NIK29NwBnKnGIBbKLbbXypJlrAc06TD4B9xGu_WoctrhlM3UCsv77_gPsZsocGOnxxed0U2qaPE9japNnUdlgLLne-2rWPK1wTdiksFVbZ3PqM57AUPKZUdrwzeYl7uV1ng4_71uZsbPUWnqMnkwkFXjysJ-jrxw9fzi-6q8-fLs_fX3WWS8k64CMQKtRkhVTUGacGYNTRwVpQVo7GGm6Im5ziIN0oHbfTwPjIuetHwik_QW8Ovu3t3xYoVW98sRCCiZCWoln7QCaGQYmGvv4HvUlLjq07zQYuJOVU7AzfHiibUykZJj1nvzF5qynRuxR1S1HvU2zsqwfHZdyA-0v-ia0BZwfgrsWy_b-TbnkcLH8Diriuuw</recordid><startdate>202107</startdate><enddate>202107</enddate><creator>Armenia, Daniele</creator><creator>Bouba, Yagai</creator><creator>Gagliardini, Roberta</creator><creator>Fabeni, Lavinia</creator><creator>Borghi, Vanni</creator><creator>Berno, Giulia</creator><creator>Vergori, Alessandra</creator><creator>Cicalini, Stefania</creator><creator>Mussini, Cristina</creator><creator>Antinori, Andrea</creator><creator>Ceccherini‐Silberstein, Francesca</creator><creator>Perno, Carlo Federico</creator><creator>Santoro, Maria Mercedes</creator><general>Wiley Subscription Services, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7U7</scope><scope>7U9</scope><scope>C1K</scope><scope>H94</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-6944-0686</orcidid><orcidid>https://orcid.org/0000-0002-6228-1114</orcidid><orcidid>https://orcid.org/0000-0002-3406-7014</orcidid></search><sort><creationdate>202107</creationdate><title>Virological response and resistance profile in highly treatment‐experienced HIV‐1‐infected patients switching to dolutegravir plus boosted darunavir in clinical practice</title><author>Armenia, Daniele ; Bouba, Yagai ; Gagliardini, Roberta ; Fabeni, Lavinia ; Borghi, Vanni ; Berno, Giulia ; Vergori, Alessandra ; Cicalini, Stefania ; Mussini, Cristina ; Antinori, Andrea ; Ceccherini‐Silberstein, Francesca ; Perno, Carlo Federico ; Santoro, Maria Mercedes</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3882-e3be0169fc6891dad95e21d15cce9c8baca3a0dfd93e8db8d3cf523b33d4b0313</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Anti-HIV Agents - pharmacology</topic><topic>Anti-HIV Agents - therapeutic use</topic><topic>Antiretroviral agents</topic><topic>Antiretroviral therapy</topic><topic>Darunavir</topic><topic>dolutegravir</topic><topic>drug resistance</topic><topic>dual therapy</topic><topic>genotypic susceptibility score</topic><topic>Heterocyclic Compounds, 3-Ring</topic><topic>HIV</topic><topic>HIV Infections - drug therapy</topic><topic>HIV-1 - genetics</topic><topic>HIV‐1</topic><topic>Human immunodeficiency virus</topic><topic>Humans</topic><topic>Integrase</topic><topic>Mutation</topic><topic>Oxazines</topic><topic>Patients</topic><topic>Piperazines</topic><topic>Protease</topic><topic>Protease inhibitors</topic><topic>Proteinase inhibitors</topic><topic>Pyridones</topic><topic>Retrospective Studies</topic><topic>RNA-directed DNA polymerase</topic><topic>Therapy</topic><topic>Viral Load</topic><topic>virological response</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Armenia, Daniele</creatorcontrib><creatorcontrib>Bouba, Yagai</creatorcontrib><creatorcontrib>Gagliardini, Roberta</creatorcontrib><creatorcontrib>Fabeni, Lavinia</creatorcontrib><creatorcontrib>Borghi, Vanni</creatorcontrib><creatorcontrib>Berno, Giulia</creatorcontrib><creatorcontrib>Vergori, Alessandra</creatorcontrib><creatorcontrib>Cicalini, Stefania</creatorcontrib><creatorcontrib>Mussini, Cristina</creatorcontrib><creatorcontrib>Antinori, Andrea</creatorcontrib><creatorcontrib>Ceccherini‐Silberstein, Francesca</creatorcontrib><creatorcontrib>Perno, Carlo Federico</creatorcontrib><creatorcontrib>Santoro, Maria Mercedes</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>HIV medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Armenia, Daniele</au><au>Bouba, Yagai</au><au>Gagliardini, Roberta</au><au>Fabeni, Lavinia</au><au>Borghi, Vanni</au><au>Berno, Giulia</au><au>Vergori, Alessandra</au><au>Cicalini, Stefania</au><au>Mussini, Cristina</au><au>Antinori, Andrea</au><au>Ceccherini‐Silberstein, Francesca</au><au>Perno, Carlo Federico</au><au>Santoro, Maria Mercedes</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Virological response and resistance profile in highly treatment‐experienced HIV‐1‐infected patients switching to dolutegravir plus boosted darunavir in clinical practice</atitle><jtitle>HIV medicine</jtitle><addtitle>HIV Med</addtitle><date>2021-07</date><risdate>2021</risdate><volume>22</volume><issue>6</issue><spage>519</spage><epage>525</epage><pages>519-525</pages><issn>1464-2662</issn><eissn>1468-1293</eissn><abstract>Objectives
We evaluated the virological response and resistance profile in combined antiretroviral therapy (cART)‐experienced HIV‐1‐infected patients starting a dual therapy with dolutegravir (DTG) and boosted darunavir (bDRV) for the first time.
Methods
Survival analyses were used to evaluate virological success (VS) and virological rebound (VR) in viraemic and virologically suppressed patients, respectively. Major resistance mutations (MRMs) and genotypic susceptibility score (GSS) were evaluated at baseline and after switch.
Results
Overall, 130 patients [62 (47.7%) viraemic; 68 (52.3%) virologically suppressed] were retrospectively analysed. At the moment of switch, 81.5% accumulated one or more MRM [protease inhibitor (PI), 35.7%; nucleoside(t)ide reverse transcriptase inhibitor (NRTI), 77.5%; non‐NRTI, 69.0%; integrase inhibitor (INI), 10.1%), but 77.7% harboured strains fully susceptible to DTG + bDRV. In viraemic patients, the overall probability of VS by 12 months of treatment was 91.7%. In virologically suppressed patients, the overall probability of VR was 10.5% by 24 months after therapy start. Patients with previous time under virological suppression ≤ 6 months showed a higher VR probability compared with others (37.5% vs. 6.7%, P < 0.002). Among 13 non‐responding patients for whom a genotypic resistance test result at failure was available, only two (15.4%) accumulated further resistance in integrase (Y143C/H/R; S147G and N155H) and protease (V32I, L33F, I54L).
Conclusions
In highly treatment‐experienced patients, the use of dual therapy based on DTG + bDRV appears to be a very good regimen for switch therapy, with a high rate of virological control in both viraemic and virologically suppressed patients. Among non‐responding patients, the selection of further resistance is a rare event.</abstract><cop>England</cop><pub>Wiley Subscription Services, Inc</pub><pmid>33480094</pmid><doi>10.1111/hiv.13062</doi><tpages>7</tpages><orcidid>https://orcid.org/0000-0001-6944-0686</orcidid><orcidid>https://orcid.org/0000-0002-6228-1114</orcidid><orcidid>https://orcid.org/0000-0002-3406-7014</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | HIV medicine, 2021-07, Vol.22 (6), p.519-525 |
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| language | eng |
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| source | Wiley-Blackwell Read & Publish Collection |
| subjects | Anti-HIV Agents - pharmacology Anti-HIV Agents - therapeutic use Antiretroviral agents Antiretroviral therapy Darunavir dolutegravir drug resistance dual therapy genotypic susceptibility score Heterocyclic Compounds, 3-Ring HIV HIV Infections - drug therapy HIV-1 - genetics HIV‐1 Human immunodeficiency virus Humans Integrase Mutation Oxazines Patients Piperazines Protease Protease inhibitors Proteinase inhibitors Pyridones Retrospective Studies RNA-directed DNA polymerase Therapy Viral Load virological response |
| title | Virological response and resistance profile in highly treatment‐experienced HIV‐1‐infected patients switching to dolutegravir plus boosted darunavir in clinical practice |
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