Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate (TDF) Versus Efavirenz/Emtricitabine/TDF in Treatment-naive Adults With Human Immunodeficiency Virus Type 1 Infection: Week 96 Results of the Randomized, Double-blind, Phase 3 DRIVE-AHEAD Noninferiority Trial
Doravirine (DOR) is a nonnucleoside reverse-transcriptase inhibitor. In the phase 3 DRIVE-AHEAD trial in treatment-naive adults with human immunodeficiency virus type 1 (HIV-1) infection, DOR demonstrated noninferior efficacy compared with efavirenz (EFV) and superior profiles for neuropsychiatric t...
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| Veröffentlicht in: | Clinical infectious diseases 2021-07, Vol.73 (1), p.33-42 |
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| creator | Orkin, Chloe Squires, Kathleen E Molina, Jean-Michel Sax, Paul E Sussmann, Otto Lin, Gina Kumar, Sushma Hanna, George J Hwang, Carey Martin, Elizabeth Teppler, Hedy |
| description | Doravirine (DOR) is a nonnucleoside reverse-transcriptase inhibitor. In the phase 3 DRIVE-AHEAD trial in treatment-naive adults with human immunodeficiency virus type 1 (HIV-1) infection, DOR demonstrated noninferior efficacy compared with efavirenz (EFV) and superior profiles for neuropsychiatric tolerability and lipids at 48 weeks. We present data through week 96.
DRIVE-AHEAD is a phase 3, multicenter, double-blind, noninferiority trial in antiretroviral treatment-naive adults with HIV-1 RNA ≥1000 copies/mL. Participants were randomized to a daily fixed-dose tablet of DOR (100 mg), lamivudine (3TC; 300 mg) and tenofovir disoproxil fumarate (TDF; 300 mg) (DOR/3TC/TDF) or EFV (600 mg), emtricitabine (FTC; 200 mg) and TDF (300 mg) (EFV/FTC/TDF). The efficacy end point of interest at week 96 was the proportion of participants with HIV-1 RNA levels |
| doi_str_mv | 10.1093/cid/ciaa822 |
| format | Article |
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DRIVE-AHEAD is a phase 3, multicenter, double-blind, noninferiority trial in antiretroviral treatment-naive adults with HIV-1 RNA ≥1000 copies/mL. Participants were randomized to a daily fixed-dose tablet of DOR (100 mg), lamivudine (3TC; 300 mg) and tenofovir disoproxil fumarate (TDF; 300 mg) (DOR/3TC/TDF) or EFV (600 mg), emtricitabine (FTC; 200 mg) and TDF (300 mg) (EFV/FTC/TDF). The efficacy end point of interest at week 96 was the proportion of participants with HIV-1 RNA levels <50 copies/mL (Food and Drug Administration Snapshot Approach) with a predefined noninferiority margin of 10% to support week 48 results. Safety end points of interest included prespecified neuropsychiatric adverse events and the mean change in fasting lipids at week 96.
Of 734 participants randomized, 728 received study drugs and were included in analyses. At week 96, HIV-1 RNA <50 copies/mL was achieved by 77.5% of DOR/3TC/TDF vs 73.6% of EFV/FTC/TDF participants, with a treatment difference of 3.8% (95% confidence interval, -2.4% to 10%). Virologic failure rates were low and similar across treatment arms, with no additional resistance to DOR observed between weeks 48 and 96. Prespecified neuropsychiatric adverse events and rash were less frequent in DOR/3TC/TDF than in EFV/FTC/TDF participants through week 96. At week 96, fasting low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol (HDL-C) levels increased in the EFV/FTC/TDF group but not in the DOR/3TC/TDF group; the mean changes from baseline in total cholesterol/HDL-C ratio were similar.
NCT02403674.</description><identifier>ISSN: 1058-4838</identifier><identifier>EISSN: 1537-6591</identifier><identifier>DOI: 10.1093/cid/ciaa822</identifier><identifier>PMID: 33336698</identifier><language>eng</language><publisher>United States: Oxford University Press</publisher><subject>Adult ; Alkynes ; Anti-HIV Agents - adverse effects ; Benzoxazines ; Cyclopropanes ; Emtricitabine - therapeutic use ; Fumarates - therapeutic use ; HIV Infections - drug therapy ; HIV-1 ; Humans ; Lamivudine - adverse effects ; Major and Commentaries ; Pyridones ; Tenofovir - therapeutic use ; Treatment Outcome ; Triazoles</subject><ispartof>Clinical infectious diseases, 2021-07, Vol.73 (1), p.33-42</ispartof><rights>The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.</rights><rights>The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c381t-87703c6c0b47ba6d3fa1401958dad55f2088ca59a33291dcdd555d642e3f32a93</citedby><cites>FETCH-LOGICAL-c381t-87703c6c0b47ba6d3fa1401958dad55f2088ca59a33291dcdd555d642e3f32a93</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33336698$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Orkin, Chloe</creatorcontrib><creatorcontrib>Squires, Kathleen E</creatorcontrib><creatorcontrib>Molina, Jean-Michel</creatorcontrib><creatorcontrib>Sax, Paul E</creatorcontrib><creatorcontrib>Sussmann, Otto</creatorcontrib><creatorcontrib>Lin, Gina</creatorcontrib><creatorcontrib>Kumar, Sushma</creatorcontrib><creatorcontrib>Hanna, George J</creatorcontrib><creatorcontrib>Hwang, Carey</creatorcontrib><creatorcontrib>Martin, Elizabeth</creatorcontrib><creatorcontrib>Teppler, Hedy</creatorcontrib><title>Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate (TDF) Versus Efavirenz/Emtricitabine/TDF in Treatment-naive Adults With Human Immunodeficiency Virus Type 1 Infection: Week 96 Results of the Randomized, Double-blind, Phase 3 DRIVE-AHEAD Noninferiority Trial</title><title>Clinical infectious diseases</title><addtitle>Clin Infect Dis</addtitle><description>Doravirine (DOR) is a nonnucleoside reverse-transcriptase inhibitor. In the phase 3 DRIVE-AHEAD trial in treatment-naive adults with human immunodeficiency virus type 1 (HIV-1) infection, DOR demonstrated noninferior efficacy compared with efavirenz (EFV) and superior profiles for neuropsychiatric tolerability and lipids at 48 weeks. We present data through week 96.
DRIVE-AHEAD is a phase 3, multicenter, double-blind, noninferiority trial in antiretroviral treatment-naive adults with HIV-1 RNA ≥1000 copies/mL. Participants were randomized to a daily fixed-dose tablet of DOR (100 mg), lamivudine (3TC; 300 mg) and tenofovir disoproxil fumarate (TDF; 300 mg) (DOR/3TC/TDF) or EFV (600 mg), emtricitabine (FTC; 200 mg) and TDF (300 mg) (EFV/FTC/TDF). The efficacy end point of interest at week 96 was the proportion of participants with HIV-1 RNA levels <50 copies/mL (Food and Drug Administration Snapshot Approach) with a predefined noninferiority margin of 10% to support week 48 results. Safety end points of interest included prespecified neuropsychiatric adverse events and the mean change in fasting lipids at week 96.
Of 734 participants randomized, 728 received study drugs and were included in analyses. At week 96, HIV-1 RNA <50 copies/mL was achieved by 77.5% of DOR/3TC/TDF vs 73.6% of EFV/FTC/TDF participants, with a treatment difference of 3.8% (95% confidence interval, -2.4% to 10%). Virologic failure rates were low and similar across treatment arms, with no additional resistance to DOR observed between weeks 48 and 96. Prespecified neuropsychiatric adverse events and rash were less frequent in DOR/3TC/TDF than in EFV/FTC/TDF participants through week 96. At week 96, fasting low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol (HDL-C) levels increased in the EFV/FTC/TDF group but not in the DOR/3TC/TDF group; the mean changes from baseline in total cholesterol/HDL-C ratio were similar.
NCT02403674.</description><subject>Adult</subject><subject>Alkynes</subject><subject>Anti-HIV Agents - adverse effects</subject><subject>Benzoxazines</subject><subject>Cyclopropanes</subject><subject>Emtricitabine - therapeutic use</subject><subject>Fumarates - therapeutic use</subject><subject>HIV Infections - drug therapy</subject><subject>HIV-1</subject><subject>Humans</subject><subject>Lamivudine - adverse effects</subject><subject>Major and Commentaries</subject><subject>Pyridones</subject><subject>Tenofovir - therapeutic use</subject><subject>Treatment Outcome</subject><subject>Triazoles</subject><issn>1058-4838</issn><issn>1537-6591</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkt9v0zAQxwMaYmPwxDvy4xCExnF-OHtAqpaWVqoAVaV7jFz7Qg8Su9hORffX425lAkuWz-fvfXw6faPoNU0-0KRiI4kqbCF4mj6NLmjOyrjIK3oW4iTnccYZP49eOPcjSSjlSf48OmdhFUXFL56c1caKPVrUMFqIHveDOoYr0KY1IU9qdGZnzW_syHTohRUeyNWqnr4la7BucGTSHutB340mvbco0YvNPaKeEtRkZUH4HrSPtcA9kLEaOu_ILfotmQWgJvO-H7RR0IZa0PJA1mgDd3XYAaFkrluQHo2-JrcAP0lVkCW4e4Zpid8CWQqtTI93oN6T2gybDuJNhzrcvm6FA8JIvZyvJ_F4NhnX5LPRGJAWjUV_CO2h6F5Gz1rROXh1Oi-jb9PJ6mYWL758mt-MF7FknPqYl2XCZCGTTVZuRKFYK2iW0CrnSqg8b9OEcynySjCWVlRJFZK5KrIUWMtSUbHL6OMDdzdselAyTMWKrtlZDIM9NEZg8_-Lxm3z3ewbnmYFr1gAXJ0A1vwawPmmRyeh64QGM7gmzUqaFWWWlUH67kEqrXHOQvv4DU2ao2-a4Jvm5JugfvNvZ4_av0ZhfwD4WcOO</recordid><startdate>20210701</startdate><enddate>20210701</enddate><creator>Orkin, Chloe</creator><creator>Squires, Kathleen E</creator><creator>Molina, Jean-Michel</creator><creator>Sax, Paul E</creator><creator>Sussmann, Otto</creator><creator>Lin, Gina</creator><creator>Kumar, Sushma</creator><creator>Hanna, George J</creator><creator>Hwang, Carey</creator><creator>Martin, Elizabeth</creator><creator>Teppler, Hedy</creator><general>Oxford University Press</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>7X8</scope><scope>5PM</scope></search><sort><creationdate>20210701</creationdate><title>Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate (TDF) Versus Efavirenz/Emtricitabine/TDF in Treatment-naive Adults With Human Immunodeficiency Virus Type 1 Infection: Week 96 Results of the Randomized, Double-blind, Phase 3 DRIVE-AHEAD Noninferiority Trial</title><author>Orkin, Chloe ; Squires, Kathleen E ; Molina, Jean-Michel ; Sax, Paul E ; Sussmann, Otto ; Lin, Gina ; Kumar, Sushma ; Hanna, George J ; Hwang, Carey ; Martin, Elizabeth ; Teppler, Hedy</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c381t-87703c6c0b47ba6d3fa1401958dad55f2088ca59a33291dcdd555d642e3f32a93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Adult</topic><topic>Alkynes</topic><topic>Anti-HIV Agents - adverse effects</topic><topic>Benzoxazines</topic><topic>Cyclopropanes</topic><topic>Emtricitabine - therapeutic use</topic><topic>Fumarates - therapeutic use</topic><topic>HIV Infections - drug therapy</topic><topic>HIV-1</topic><topic>Humans</topic><topic>Lamivudine - adverse effects</topic><topic>Major and Commentaries</topic><topic>Pyridones</topic><topic>Tenofovir - therapeutic use</topic><topic>Treatment Outcome</topic><topic>Triazoles</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Orkin, Chloe</creatorcontrib><creatorcontrib>Squires, Kathleen E</creatorcontrib><creatorcontrib>Molina, Jean-Michel</creatorcontrib><creatorcontrib>Sax, Paul E</creatorcontrib><creatorcontrib>Sussmann, Otto</creatorcontrib><creatorcontrib>Lin, Gina</creatorcontrib><creatorcontrib>Kumar, Sushma</creatorcontrib><creatorcontrib>Hanna, George J</creatorcontrib><creatorcontrib>Hwang, Carey</creatorcontrib><creatorcontrib>Martin, Elizabeth</creatorcontrib><creatorcontrib>Teppler, Hedy</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Clinical infectious diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Orkin, Chloe</au><au>Squires, Kathleen E</au><au>Molina, Jean-Michel</au><au>Sax, Paul E</au><au>Sussmann, Otto</au><au>Lin, Gina</au><au>Kumar, Sushma</au><au>Hanna, George J</au><au>Hwang, Carey</au><au>Martin, Elizabeth</au><au>Teppler, Hedy</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate (TDF) Versus Efavirenz/Emtricitabine/TDF in Treatment-naive Adults With Human Immunodeficiency Virus Type 1 Infection: Week 96 Results of the Randomized, Double-blind, Phase 3 DRIVE-AHEAD Noninferiority Trial</atitle><jtitle>Clinical infectious diseases</jtitle><addtitle>Clin Infect Dis</addtitle><date>2021-07-01</date><risdate>2021</risdate><volume>73</volume><issue>1</issue><spage>33</spage><epage>42</epage><pages>33-42</pages><issn>1058-4838</issn><eissn>1537-6591</eissn><abstract>Doravirine (DOR) is a nonnucleoside reverse-transcriptase inhibitor. In the phase 3 DRIVE-AHEAD trial in treatment-naive adults with human immunodeficiency virus type 1 (HIV-1) infection, DOR demonstrated noninferior efficacy compared with efavirenz (EFV) and superior profiles for neuropsychiatric tolerability and lipids at 48 weeks. We present data through week 96.
DRIVE-AHEAD is a phase 3, multicenter, double-blind, noninferiority trial in antiretroviral treatment-naive adults with HIV-1 RNA ≥1000 copies/mL. Participants were randomized to a daily fixed-dose tablet of DOR (100 mg), lamivudine (3TC; 300 mg) and tenofovir disoproxil fumarate (TDF; 300 mg) (DOR/3TC/TDF) or EFV (600 mg), emtricitabine (FTC; 200 mg) and TDF (300 mg) (EFV/FTC/TDF). The efficacy end point of interest at week 96 was the proportion of participants with HIV-1 RNA levels <50 copies/mL (Food and Drug Administration Snapshot Approach) with a predefined noninferiority margin of 10% to support week 48 results. Safety end points of interest included prespecified neuropsychiatric adverse events and the mean change in fasting lipids at week 96.
Of 734 participants randomized, 728 received study drugs and were included in analyses. At week 96, HIV-1 RNA <50 copies/mL was achieved by 77.5% of DOR/3TC/TDF vs 73.6% of EFV/FTC/TDF participants, with a treatment difference of 3.8% (95% confidence interval, -2.4% to 10%). Virologic failure rates were low and similar across treatment arms, with no additional resistance to DOR observed between weeks 48 and 96. Prespecified neuropsychiatric adverse events and rash were less frequent in DOR/3TC/TDF than in EFV/FTC/TDF participants through week 96. At week 96, fasting low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol (HDL-C) levels increased in the EFV/FTC/TDF group but not in the DOR/3TC/TDF group; the mean changes from baseline in total cholesterol/HDL-C ratio were similar.
NCT02403674.</abstract><cop>United States</cop><pub>Oxford University Press</pub><pmid>33336698</pmid><doi>10.1093/cid/ciaa822</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1058-4838 |
| ispartof | Clinical infectious diseases, 2021-07, Vol.73 (1), p.33-42 |
| issn | 1058-4838 1537-6591 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8246893 |
| source | Oxford University Press Journals All Titles (1996-Current); MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Adult Alkynes Anti-HIV Agents - adverse effects Benzoxazines Cyclopropanes Emtricitabine - therapeutic use Fumarates - therapeutic use HIV Infections - drug therapy HIV-1 Humans Lamivudine - adverse effects Major and Commentaries Pyridones Tenofovir - therapeutic use Treatment Outcome Triazoles |
| title | Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate (TDF) Versus Efavirenz/Emtricitabine/TDF in Treatment-naive Adults With Human Immunodeficiency Virus Type 1 Infection: Week 96 Results of the Randomized, Double-blind, Phase 3 DRIVE-AHEAD Noninferiority Trial |
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