Effectiveness of Transmitted Drug Resistance Testing Before Initiation of Antiretroviral Therapy in HIV-Positive Individuals
BACKGROUND:For people living with HIV, major guidelines in high-income countries recommend testing for transmitted drug resistance (TDR) to guide the choice of first-line antiretroviral therapy (ART). However, individuals who fail a first-line regimen can now be switched to one of several effective...
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| Veröffentlicht in: | Journal of acquired immune deficiency syndromes (1999) 2019-11, Vol.82 (3), p.314-320 |
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| creator | Lodi, Sara Günthard, Huldrych F Gill, John Phillips, Andrew N Dunn, David Vu, Quang Siemieniuk, Reed Garcia, Federico Logan, Roger Jose, Sophie Bucher, Heiner C Scherrer, Alexandra U Reiss, Peter van Sighem, Ard Boender, T Sonia Porter, Kholoud Gilson, Richard Paraskevis, Dimitrios Simeon, Metallidis Vourli, Georgia Moreno, Santiago Jarrin, Inmaculada Sabin, Caroline Hernán, Miguel A |
| description | BACKGROUND:For people living with HIV, major guidelines in high-income countries recommend testing for transmitted drug resistance (TDR) to guide the choice of first-line antiretroviral therapy (ART). However, individuals who fail a first-line regimen can now be switched to one of several effective regimens. Therefore, the virological and clinical benefit of TDR testing needs to be evaluated.
METHODS:We included individuals from the HIV-CAUSAL Collaboration who enrolled |
| doi_str_mv | 10.1097/QAI.0000000000002135 |
| format | Article |
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METHODS:We included individuals from the HIV-CAUSAL Collaboration who enrolled <6 months of HIV diagnosis between 2006 and 2015, were ART-naive, and had measured CD4 count and HIV-RNA. Follow-up started at the date when all inclusion criteria were first met (baseline). We compared 2 strategies(1) TDR testing within 3 months of baseline versus (2) no TDR testing. We used inverse probability weighting to estimate the 5-year proportion and hazard ratios (HRs) of virological suppression (confirmed HIV-RNA <50 copies/mL), and of AIDS or death under both strategies.
RESULTS:Of 25,672 eligible individuals (82% males, 52% diagnosed in 2010 or later), 17,189 (67%) were tested for TDR within 3 months of baseline. Of these, 6% had intermediate- or high-level TDR to any antiretroviral drug. The estimated 5-year proportion virologically suppressed was 77% under TDR testing and 74% under no TDR testing; HR 1.06 (95% confidence interval1.03 to 1.19). The estimated 5-year risk of AIDS or death was 6% under both strategies; HR 1.03 (95% confidence interval0.95 to 1.12).
CONCLUSIONS:TDR prevalence was low. Although TDR testing improved virological response, we found no evidence that it reduced the incidence of AIDS or death in first 5 years after diagnosis.</description><identifier>ISSN: 1525-4135</identifier><identifier>ISSN: 1944-7884</identifier><identifier>EISSN: 1944-7884</identifier><identifier>DOI: 10.1097/QAI.0000000000002135</identifier><identifier>PMID: 31609929</identifier><language>eng</language><publisher>United States: Copyright Wolters Kluwer Health, Inc. All rights reserved</publisher><subject>Acquired immune deficiency syndrome ; Adult ; AIDS ; Anti-HIV Agents - therapeutic use ; Anti-Retroviral Agents - therapeutic use ; Antiretroviral agents ; Antiretroviral drugs ; Antiretroviral therapy ; CD4 antigen ; CD4 Lymphocyte Count ; Confidence intervals ; Death ; Diagnosis ; Drug resistance ; Drug Resistance, Viral - drug effects ; Drug therapy ; Drug Therapy, Combination ; Female ; HIV ; HIV Infections - drug therapy ; HIV Infections - transmission ; HIV Infections - virology ; HIV-1 - drug effects ; Human immunodeficiency virus ; Humans ; Male ; Males ; Middle Aged ; Mortality ; Ribonucleic acid ; RNA ; Statistical analysis ; Therapy</subject><ispartof>Journal of acquired immune deficiency syndromes (1999), 2019-11, Vol.82 (3), p.314-320</ispartof><rights>Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.</rights><rights>Copyright Lippincott Williams & Wilkins Ovid Technologies Nov 1, 2019</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4812-ce31826621f3e85c559ce248bdc962035cc25b5d382ce97e04951087aa0f0e4d3</citedby><cites>FETCH-LOGICAL-c4812-ce31826621f3e85c559ce248bdc962035cc25b5d382ce97e04951087aa0f0e4d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf><![CDATA[$$Uhttp://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&PDF=y&D=ovft&AN=00126334-201911010-00012$$EPDF$$P50$$Gwolterskluwer$$H]]></linktopdf><linktohtml>$$Uhttp://ovidsp.ovid.com/ovidweb.cgi?T=JS&NEWS=n&CSC=Y&PAGE=fulltext&D=ovft&AN=00126334-201911010-00012$$EHTML$$P50$$Gwolterskluwer$$H</linktohtml><link.rule.ids>230,314,780,784,885,4609,27924,27925,64666,65461</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31609929$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lodi, Sara</creatorcontrib><creatorcontrib>Günthard, Huldrych F</creatorcontrib><creatorcontrib>Gill, John</creatorcontrib><creatorcontrib>Phillips, Andrew N</creatorcontrib><creatorcontrib>Dunn, David</creatorcontrib><creatorcontrib>Vu, Quang</creatorcontrib><creatorcontrib>Siemieniuk, Reed</creatorcontrib><creatorcontrib>Garcia, Federico</creatorcontrib><creatorcontrib>Logan, Roger</creatorcontrib><creatorcontrib>Jose, Sophie</creatorcontrib><creatorcontrib>Bucher, Heiner C</creatorcontrib><creatorcontrib>Scherrer, Alexandra U</creatorcontrib><creatorcontrib>Reiss, Peter</creatorcontrib><creatorcontrib>van Sighem, Ard</creatorcontrib><creatorcontrib>Boender, T Sonia</creatorcontrib><creatorcontrib>Porter, Kholoud</creatorcontrib><creatorcontrib>Gilson, Richard</creatorcontrib><creatorcontrib>Paraskevis, Dimitrios</creatorcontrib><creatorcontrib>Simeon, Metallidis</creatorcontrib><creatorcontrib>Vourli, Georgia</creatorcontrib><creatorcontrib>Moreno, Santiago</creatorcontrib><creatorcontrib>Jarrin, Inmaculada</creatorcontrib><creatorcontrib>Sabin, Caroline</creatorcontrib><creatorcontrib>Hernán, Miguel A</creatorcontrib><creatorcontrib>on behalf of the HIV-CAUSAL Collaboration</creatorcontrib><title>Effectiveness of Transmitted Drug Resistance Testing Before Initiation of Antiretroviral Therapy in HIV-Positive Individuals</title><title>Journal of acquired immune deficiency syndromes (1999)</title><addtitle>J Acquir Immune Defic Syndr</addtitle><description>BACKGROUND:For people living with HIV, major guidelines in high-income countries recommend testing for transmitted drug resistance (TDR) to guide the choice of first-line antiretroviral therapy (ART). However, individuals who fail a first-line regimen can now be switched to one of several effective regimens. Therefore, the virological and clinical benefit of TDR testing needs to be evaluated.
METHODS:We included individuals from the HIV-CAUSAL Collaboration who enrolled <6 months of HIV diagnosis between 2006 and 2015, were ART-naive, and had measured CD4 count and HIV-RNA. Follow-up started at the date when all inclusion criteria were first met (baseline). We compared 2 strategies(1) TDR testing within 3 months of baseline versus (2) no TDR testing. We used inverse probability weighting to estimate the 5-year proportion and hazard ratios (HRs) of virological suppression (confirmed HIV-RNA <50 copies/mL), and of AIDS or death under both strategies.
RESULTS:Of 25,672 eligible individuals (82% males, 52% diagnosed in 2010 or later), 17,189 (67%) were tested for TDR within 3 months of baseline. Of these, 6% had intermediate- or high-level TDR to any antiretroviral drug. The estimated 5-year proportion virologically suppressed was 77% under TDR testing and 74% under no TDR testing; HR 1.06 (95% confidence interval1.03 to 1.19). The estimated 5-year risk of AIDS or death was 6% under both strategies; HR 1.03 (95% confidence interval0.95 to 1.12).
CONCLUSIONS:TDR prevalence was low. Although TDR testing improved virological response, we found no evidence that it reduced the incidence of AIDS or death in first 5 years after diagnosis.</description><subject>Acquired immune deficiency syndrome</subject><subject>Adult</subject><subject>AIDS</subject><subject>Anti-HIV Agents - therapeutic use</subject><subject>Anti-Retroviral Agents - therapeutic use</subject><subject>Antiretroviral agents</subject><subject>Antiretroviral drugs</subject><subject>Antiretroviral therapy</subject><subject>CD4 antigen</subject><subject>CD4 Lymphocyte Count</subject><subject>Confidence intervals</subject><subject>Death</subject><subject>Diagnosis</subject><subject>Drug resistance</subject><subject>Drug Resistance, Viral - drug effects</subject><subject>Drug therapy</subject><subject>Drug Therapy, Combination</subject><subject>Female</subject><subject>HIV</subject><subject>HIV Infections - drug therapy</subject><subject>HIV Infections - transmission</subject><subject>HIV Infections - virology</subject><subject>HIV-1 - drug effects</subject><subject>Human immunodeficiency virus</subject><subject>Humans</subject><subject>Male</subject><subject>Males</subject><subject>Middle Aged</subject><subject>Mortality</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>Statistical analysis</subject><subject>Therapy</subject><issn>1525-4135</issn><issn>1944-7884</issn><issn>1944-7884</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdUU1vEzEUtBCIlsA_QMgSFy5b_LleX5BCKTRSJT4UuFqO923isrGD7U1ViR-Po5ZS6suznmfmzfMg9JKSE0q0evt1vjgh9w6jXD5Cx1QL0aiuE4_rXTLZiNo_Qs9yviSEtkLop-iI05ZozfQx-n02DOCK30OAnHEc8DLZkLe-FOjxhzSt8TfIPhcbHOAl5OLDGr-HISbAi-CLt8XHcCDOQ_EJSop7n-yIlxtIdneNfcDnix_Nl5j9YUwl9X7v-8mO-Tl6MtQCL27rDH3_eLY8PW8uPn9anM4vGic6yhoHnHasbRkdOHTSSakdMNGteqdbRrh0jsmV7HnHHGgFRGhJSaesJQMB0fMZeneju5tWW-gdhFIdml3yW5uuTbTe_P8S_Mas496ojhOlVBV4cyuQ4q-pfoLZ-uxgHG2AOGXDOJFKK1nNzNDrB9DLOKVQ1zug2ooiVFeUuEG5FHNOMNyZocQc4jU1XvMw3kp7dX-RO9LfPP_pXsWxQMo_x-kKktmAHcum6lHWci4aVj1QSihpyKHH_wDXM7GW</recordid><startdate>20191101</startdate><enddate>20191101</enddate><creator>Lodi, Sara</creator><creator>Günthard, Huldrych F</creator><creator>Gill, John</creator><creator>Phillips, Andrew N</creator><creator>Dunn, David</creator><creator>Vu, Quang</creator><creator>Siemieniuk, Reed</creator><creator>Garcia, Federico</creator><creator>Logan, Roger</creator><creator>Jose, Sophie</creator><creator>Bucher, Heiner C</creator><creator>Scherrer, Alexandra U</creator><creator>Reiss, Peter</creator><creator>van Sighem, Ard</creator><creator>Boender, T Sonia</creator><creator>Porter, Kholoud</creator><creator>Gilson, Richard</creator><creator>Paraskevis, Dimitrios</creator><creator>Simeon, Metallidis</creator><creator>Vourli, Georgia</creator><creator>Moreno, Santiago</creator><creator>Jarrin, Inmaculada</creator><creator>Sabin, Caroline</creator><creator>Hernán, Miguel A</creator><general>Copyright Wolters Kluwer Health, Inc. All rights reserved</general><general>Lippincott Williams & Wilkins Ovid Technologies</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>7T2</scope><scope>7T5</scope><scope>7TK</scope><scope>7U7</scope><scope>7U9</scope><scope>C1K</scope><scope>H94</scope><scope>K9.</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20191101</creationdate><title>Effectiveness of Transmitted Drug Resistance Testing Before Initiation of Antiretroviral Therapy in HIV-Positive Individuals</title><author>Lodi, Sara ; Günthard, Huldrych F ; Gill, John ; Phillips, Andrew N ; Dunn, David ; Vu, Quang ; Siemieniuk, Reed ; Garcia, Federico ; Logan, Roger ; Jose, Sophie ; Bucher, Heiner C ; Scherrer, Alexandra U ; Reiss, Peter ; van Sighem, Ard ; Boender, T Sonia ; Porter, Kholoud ; Gilson, Richard ; Paraskevis, Dimitrios ; Simeon, Metallidis ; Vourli, Georgia ; Moreno, Santiago ; Jarrin, Inmaculada ; Sabin, Caroline ; Hernán, Miguel A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4812-ce31826621f3e85c559ce248bdc962035cc25b5d382ce97e04951087aa0f0e4d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Acquired immune deficiency syndrome</topic><topic>Adult</topic><topic>AIDS</topic><topic>Anti-HIV Agents - therapeutic use</topic><topic>Anti-Retroviral Agents - therapeutic use</topic><topic>Antiretroviral agents</topic><topic>Antiretroviral drugs</topic><topic>Antiretroviral therapy</topic><topic>CD4 antigen</topic><topic>CD4 Lymphocyte Count</topic><topic>Confidence intervals</topic><topic>Death</topic><topic>Diagnosis</topic><topic>Drug resistance</topic><topic>Drug Resistance, Viral - drug effects</topic><topic>Drug therapy</topic><topic>Drug Therapy, Combination</topic><topic>Female</topic><topic>HIV</topic><topic>HIV Infections - drug therapy</topic><topic>HIV Infections - transmission</topic><topic>HIV Infections - virology</topic><topic>HIV-1 - drug effects</topic><topic>Human immunodeficiency virus</topic><topic>Humans</topic><topic>Male</topic><topic>Males</topic><topic>Middle Aged</topic><topic>Mortality</topic><topic>Ribonucleic acid</topic><topic>RNA</topic><topic>Statistical analysis</topic><topic>Therapy</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lodi, Sara</creatorcontrib><creatorcontrib>Günthard, Huldrych F</creatorcontrib><creatorcontrib>Gill, John</creatorcontrib><creatorcontrib>Phillips, Andrew N</creatorcontrib><creatorcontrib>Dunn, David</creatorcontrib><creatorcontrib>Vu, Quang</creatorcontrib><creatorcontrib>Siemieniuk, Reed</creatorcontrib><creatorcontrib>Garcia, Federico</creatorcontrib><creatorcontrib>Logan, Roger</creatorcontrib><creatorcontrib>Jose, Sophie</creatorcontrib><creatorcontrib>Bucher, Heiner C</creatorcontrib><creatorcontrib>Scherrer, Alexandra U</creatorcontrib><creatorcontrib>Reiss, Peter</creatorcontrib><creatorcontrib>van Sighem, Ard</creatorcontrib><creatorcontrib>Boender, T Sonia</creatorcontrib><creatorcontrib>Porter, Kholoud</creatorcontrib><creatorcontrib>Gilson, Richard</creatorcontrib><creatorcontrib>Paraskevis, Dimitrios</creatorcontrib><creatorcontrib>Simeon, Metallidis</creatorcontrib><creatorcontrib>Vourli, Georgia</creatorcontrib><creatorcontrib>Moreno, Santiago</creatorcontrib><creatorcontrib>Jarrin, Inmaculada</creatorcontrib><creatorcontrib>Sabin, Caroline</creatorcontrib><creatorcontrib>Hernán, Miguel A</creatorcontrib><creatorcontrib>on behalf of the HIV-CAUSAL Collaboration</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Health and Safety Science Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</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>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of acquired immune deficiency syndromes (1999)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lodi, Sara</au><au>Günthard, Huldrych F</au><au>Gill, John</au><au>Phillips, Andrew N</au><au>Dunn, David</au><au>Vu, Quang</au><au>Siemieniuk, Reed</au><au>Garcia, Federico</au><au>Logan, Roger</au><au>Jose, Sophie</au><au>Bucher, Heiner C</au><au>Scherrer, Alexandra U</au><au>Reiss, Peter</au><au>van Sighem, Ard</au><au>Boender, T Sonia</au><au>Porter, Kholoud</au><au>Gilson, Richard</au><au>Paraskevis, Dimitrios</au><au>Simeon, Metallidis</au><au>Vourli, Georgia</au><au>Moreno, Santiago</au><au>Jarrin, Inmaculada</au><au>Sabin, Caroline</au><au>Hernán, Miguel A</au><aucorp>on behalf of the HIV-CAUSAL Collaboration</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effectiveness of Transmitted Drug Resistance Testing Before Initiation of Antiretroviral Therapy in HIV-Positive Individuals</atitle><jtitle>Journal of acquired immune deficiency syndromes (1999)</jtitle><addtitle>J Acquir Immune Defic Syndr</addtitle><date>2019-11-01</date><risdate>2019</risdate><volume>82</volume><issue>3</issue><spage>314</spage><epage>320</epage><pages>314-320</pages><issn>1525-4135</issn><issn>1944-7884</issn><eissn>1944-7884</eissn><abstract>BACKGROUND:For people living with HIV, major guidelines in high-income countries recommend testing for transmitted drug resistance (TDR) to guide the choice of first-line antiretroviral therapy (ART). However, individuals who fail a first-line regimen can now be switched to one of several effective regimens. Therefore, the virological and clinical benefit of TDR testing needs to be evaluated.
METHODS:We included individuals from the HIV-CAUSAL Collaboration who enrolled <6 months of HIV diagnosis between 2006 and 2015, were ART-naive, and had measured CD4 count and HIV-RNA. Follow-up started at the date when all inclusion criteria were first met (baseline). We compared 2 strategies(1) TDR testing within 3 months of baseline versus (2) no TDR testing. We used inverse probability weighting to estimate the 5-year proportion and hazard ratios (HRs) of virological suppression (confirmed HIV-RNA <50 copies/mL), and of AIDS or death under both strategies.
RESULTS:Of 25,672 eligible individuals (82% males, 52% diagnosed in 2010 or later), 17,189 (67%) were tested for TDR within 3 months of baseline. Of these, 6% had intermediate- or high-level TDR to any antiretroviral drug. The estimated 5-year proportion virologically suppressed was 77% under TDR testing and 74% under no TDR testing; HR 1.06 (95% confidence interval1.03 to 1.19). The estimated 5-year risk of AIDS or death was 6% under both strategies; HR 1.03 (95% confidence interval0.95 to 1.12).
CONCLUSIONS:TDR prevalence was low. Although TDR testing improved virological response, we found no evidence that it reduced the incidence of AIDS or death in first 5 years after diagnosis.</abstract><cop>United States</cop><pub>Copyright Wolters Kluwer Health, Inc. All rights reserved</pub><pmid>31609929</pmid><doi>10.1097/QAI.0000000000002135</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 1525-4135 |
| ispartof | Journal of acquired immune deficiency syndromes (1999), 2019-11, Vol.82 (3), p.314-320 |
| issn | 1525-4135 1944-7884 1944-7884 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7830777 |
| source | MEDLINE; Journals@Ovid LWW Legacy Archive; Free E- Journals |
| subjects | Acquired immune deficiency syndrome Adult AIDS Anti-HIV Agents - therapeutic use Anti-Retroviral Agents - therapeutic use Antiretroviral agents Antiretroviral drugs Antiretroviral therapy CD4 antigen CD4 Lymphocyte Count Confidence intervals Death Diagnosis Drug resistance Drug Resistance, Viral - drug effects Drug therapy Drug Therapy, Combination Female HIV HIV Infections - drug therapy HIV Infections - transmission HIV Infections - virology HIV-1 - drug effects Human immunodeficiency virus Humans Male Males Middle Aged Mortality Ribonucleic acid RNA Statistical analysis Therapy |
| title | Effectiveness of Transmitted Drug Resistance Testing Before Initiation of Antiretroviral Therapy in HIV-Positive Individuals |
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