The Effect of Interrupted/Deferred Antiretroviral Therapy on Disease Risk: A SMART and START Combined Analysis
By pooling SMART/START data, we found that a randomized strategy of interrupted/deferred antiretroviral therapy increases the hazard of AIDS by 3.6, serious non-AIDS (SNA) by 1.6, and the composite of AIDS, SNA, or death by 2.1. Abstract Background Pooled data from the SMART and START trials were us...
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| Veröffentlicht in: | The Journal of infectious diseases 2019-01, Vol.219 (2), p.254-263 |
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| creator | Borges, Álvaro H Neuhaus, Jacqueline Sharma, Shweta Neaton, James D Henry, Keith Anagnostou, Olga Staub, Teresa Emery, Sean Lundgren, Jens D |
| description | By pooling SMART/START data, we found that a randomized strategy of interrupted/deferred antiretroviral therapy increases the hazard of AIDS by 3.6, serious non-AIDS (SNA) by 1.6, and the composite of AIDS, SNA, or death by 2.1.
Abstract
Background
Pooled data from the SMART and START trials were used to compare deferred/intermittent versus immediate/continuous antiretroviral therapy (ART) on disease risk.
Methods
Endpoints assessed were AIDS, serious non-AIDS (SNA), cardiovascular disease (CVD), cancer, and death. Pooled (stratified by study) hazard ratios (HRs) from Cox models were obtained for deferred/intermittent ART versus immediate/continuous ART; analyses were conducted to assess consistency of HRs across baseline-defined subgroups.
Results
Among 10156 participants, there were 124 AIDS, 247 SNA, 117 cancers, 103 CVD, and 120 deaths. Interventions in each trial led to similar differences in CD4 count and viral suppression. Pooled HRs (95% confidence interval) of deferred/intermittent ART versus immediate/continuous ART were for AIDS 3.63 (2.37–5.56); SNA 1.62 (1.25–2.09); CVD 1.59 (1.07–2.37); cancer 1.93 (1.32–2.83); and death 1.80 (1.24–2.61). Underlying risk was greater in SMART than START. Given the similar HRs for each trial, absolute risk differences between treatment groups were greater in SMART than START. Pooled HRs were similar across subgroups.
Conclusions
Treatment group differences in CD4 count and viral suppression were similar in SMART and START. Likely as a consequence, relative differences in risk of AIDS and SNA between immediate/continuous ART and deferred/intermittent ART were similar.
Clinical Trials Registration
NCT00027352 and NCT00867048. |
| doi_str_mv | 10.1093/infdis/jiy442 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6306018</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><oup_id>10.1093/infdis/jiy442</oup_id><sourcerecordid>2447808141</sourcerecordid><originalsourceid>FETCH-LOGICAL-c448t-b713fad3a20dd797db4791d2d1d9a169450f6150706dc659dd0e87a69466af573</originalsourceid><addsrcrecordid>eNqFkc9rFDEYhoModq0evUrAi5fpfvkxyYwHYdnWWmgR2vUcspPEZp1NpslMYf97026t1ktP-eB78vB-vAi9J3BEoGVzH5zxeb7xO87pCzQjNZOVEIS9RDMASivStO0BepPzBgA4E_I1OmAAjBJJZiisri0-cc52I44On4XRpjQNozXzY-vKbA1ehNEnO6Z465PucfmR9LDDMeBjn63OFl_6_OszXuCri8XlCutg8NXqblrG7dqHe4Xud9nnt-iV03227x7eQ_Tj68lq-a06_356tlycVx3nzVitJWFOG6YpGCNbadZctsRQQ0yriWh5DU6QGiQI04m6NQZsI3VZCKFdLdkh-rL3DtN6a01nw1iiqyH5rU47FbVXTzfBX6uf8VYJBgJIUwSfHgQp3kw2j2rrc2f7Xgcbp6woSE4orWso6Mf_0E2cUjm4UJzLBhrCSaGqPdWlmHOy7jEMAXXXpNo3qfZNFv7Dvxc80n-q-5swTsMzrt_Yiqkd</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2447808141</pqid></control><display><type>article</type><title>The Effect of Interrupted/Deferred Antiretroviral Therapy on Disease Risk: A SMART and START Combined Analysis</title><source>MEDLINE</source><source>Oxford University Press Journals All Titles (1996-Current)</source><source>Alma/SFX Local Collection</source><creator>Borges, Álvaro H ; Neuhaus, Jacqueline ; Sharma, Shweta ; Neaton, James D ; Henry, Keith ; Anagnostou, Olga ; Staub, Teresa ; Emery, Sean ; Lundgren, Jens D</creator><creatorcontrib>Borges, Álvaro H ; Neuhaus, Jacqueline ; Sharma, Shweta ; Neaton, James D ; Henry, Keith ; Anagnostou, Olga ; Staub, Teresa ; Emery, Sean ; Lundgren, Jens D ; START Study Groups ; INSIGHT SMART ; START Study Groups ; INSIGHT SMART</creatorcontrib><description>By pooling SMART/START data, we found that a randomized strategy of interrupted/deferred antiretroviral therapy increases the hazard of AIDS by 3.6, serious non-AIDS (SNA) by 1.6, and the composite of AIDS, SNA, or death by 2.1.
Abstract
Background
Pooled data from the SMART and START trials were used to compare deferred/intermittent versus immediate/continuous antiretroviral therapy (ART) on disease risk.
Methods
Endpoints assessed were AIDS, serious non-AIDS (SNA), cardiovascular disease (CVD), cancer, and death. Pooled (stratified by study) hazard ratios (HRs) from Cox models were obtained for deferred/intermittent ART versus immediate/continuous ART; analyses were conducted to assess consistency of HRs across baseline-defined subgroups.
Results
Among 10156 participants, there were 124 AIDS, 247 SNA, 117 cancers, 103 CVD, and 120 deaths. Interventions in each trial led to similar differences in CD4 count and viral suppression. Pooled HRs (95% confidence interval) of deferred/intermittent ART versus immediate/continuous ART were for AIDS 3.63 (2.37–5.56); SNA 1.62 (1.25–2.09); CVD 1.59 (1.07–2.37); cancer 1.93 (1.32–2.83); and death 1.80 (1.24–2.61). Underlying risk was greater in SMART than START. Given the similar HRs for each trial, absolute risk differences between treatment groups were greater in SMART than START. Pooled HRs were similar across subgroups.
Conclusions
Treatment group differences in CD4 count and viral suppression were similar in SMART and START. Likely as a consequence, relative differences in risk of AIDS and SNA between immediate/continuous ART and deferred/intermittent ART were similar.
Clinical Trials Registration
NCT00027352 and NCT00867048.</description><identifier>ISSN: 0022-1899</identifier><identifier>EISSN: 1537-6613</identifier><identifier>DOI: 10.1093/infdis/jiy442</identifier><identifier>PMID: 30032171</identifier><language>eng</language><publisher>US: Oxford University Press</publisher><subject>Acquired Immunodeficiency Syndrome - drug therapy ; Adult ; Anti-HIV Agents - therapeutic use ; Anti-Retroviral Agents - therapeutic use ; Antiretroviral drugs ; Antiretroviral therapy ; Cardiovascular diseases ; Cardiovascular Diseases - drug therapy ; CD4 antigen ; CD4 Lymphocyte Count ; Clinical trials ; Disease Susceptibility ; Drug therapy ; Editor's Choice ; Female ; HIV ; HIV Infections - drug therapy ; HIV-1 ; Human immunodeficiency virus ; Humans ; Major and Brief Reports ; Male ; Middle Aged ; Neoplasms ; Proportional Hazards Models ; Time-to-Treatment ; Treatment Outcome</subject><ispartof>The Journal of infectious diseases, 2019-01, Vol.219 (2), p.254-263</ispartof><rights>The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com. 2018</rights><rights>The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c448t-b713fad3a20dd797db4791d2d1d9a169450f6150706dc659dd0e87a69466af573</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,1584,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30032171$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Borges, Álvaro H</creatorcontrib><creatorcontrib>Neuhaus, Jacqueline</creatorcontrib><creatorcontrib>Sharma, Shweta</creatorcontrib><creatorcontrib>Neaton, James D</creatorcontrib><creatorcontrib>Henry, Keith</creatorcontrib><creatorcontrib>Anagnostou, Olga</creatorcontrib><creatorcontrib>Staub, Teresa</creatorcontrib><creatorcontrib>Emery, Sean</creatorcontrib><creatorcontrib>Lundgren, Jens D</creatorcontrib><creatorcontrib>START Study Groups</creatorcontrib><creatorcontrib>INSIGHT SMART</creatorcontrib><creatorcontrib>START Study Groups</creatorcontrib><creatorcontrib>INSIGHT SMART</creatorcontrib><title>The Effect of Interrupted/Deferred Antiretroviral Therapy on Disease Risk: A SMART and START Combined Analysis</title><title>The Journal of infectious diseases</title><addtitle>J Infect Dis</addtitle><description>By pooling SMART/START data, we found that a randomized strategy of interrupted/deferred antiretroviral therapy increases the hazard of AIDS by 3.6, serious non-AIDS (SNA) by 1.6, and the composite of AIDS, SNA, or death by 2.1.
Abstract
Background
Pooled data from the SMART and START trials were used to compare deferred/intermittent versus immediate/continuous antiretroviral therapy (ART) on disease risk.
Methods
Endpoints assessed were AIDS, serious non-AIDS (SNA), cardiovascular disease (CVD), cancer, and death. Pooled (stratified by study) hazard ratios (HRs) from Cox models were obtained for deferred/intermittent ART versus immediate/continuous ART; analyses were conducted to assess consistency of HRs across baseline-defined subgroups.
Results
Among 10156 participants, there were 124 AIDS, 247 SNA, 117 cancers, 103 CVD, and 120 deaths. Interventions in each trial led to similar differences in CD4 count and viral suppression. Pooled HRs (95% confidence interval) of deferred/intermittent ART versus immediate/continuous ART were for AIDS 3.63 (2.37–5.56); SNA 1.62 (1.25–2.09); CVD 1.59 (1.07–2.37); cancer 1.93 (1.32–2.83); and death 1.80 (1.24–2.61). Underlying risk was greater in SMART than START. Given the similar HRs for each trial, absolute risk differences between treatment groups were greater in SMART than START. Pooled HRs were similar across subgroups.
Conclusions
Treatment group differences in CD4 count and viral suppression were similar in SMART and START. Likely as a consequence, relative differences in risk of AIDS and SNA between immediate/continuous ART and deferred/intermittent ART were similar.
Clinical Trials Registration
NCT00027352 and NCT00867048.</description><subject>Acquired Immunodeficiency Syndrome - drug therapy</subject><subject>Adult</subject><subject>Anti-HIV Agents - therapeutic use</subject><subject>Anti-Retroviral Agents - therapeutic use</subject><subject>Antiretroviral drugs</subject><subject>Antiretroviral therapy</subject><subject>Cardiovascular diseases</subject><subject>Cardiovascular Diseases - drug therapy</subject><subject>CD4 antigen</subject><subject>CD4 Lymphocyte Count</subject><subject>Clinical trials</subject><subject>Disease Susceptibility</subject><subject>Drug therapy</subject><subject>Editor's Choice</subject><subject>Female</subject><subject>HIV</subject><subject>HIV Infections - drug therapy</subject><subject>HIV-1</subject><subject>Human immunodeficiency virus</subject><subject>Humans</subject><subject>Major and Brief Reports</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Neoplasms</subject><subject>Proportional Hazards Models</subject><subject>Time-to-Treatment</subject><subject>Treatment Outcome</subject><issn>0022-1899</issn><issn>1537-6613</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc9rFDEYhoModq0evUrAi5fpfvkxyYwHYdnWWmgR2vUcspPEZp1NpslMYf97026t1ktP-eB78vB-vAi9J3BEoGVzH5zxeb7xO87pCzQjNZOVEIS9RDMASivStO0BepPzBgA4E_I1OmAAjBJJZiisri0-cc52I44On4XRpjQNozXzY-vKbA1ehNEnO6Z465PucfmR9LDDMeBjn63OFl_6_OszXuCri8XlCutg8NXqblrG7dqHe4Xud9nnt-iV03227x7eQ_Tj68lq-a06_356tlycVx3nzVitJWFOG6YpGCNbadZctsRQQ0yriWh5DU6QGiQI04m6NQZsI3VZCKFdLdkh-rL3DtN6a01nw1iiqyH5rU47FbVXTzfBX6uf8VYJBgJIUwSfHgQp3kw2j2rrc2f7Xgcbp6woSE4orWso6Mf_0E2cUjm4UJzLBhrCSaGqPdWlmHOy7jEMAXXXpNo3qfZNFv7Dvxc80n-q-5swTsMzrt_Yiqkd</recordid><startdate>20190107</startdate><enddate>20190107</enddate><creator>Borges, Álvaro H</creator><creator>Neuhaus, Jacqueline</creator><creator>Sharma, Shweta</creator><creator>Neaton, James D</creator><creator>Henry, Keith</creator><creator>Anagnostou, Olga</creator><creator>Staub, Teresa</creator><creator>Emery, Sean</creator><creator>Lundgren, Jens D</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>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20190107</creationdate><title>The Effect of Interrupted/Deferred Antiretroviral Therapy on Disease Risk: A SMART and START Combined Analysis</title><author>Borges, Álvaro H ; Neuhaus, Jacqueline ; Sharma, Shweta ; Neaton, James D ; Henry, Keith ; Anagnostou, Olga ; Staub, Teresa ; Emery, Sean ; Lundgren, Jens D</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c448t-b713fad3a20dd797db4791d2d1d9a169450f6150706dc659dd0e87a69466af573</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Acquired Immunodeficiency Syndrome - drug therapy</topic><topic>Adult</topic><topic>Anti-HIV Agents - therapeutic use</topic><topic>Anti-Retroviral Agents - therapeutic use</topic><topic>Antiretroviral drugs</topic><topic>Antiretroviral therapy</topic><topic>Cardiovascular diseases</topic><topic>Cardiovascular Diseases - drug therapy</topic><topic>CD4 antigen</topic><topic>CD4 Lymphocyte Count</topic><topic>Clinical trials</topic><topic>Disease Susceptibility</topic><topic>Drug therapy</topic><topic>Editor's Choice</topic><topic>Female</topic><topic>HIV</topic><topic>HIV Infections - drug therapy</topic><topic>HIV-1</topic><topic>Human immunodeficiency virus</topic><topic>Humans</topic><topic>Major and Brief Reports</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Neoplasms</topic><topic>Proportional Hazards Models</topic><topic>Time-to-Treatment</topic><topic>Treatment Outcome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Borges, Álvaro H</creatorcontrib><creatorcontrib>Neuhaus, Jacqueline</creatorcontrib><creatorcontrib>Sharma, Shweta</creatorcontrib><creatorcontrib>Neaton, James D</creatorcontrib><creatorcontrib>Henry, Keith</creatorcontrib><creatorcontrib>Anagnostou, Olga</creatorcontrib><creatorcontrib>Staub, Teresa</creatorcontrib><creatorcontrib>Emery, Sean</creatorcontrib><creatorcontrib>Lundgren, Jens D</creatorcontrib><creatorcontrib>START Study Groups</creatorcontrib><creatorcontrib>INSIGHT SMART</creatorcontrib><creatorcontrib>START Study Groups</creatorcontrib><creatorcontrib>INSIGHT SMART</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of infectious diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Borges, Álvaro H</au><au>Neuhaus, Jacqueline</au><au>Sharma, Shweta</au><au>Neaton, James D</au><au>Henry, Keith</au><au>Anagnostou, Olga</au><au>Staub, Teresa</au><au>Emery, Sean</au><au>Lundgren, Jens D</au><aucorp>START Study Groups</aucorp><aucorp>INSIGHT SMART</aucorp><aucorp>START Study Groups</aucorp><aucorp>INSIGHT SMART</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Effect of Interrupted/Deferred Antiretroviral Therapy on Disease Risk: A SMART and START Combined Analysis</atitle><jtitle>The Journal of infectious diseases</jtitle><addtitle>J Infect Dis</addtitle><date>2019-01-07</date><risdate>2019</risdate><volume>219</volume><issue>2</issue><spage>254</spage><epage>263</epage><pages>254-263</pages><issn>0022-1899</issn><eissn>1537-6613</eissn><abstract>By pooling SMART/START data, we found that a randomized strategy of interrupted/deferred antiretroviral therapy increases the hazard of AIDS by 3.6, serious non-AIDS (SNA) by 1.6, and the composite of AIDS, SNA, or death by 2.1.
Abstract
Background
Pooled data from the SMART and START trials were used to compare deferred/intermittent versus immediate/continuous antiretroviral therapy (ART) on disease risk.
Methods
Endpoints assessed were AIDS, serious non-AIDS (SNA), cardiovascular disease (CVD), cancer, and death. Pooled (stratified by study) hazard ratios (HRs) from Cox models were obtained for deferred/intermittent ART versus immediate/continuous ART; analyses were conducted to assess consistency of HRs across baseline-defined subgroups.
Results
Among 10156 participants, there were 124 AIDS, 247 SNA, 117 cancers, 103 CVD, and 120 deaths. Interventions in each trial led to similar differences in CD4 count and viral suppression. Pooled HRs (95% confidence interval) of deferred/intermittent ART versus immediate/continuous ART were for AIDS 3.63 (2.37–5.56); SNA 1.62 (1.25–2.09); CVD 1.59 (1.07–2.37); cancer 1.93 (1.32–2.83); and death 1.80 (1.24–2.61). Underlying risk was greater in SMART than START. Given the similar HRs for each trial, absolute risk differences between treatment groups were greater in SMART than START. Pooled HRs were similar across subgroups.
Conclusions
Treatment group differences in CD4 count and viral suppression were similar in SMART and START. Likely as a consequence, relative differences in risk of AIDS and SNA between immediate/continuous ART and deferred/intermittent ART were similar.
Clinical Trials Registration
NCT00027352 and NCT00867048.</abstract><cop>US</cop><pub>Oxford University Press</pub><pmid>30032171</pmid><doi>10.1093/infdis/jiy442</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Oxford University Press Journals All Titles (1996-Current); Alma/SFX Local Collection |
| subjects | Acquired Immunodeficiency Syndrome - drug therapy Adult Anti-HIV Agents - therapeutic use Anti-Retroviral Agents - therapeutic use Antiretroviral drugs Antiretroviral therapy Cardiovascular diseases Cardiovascular Diseases - drug therapy CD4 antigen CD4 Lymphocyte Count Clinical trials Disease Susceptibility Drug therapy Editor's Choice Female HIV HIV Infections - drug therapy HIV-1 Human immunodeficiency virus Humans Major and Brief Reports Male Middle Aged Neoplasms Proportional Hazards Models Time-to-Treatment Treatment Outcome |
| title | The Effect of Interrupted/Deferred Antiretroviral Therapy on Disease Risk: A SMART and START Combined Analysis |
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