Timing of Antiretroviral Therapy Initiation and Risk of Cancer Among Persons Living With Human Immunodeficiency Virus
Abstract Background Persons living with human immunodeficiency virus (HIV; PLWH) experience a high burden of cancer. It remains unknown which cancer types are reduced in PLWH with earlier initiation of antiretroviral therapy (ART). Methods We evaluated AIDS-free, ART-naive PLWH during 1996–2014 from...
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| Veröffentlicht in: | Clinical infectious diseases 2021-06, Vol.72 (11), p.1900-1909 |
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| creator | Silverberg, Michael J Leyden, Wendy Hernández-Ramírez, Raúl U Qin, Li Lin, Haiqun Justice, Amy C Hessol, Nancy A Achenbach, Chad J D’Souza, Gypsyamber Engels, Eric A Althoff, Keri N Mayor, Angel M Sterling, Timothy R Kitahata, Mari M Bosch, Ronald J Saag, Michael S Rabkin, Charles S Horberg, Michael A Gill, M John Grover, Surbhi Mathews, W Christopher Li, Jun Crane, Heidi M Gange, Stephen J Lau, Bryan Moore, Richard D Dubrow, Robert Neugebauer, Romain S |
| description | Abstract
Background
Persons living with human immunodeficiency virus (HIV; PLWH) experience a high burden of cancer. It remains unknown which cancer types are reduced in PLWH with earlier initiation of antiretroviral therapy (ART).
Methods
We evaluated AIDS-free, ART-naive PLWH during 1996–2014 from 22 cohorts participating in the North American AIDS Cohort Collaboration on Research and Design. PLWH were followed from first observed CD4 of 350–500 cells/µL (baseline) until incident cancer, death, lost-to-follow-up, or December 2014. Outcomes included 6 cancer groups and 5 individual cancers that were confirmed by chart review or cancer registry linkage. We evaluated the effect of earlier (in the first 6 months after baseline) versus deferred ART initiation on cancer risk. Marginal structural models were used with inverse probability weighting to account for time-dependent confounding and informative right-censoring, with weights informed by subject’s age, sex, cohort, baseline year, race/ethnicity, HIV transmission risk, smoking, viral hepatitis, CD4, and AIDS diagnoses.
Results
Protective results for earlier ART were found for any cancer (adjusted hazard ratio [HR] 0.57; 95% confidence interval [CI], .37–.86), AIDS-defining cancers (HR 0.23; 95% CI, .11–.49), any virus-related cancer (HR 0.30; 95% CI, .16–.54), Kaposi sarcoma (HR 0.25; 95% CI, .10–.61), and non-Hodgkin lymphoma (HR 0.22; 95% CI, .06–.73). By 15 years, there was also an observed reduced risk with earlier ART for virus-related NADCs (0.6% vs 2.3%; adjusted risk difference −1.6; 95% CI, −2.8, −.5).
Conclusions
Earlier ART initiation has potential to reduce the burden of virus-related cancers in PLWH but not non-AIDS-defining cancers (NADCs) without known or suspected viral etiology.
Earlier antiretroviral therapy initiation has potential to reduce the burden of virus-related cancers in people living with Human Immunodeficiency Virus, but not cancers without known or suspected viral etiology. |
| doi_str_mv | 10.1093/cid/ciaa1046 |
| format | Article |
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Background
Persons living with human immunodeficiency virus (HIV; PLWH) experience a high burden of cancer. It remains unknown which cancer types are reduced in PLWH with earlier initiation of antiretroviral therapy (ART).
Methods
We evaluated AIDS-free, ART-naive PLWH during 1996–2014 from 22 cohorts participating in the North American AIDS Cohort Collaboration on Research and Design. PLWH were followed from first observed CD4 of 350–500 cells/µL (baseline) until incident cancer, death, lost-to-follow-up, or December 2014. Outcomes included 6 cancer groups and 5 individual cancers that were confirmed by chart review or cancer registry linkage. We evaluated the effect of earlier (in the first 6 months after baseline) versus deferred ART initiation on cancer risk. Marginal structural models were used with inverse probability weighting to account for time-dependent confounding and informative right-censoring, with weights informed by subject’s age, sex, cohort, baseline year, race/ethnicity, HIV transmission risk, smoking, viral hepatitis, CD4, and AIDS diagnoses.
Results
Protective results for earlier ART were found for any cancer (adjusted hazard ratio [HR] 0.57; 95% confidence interval [CI], .37–.86), AIDS-defining cancers (HR 0.23; 95% CI, .11–.49), any virus-related cancer (HR 0.30; 95% CI, .16–.54), Kaposi sarcoma (HR 0.25; 95% CI, .10–.61), and non-Hodgkin lymphoma (HR 0.22; 95% CI, .06–.73). By 15 years, there was also an observed reduced risk with earlier ART for virus-related NADCs (0.6% vs 2.3%; adjusted risk difference −1.6; 95% CI, −2.8, −.5).
Conclusions
Earlier ART initiation has potential to reduce the burden of virus-related cancers in PLWH but not non-AIDS-defining cancers (NADCs) without known or suspected viral etiology.
Earlier antiretroviral therapy initiation has potential to reduce the burden of virus-related cancers in people living with Human Immunodeficiency Virus, but not cancers without known or suspected viral etiology.</description><identifier>ISSN: 1058-4838</identifier><identifier>EISSN: 1537-6591</identifier><identifier>DOI: 10.1093/cid/ciaa1046</identifier><identifier>PMID: 32785640</identifier><language>eng</language><publisher>US: Oxford University Press</publisher><subject>Acquired Immunodeficiency Syndrome ; CD4 Lymphocyte Count ; HIV ; HIV Infections - complications ; HIV Infections - drug therapy ; HIV Infections - epidemiology ; Humans ; Major and Commentaries ; Neoplasms - epidemiology ; Sarcoma, Kaposi</subject><ispartof>Clinical infectious diseases, 2021-06, Vol.72 (11), p.1900-1909</ispartof><rights>The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com. 2020</rights><rights>The Author(s) 2020. 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-c416t-7b91950e6b20bff447b8486ae9abee43a31ade99db52d8a3e14060e32e9c24d73</citedby><cites>FETCH-LOGICAL-c416t-7b91950e6b20bff447b8486ae9abee43a31ade99db52d8a3e14060e32e9c24d73</cites><orcidid>0000-0002-2355-612X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,1584,27923,27924</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32785640$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Silverberg, Michael J</creatorcontrib><creatorcontrib>Leyden, Wendy</creatorcontrib><creatorcontrib>Hernández-Ramírez, Raúl U</creatorcontrib><creatorcontrib>Qin, Li</creatorcontrib><creatorcontrib>Lin, Haiqun</creatorcontrib><creatorcontrib>Justice, Amy C</creatorcontrib><creatorcontrib>Hessol, Nancy A</creatorcontrib><creatorcontrib>Achenbach, Chad J</creatorcontrib><creatorcontrib>D’Souza, Gypsyamber</creatorcontrib><creatorcontrib>Engels, Eric A</creatorcontrib><creatorcontrib>Althoff, Keri N</creatorcontrib><creatorcontrib>Mayor, Angel M</creatorcontrib><creatorcontrib>Sterling, Timothy R</creatorcontrib><creatorcontrib>Kitahata, Mari M</creatorcontrib><creatorcontrib>Bosch, Ronald J</creatorcontrib><creatorcontrib>Saag, Michael S</creatorcontrib><creatorcontrib>Rabkin, Charles S</creatorcontrib><creatorcontrib>Horberg, Michael A</creatorcontrib><creatorcontrib>Gill, M John</creatorcontrib><creatorcontrib>Grover, Surbhi</creatorcontrib><creatorcontrib>Mathews, W Christopher</creatorcontrib><creatorcontrib>Li, Jun</creatorcontrib><creatorcontrib>Crane, Heidi M</creatorcontrib><creatorcontrib>Gange, Stephen J</creatorcontrib><creatorcontrib>Lau, Bryan</creatorcontrib><creatorcontrib>Moore, Richard D</creatorcontrib><creatorcontrib>Dubrow, Robert</creatorcontrib><creatorcontrib>Neugebauer, Romain S</creatorcontrib><title>Timing of Antiretroviral Therapy Initiation and Risk of Cancer Among Persons Living With Human Immunodeficiency Virus</title><title>Clinical infectious diseases</title><addtitle>Clin Infect Dis</addtitle><description>Abstract
Background
Persons living with human immunodeficiency virus (HIV; PLWH) experience a high burden of cancer. It remains unknown which cancer types are reduced in PLWH with earlier initiation of antiretroviral therapy (ART).
Methods
We evaluated AIDS-free, ART-naive PLWH during 1996–2014 from 22 cohorts participating in the North American AIDS Cohort Collaboration on Research and Design. PLWH were followed from first observed CD4 of 350–500 cells/µL (baseline) until incident cancer, death, lost-to-follow-up, or December 2014. Outcomes included 6 cancer groups and 5 individual cancers that were confirmed by chart review or cancer registry linkage. We evaluated the effect of earlier (in the first 6 months after baseline) versus deferred ART initiation on cancer risk. Marginal structural models were used with inverse probability weighting to account for time-dependent confounding and informative right-censoring, with weights informed by subject’s age, sex, cohort, baseline year, race/ethnicity, HIV transmission risk, smoking, viral hepatitis, CD4, and AIDS diagnoses.
Results
Protective results for earlier ART were found for any cancer (adjusted hazard ratio [HR] 0.57; 95% confidence interval [CI], .37–.86), AIDS-defining cancers (HR 0.23; 95% CI, .11–.49), any virus-related cancer (HR 0.30; 95% CI, .16–.54), Kaposi sarcoma (HR 0.25; 95% CI, .10–.61), and non-Hodgkin lymphoma (HR 0.22; 95% CI, .06–.73). By 15 years, there was also an observed reduced risk with earlier ART for virus-related NADCs (0.6% vs 2.3%; adjusted risk difference −1.6; 95% CI, −2.8, −.5).
Conclusions
Earlier ART initiation has potential to reduce the burden of virus-related cancers in PLWH but not non-AIDS-defining cancers (NADCs) without known or suspected viral etiology.
Earlier antiretroviral therapy initiation has potential to reduce the burden of virus-related cancers in people living with Human Immunodeficiency Virus, but not cancers without known or suspected viral etiology.</description><subject>Acquired Immunodeficiency Syndrome</subject><subject>CD4 Lymphocyte Count</subject><subject>HIV</subject><subject>HIV Infections - complications</subject><subject>HIV Infections - drug therapy</subject><subject>HIV Infections - epidemiology</subject><subject>Humans</subject><subject>Major and Commentaries</subject><subject>Neoplasms - epidemiology</subject><subject>Sarcoma, Kaposi</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>eNp9kMFLwzAUh4Mobk5vniU3L1aTJm3TizCGusFAkanHkrav29M1GUk72H9vx9zQi4eQQL7f93g_Qi45u-UsFXcFlt3RmjMZH5E-j0QSxFHKj7s3i1QglVA9cub9J2OcKxadkp4IExXFkvVJO8MazZzaig5Ngw4aZ9fo9JLOFuD0akMnBhvUDVpDtSnpK_qvLT3SpgBHh7Xt0i_gvDWeTnG9lX1gs6DjttaGTuq6NbaECgsEU2zoO7rWn5OTSi89XPzcA_L2-DAbjYPp89NkNJwGheRxEyR5ytOIQZyHLK8qKZNcSRVrSHUOIIUWXJeQpmUehaXSArhkMQMRQlqEskzEgNzvvKs2r6EswDTdatnKYa3dJrMas78_BhfZ3K4zJXjERdgJbnaCwlnvHVSHLGfZtv6sqz_b19_hV7_nHeB93x1wvQNsu_pf9Q37SpJm</recordid><startdate>20210601</startdate><enddate>20210601</enddate><creator>Silverberg, Michael J</creator><creator>Leyden, Wendy</creator><creator>Hernández-Ramírez, Raúl U</creator><creator>Qin, Li</creator><creator>Lin, Haiqun</creator><creator>Justice, Amy C</creator><creator>Hessol, Nancy A</creator><creator>Achenbach, Chad J</creator><creator>D’Souza, Gypsyamber</creator><creator>Engels, Eric A</creator><creator>Althoff, Keri N</creator><creator>Mayor, Angel M</creator><creator>Sterling, Timothy R</creator><creator>Kitahata, Mari M</creator><creator>Bosch, Ronald J</creator><creator>Saag, Michael S</creator><creator>Rabkin, Charles S</creator><creator>Horberg, Michael A</creator><creator>Gill, M John</creator><creator>Grover, Surbhi</creator><creator>Mathews, W Christopher</creator><creator>Li, Jun</creator><creator>Crane, Heidi M</creator><creator>Gange, Stephen J</creator><creator>Lau, Bryan</creator><creator>Moore, Richard D</creator><creator>Dubrow, Robert</creator><creator>Neugebauer, Romain S</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>5PM</scope><orcidid>https://orcid.org/0000-0002-2355-612X</orcidid></search><sort><creationdate>20210601</creationdate><title>Timing of Antiretroviral Therapy Initiation and Risk of Cancer Among Persons Living With Human Immunodeficiency Virus</title><author>Silverberg, Michael J ; Leyden, Wendy ; Hernández-Ramírez, Raúl U ; Qin, Li ; Lin, Haiqun ; Justice, Amy C ; Hessol, Nancy A ; Achenbach, Chad J ; D’Souza, Gypsyamber ; Engels, Eric A ; Althoff, Keri N ; Mayor, Angel M ; Sterling, Timothy R ; Kitahata, Mari M ; Bosch, Ronald J ; Saag, Michael S ; Rabkin, Charles S ; Horberg, Michael A ; Gill, M John ; Grover, Surbhi ; Mathews, W Christopher ; Li, Jun ; Crane, Heidi M ; Gange, Stephen J ; Lau, Bryan ; Moore, Richard D ; Dubrow, Robert ; Neugebauer, Romain S</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c416t-7b91950e6b20bff447b8486ae9abee43a31ade99db52d8a3e14060e32e9c24d73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Acquired Immunodeficiency Syndrome</topic><topic>CD4 Lymphocyte Count</topic><topic>HIV</topic><topic>HIV Infections - complications</topic><topic>HIV Infections - drug therapy</topic><topic>HIV Infections - epidemiology</topic><topic>Humans</topic><topic>Major and Commentaries</topic><topic>Neoplasms - epidemiology</topic><topic>Sarcoma, Kaposi</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Silverberg, Michael J</creatorcontrib><creatorcontrib>Leyden, Wendy</creatorcontrib><creatorcontrib>Hernández-Ramírez, Raúl U</creatorcontrib><creatorcontrib>Qin, Li</creatorcontrib><creatorcontrib>Lin, Haiqun</creatorcontrib><creatorcontrib>Justice, Amy C</creatorcontrib><creatorcontrib>Hessol, Nancy A</creatorcontrib><creatorcontrib>Achenbach, Chad J</creatorcontrib><creatorcontrib>D’Souza, Gypsyamber</creatorcontrib><creatorcontrib>Engels, Eric A</creatorcontrib><creatorcontrib>Althoff, Keri N</creatorcontrib><creatorcontrib>Mayor, Angel M</creatorcontrib><creatorcontrib>Sterling, Timothy R</creatorcontrib><creatorcontrib>Kitahata, Mari M</creatorcontrib><creatorcontrib>Bosch, Ronald J</creatorcontrib><creatorcontrib>Saag, Michael S</creatorcontrib><creatorcontrib>Rabkin, Charles S</creatorcontrib><creatorcontrib>Horberg, Michael A</creatorcontrib><creatorcontrib>Gill, M John</creatorcontrib><creatorcontrib>Grover, Surbhi</creatorcontrib><creatorcontrib>Mathews, W Christopher</creatorcontrib><creatorcontrib>Li, Jun</creatorcontrib><creatorcontrib>Crane, Heidi M</creatorcontrib><creatorcontrib>Gange, Stephen J</creatorcontrib><creatorcontrib>Lau, Bryan</creatorcontrib><creatorcontrib>Moore, Richard D</creatorcontrib><creatorcontrib>Dubrow, Robert</creatorcontrib><creatorcontrib>Neugebauer, Romain S</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</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>Silverberg, Michael J</au><au>Leyden, Wendy</au><au>Hernández-Ramírez, Raúl U</au><au>Qin, Li</au><au>Lin, Haiqun</au><au>Justice, Amy C</au><au>Hessol, Nancy A</au><au>Achenbach, Chad J</au><au>D’Souza, Gypsyamber</au><au>Engels, Eric A</au><au>Althoff, Keri N</au><au>Mayor, Angel M</au><au>Sterling, Timothy R</au><au>Kitahata, Mari M</au><au>Bosch, Ronald J</au><au>Saag, Michael S</au><au>Rabkin, Charles S</au><au>Horberg, Michael A</au><au>Gill, M John</au><au>Grover, Surbhi</au><au>Mathews, W Christopher</au><au>Li, Jun</au><au>Crane, Heidi M</au><au>Gange, Stephen J</au><au>Lau, Bryan</au><au>Moore, Richard D</au><au>Dubrow, Robert</au><au>Neugebauer, Romain S</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Timing of Antiretroviral Therapy Initiation and Risk of Cancer Among Persons Living With Human Immunodeficiency Virus</atitle><jtitle>Clinical infectious diseases</jtitle><addtitle>Clin Infect Dis</addtitle><date>2021-06-01</date><risdate>2021</risdate><volume>72</volume><issue>11</issue><spage>1900</spage><epage>1909</epage><pages>1900-1909</pages><issn>1058-4838</issn><eissn>1537-6591</eissn><abstract>Abstract
Background
Persons living with human immunodeficiency virus (HIV; PLWH) experience a high burden of cancer. It remains unknown which cancer types are reduced in PLWH with earlier initiation of antiretroviral therapy (ART).
Methods
We evaluated AIDS-free, ART-naive PLWH during 1996–2014 from 22 cohorts participating in the North American AIDS Cohort Collaboration on Research and Design. PLWH were followed from first observed CD4 of 350–500 cells/µL (baseline) until incident cancer, death, lost-to-follow-up, or December 2014. Outcomes included 6 cancer groups and 5 individual cancers that were confirmed by chart review or cancer registry linkage. We evaluated the effect of earlier (in the first 6 months after baseline) versus deferred ART initiation on cancer risk. Marginal structural models were used with inverse probability weighting to account for time-dependent confounding and informative right-censoring, with weights informed by subject’s age, sex, cohort, baseline year, race/ethnicity, HIV transmission risk, smoking, viral hepatitis, CD4, and AIDS diagnoses.
Results
Protective results for earlier ART were found for any cancer (adjusted hazard ratio [HR] 0.57; 95% confidence interval [CI], .37–.86), AIDS-defining cancers (HR 0.23; 95% CI, .11–.49), any virus-related cancer (HR 0.30; 95% CI, .16–.54), Kaposi sarcoma (HR 0.25; 95% CI, .10–.61), and non-Hodgkin lymphoma (HR 0.22; 95% CI, .06–.73). By 15 years, there was also an observed reduced risk with earlier ART for virus-related NADCs (0.6% vs 2.3%; adjusted risk difference −1.6; 95% CI, −2.8, −.5).
Conclusions
Earlier ART initiation has potential to reduce the burden of virus-related cancers in PLWH but not non-AIDS-defining cancers (NADCs) without known or suspected viral etiology.
Earlier antiretroviral therapy initiation has potential to reduce the burden of virus-related cancers in people living with Human Immunodeficiency Virus, but not cancers without known or suspected viral etiology.</abstract><cop>US</cop><pub>Oxford University Press</pub><pmid>32785640</pmid><doi>10.1093/cid/ciaa1046</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0002-2355-612X</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | Clinical infectious diseases, 2021-06, Vol.72 (11), p.1900-1909 |
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| source | MEDLINE; Oxford University Press Journals All Titles (1996-Current); EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Acquired Immunodeficiency Syndrome CD4 Lymphocyte Count HIV HIV Infections - complications HIV Infections - drug therapy HIV Infections - epidemiology Humans Major and Commentaries Neoplasms - epidemiology Sarcoma, Kaposi |
| title | Timing of Antiretroviral Therapy Initiation and Risk of Cancer Among Persons Living With Human Immunodeficiency Virus |
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