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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Published inClinical infectious diseases Vol. 72; no. 11; pp. 1900 - 1909
Main Authors 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
Format Journal Article
LanguageEnglish
Published US Oxford University Press 01.06.2021
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
epidemiology
cancer
HIV
causal inference
antiretroviral therapy
Online AccessGet full text
ISSN1058-4838
1537-6591
1537-6591
DOI10.1093/cid/ciaa1046

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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.
AbstractList 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). 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. 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). 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.
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).BACKGROUNDPersons 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).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.METHODSWe 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.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).RESULTSProtective 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).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.CONCLUSIONSEarlier 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.
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.
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.
Author Dubrow, Robert
Grover, Surbhi
Mathews, W Christopher
Kitahata, Mari M
Moore, Richard D
Crane, Heidi M
Gange, Stephen J
Hessol, Nancy A
Hernández-Ramírez, Raúl U
Leyden, Wendy
Engels, Eric A
Horberg, Michael A
Althoff, Keri N
Silverberg, Michael J
Bosch, Ronald J
Gill, M John
Lau, Bryan
Qin, Li
Mayor, Angel M
Li, Jun
Saag, Michael S
Lin, Haiqun
Justice, Amy C
Achenbach, Chad J
Sterling, Timothy R
D’Souza, Gypsyamber
Neugebauer, Romain S
Rabkin, Charles S
AuthorAffiliation 23 Department of Environmental Health Sciences, Yale School of Public Health, Yale School of Medicine , New Haven, Connecticut , USA
16 Department of Medicine, University of Alabama at Birmingham , Birmingham, Alabama , USA
9 Division of Infectious Diseases, Northwestern University Feinberg School of Medicine , Chicago, Illinois , USA
22 Department of Medicine, Johns Hopkins University School of Medicine , Baltimore, Maryland , USA
12 Retrovirus Research Center, Universidad Central del Caribe School of Medicine , Bayamon , Puerto Rico
1 Division of Research, Kaiser Permanente Northern California , Oakland, California , USA
5 School of Nursing, Rutgers Biomedical and Health Sciences, Rutgers University , Newark, New Jersey , USA
15 Department of Biostatistics, Harvard T.H. Chan School of Public Health , Boston, Massachusetts , USA
13 Department of Medicine, Vanderbilt University Medical Center , Nashville, Tennessee , USA
18 Department of Medicine, University of Calgary , Calgary, Alberta , Cana
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Copyright_xml – notice: 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
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Issue 11
Keywords epidemiology
cancer
HIV
causal inference
antiretroviral therapy
Language English
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Snippet Abstract Background Persons living with human immunodeficiency virus (HIV; PLWH) experience a high burden of cancer. It remains unknown which cancer types are...
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 antiretroviral therapy initiation has potential to reduce the burden of virus-related cancers in people living with Human Immunodeficiency Virus, but...
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SubjectTerms 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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