Michael J Silverberg1, Wendy Leyden1, Raúl U Hernández-Ramírez2,3, Li Qin4, Haiqun Lin3,5, Amy C Justice4,6,7, Nancy A Hessol8, Chad J Achenbach9, Gypsyamber D'Souza10, Eric A Engels11, Keri N Althoff10, Angel M Mayor12, Timothy R Sterling13, Mari M Kitahata14, Ronald J Bosch15, Michael S Saag16, Charles S Rabkin11, Michael A Horberg17, M John Gill18, Surbhi Grover19, W Christopher Mathews20, Jun Li21, Heidi M Crane14, Stephen J Gange10, Bryan Lau10, Richard D Moore22, Robert Dubrow23, Romain S Neugebauer1. 1. Division of Research, Kaiser Permanente Northern California, Oakland, California, USA. 2. Department of Chronic Disease Epidemiology, Yale School of Public Health, Yale School of Medicine, New Haven, Connecticut, USA. 3. Department of Biostatistics, Yale School of Public Health, Yale School of Medicine, New Haven, Connecticut, USA. 4. Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut, USA. 5. School of Nursing, Rutgers Biomedical and Health Sciences, Rutgers University, Newark, New Jersey, USA. 6. Department of Health Policy and Management, Yale School of Public Health, Yale School of Medicine, New Haven, Connecticut, USA. 7. Research Service, Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut, USA. 8. Department of Clinical Pharmacy, University of California, San Francisco, San Francisco, California, USA. 9. Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA. 10. Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA. 11. Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland, USA. 12. Retrovirus Research Center, Universidad Central del Caribe School of Medicine, Bayamon, Puerto Rico. 13. Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA. 14. Department of Medicine, University of Washington, Seattle, Washington, USA. 15. Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA. 16. Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA. 17. Mid-Atlantic Permanente Research Institute, Kaiser Permanente Mid-Atlantic States, Rockville, Maryland, USA. 18. Department of Medicine, University of Calgary, Calgary, Alberta, Canada. 19. Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA. 20. Department of Medicine, University of California San Diego, San Diego, California, USA. 21. Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia, USA. 22. Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. 23. Department of Environmental Health Sciences, Yale School of Public Health, Yale School of Medicine, New Haven, Connecticut, USA.
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.
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.
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