Álvaro H Borges1, Jacqueline Neuhaus2, Abdel G Babiker3, Keith Henry4, Mamta K Jain5, Adrian Palfreeman6, Peter Mugyenyi7, Pere Domingo8, Christian Hoffmann9,10, Tim R H Read11, Sanjay Pujari12, Michael Meulbroek13, Margaret Johnson14, Timothy Wilkin15, Ronald Mitsuyasu16. 1. Centre for Health and Infectious Diseases Research, Department of Infectious Diseases, Section 2100, Rigshospitalet, University of Copenhagen, Denmark. 2. Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis. 3. Medical Research Council Clinical Trials Unit, University College London, United Kingdom. 4. Hennepin County Medical Center, Minneapolis, Minnesota. 5. Division of Infectious Disease, UT Southwestern Medical Center, Dallas, Texas. 6. Department of Infectious Diseases, University Hospitals Leicester NHS Trust, Leicester, United Kingdom. 7. Joint Clinical Research Center, Kampala, Uganda. 8. Infectious Diseases Unit, Hospital de la Santa Creu i Sant Pau, Autonomous University of Barcelona and Red de Investigación en SIDA, Barcelona, Spain. 9. Infektionsmedizinisches Centrum Hamburg Study Center, Hamburg. 10. Department of Medicine II, University of Schleswig-Holstein, Kiel, Germany. 11. Melbourne Sexual Health Centre, Alfred Hospital and Central Clinical School, Monash University, Australia. 12. Institute of Infectious Diseases, Pune, Maharashtra, India. 13. Projecte dels Noms/Hispanosida, Barcelona, Spain. 14. Ian Charleson Day Centre, Royal Free Hospital, London, United Kingdom. 15. Division of Infectious Diseases, Weill Cornell Medicine, New York, New York. 16. Center for Clinical AIDS Research and Education, David Geffen School of Medicine, University of California, Los Angeles.
Abstract
BACKGROUND: In the Strategic Timing of Antiretroviral Treatment (START) study, immediate combination antiretroviral therapy (cART) initiation reduced cancer risk by 64%. We hypothesized that risk reduction was higher for infection-related cancer and determined by differences in CD4 cell counts and human immunodeficiency virus (HIV) RNA between the study arms. METHODS: Incident malignancies in START were categorized into infection-related and infection-unrelated cancer. We used Cox models to assess factors associated with both cancer categories. We used sequential adjustment for baseline covariates, cancer risk factors, and HIV-specific variables to investigate potential mediators of cancer risk reduction with immediate cART. RESULTS: There were 14 cancers among persons randomized to immediate cART (6 infection-related and 8 infection-unrelated) and 39 cancers in the deferred arm (23 infection-related and 16 infection-unrelated); hazard ratios of immediate vs deferred cART initiation were 0.26 (95% confidence interval [CI], .11-.64) for infection-related and 0.49 (95% CI, .21-1.15) for infection-unrelated cancer. Independent predictors of infection-related cancer were older age, higher body mass index, low- to middle-income region, HIV RNA, and baseline CD8 cell count. Older age and baseline CD8 cell count were independent predictors of infection-unrelated cancer. Adjustment for latest HIV RNA level had little impact on the protective effect of immediate cART on infection-related cancer. Adjustment for latest HIV RNA level, but not for CD4 cell count or cancer risk factors, attenuated the effect of immediate cART on infection-unrelated cancer. CONCLUSIONS:Immediate cART initiation significantly reduces risk of cancer. Although limited by small sample size, this benefit does not appear to be solely attributable to HIV RNA suppression and may be also mediated by other mechanisms.
RCT Entities:
BACKGROUND: In the Strategic Timing of Antiretroviral Treatment (START) study, immediate combination antiretroviral therapy (cART) initiation reduced cancer risk by 64%. We hypothesized that risk reduction was higher for infection-related cancer and determined by differences in CD4 cell counts and human immunodeficiency virus (HIV) RNA between the study arms. METHODS: Incident malignancies in START were categorized into infection-related and infection-unrelated cancer. We used Cox models to assess factors associated with both cancer categories. We used sequential adjustment for baseline covariates, cancer risk factors, and HIV-specific variables to investigate potential mediators of cancer risk reduction with immediate cART. RESULTS: There were 14 cancers among persons randomized to immediate cART (6 infection-related and 8 infection-unrelated) and 39 cancers in the deferred arm (23 infection-related and 16 infection-unrelated); hazard ratios of immediate vs deferred cART initiation were 0.26 (95% confidence interval [CI], .11-.64) for infection-related and 0.49 (95% CI, .21-1.15) for infection-unrelated cancer. Independent predictors of infection-related cancer were older age, higher body mass index, low- to middle-income region, HIV RNA, and baseline CD8 cell count. Older age and baseline CD8 cell count were independent predictors of infection-unrelated cancer. Adjustment for latest HIV RNA level had little impact on the protective effect of immediate cART on infection-related cancer. Adjustment for latest HIV RNA level, but not for CD4 cell count or cancer risk factors, attenuated the effect of immediate cART on infection-unrelated cancer. CONCLUSIONS: Immediate cART initiation significantly reduces risk of cancer. Although limited by small sample size, this benefit does not appear to be solely attributable to HIV RNA suppression and may be also mediated by other mechanisms.
Authors: Colette J Smith; Lene Ryom; Rainer Weber; Philippe Morlat; Christian Pradier; Peter Reiss; Justyna D Kowalska; Stephane de Wit; Matthew Law; Wafaa el Sadr; Ole Kirk; Nina Friis-Moller; Antonella d'Arminio Monforte; Andrew N Phillips; Caroline A Sabin; Jens D Lundgren Journal: Lancet Date: 2014-07-19 Impact factor: 79.321
Authors: Marie Helleberg; Jan Gerstoft; Shoaib Afzal; Gitte Kronborg; Carsten S Larsen; Court Pedersen; Stig E Bojesen; Børge G Nordestgaard; Niels Obel Journal: AIDS Date: 2014-06-19 Impact factor: 4.177
Authors: Jens D Lundgren; Abdel G Babiker; Fred Gordin; Sean Emery; Birgit Grund; Shweta Sharma; Anchalee Avihingsanon; David A Cooper; Gerd Fätkenheuer; Josep M Llibre; Jean-Michel Molina; Paula Munderi; Mauro Schechter; Robin Wood; Karin L Klingman; Simon Collins; H Clifford Lane; Andrew N Phillips; James D Neaton Journal: N Engl J Med Date: 2015-07-20 Impact factor: 91.245
Authors: Mark Bower; Alessia Dalla Pria; Chris Coyle; Eileen Andrews; Victoria Tittle; Sharanjit Dhoot; Mark Nelson Journal: J Clin Oncol Date: 2013-12-30 Impact factor: 44.544
Authors: Sergio Serrano-Villar; Talia Sainz; Sulggi A Lee; Peter W Hunt; Elizabeth Sinclair; Barbara L Shacklett; April L Ferre; Timothy L Hayes; Ma Somsouk; Priscilla Y Hsue; Mark L Van Natta; Curtis L Meinert; Michael M Lederman; Hiroyu Hatano; Vivek Jain; Yong Huang; Frederick M Hecht; Jeffrey N Martin; Joseph M McCune; Santiago Moreno; Steven G Deeks Journal: PLoS Pathog Date: 2014-05-15 Impact factor: 6.823
Authors: Ross D Cranston; Michelle S Cespedes; Pawel Paczuski; Ming Yang; Robert W Coombs; Joan Dragavon; Alfred Saah; Catherine Godfrey; Jennifer Y Webster-Cyriaque; Elizabeth Y Chiao; Barbara Bastow; Timothy Wilkin Journal: Sex Transm Dis Date: 2018-04 Impact factor: 2.830
Authors: Álvaro H Borges; Jacqueline Neuhaus; Shweta Sharma; James D Neaton; Keith Henry; Olga Anagnostou; Teresa Staub; Sean Emery; Jens D Lundgren Journal: J Infect Dis Date: 2019-01-07 Impact factor: 5.226
Authors: Keri N Althoff; Kelly A Gebo; Richard D Moore; Cynthia M Boyd; Amy C Justice; Cherise Wong; Gregory M Lucas; Marina B Klein; Mari M Kitahata; Heidi Crane; Michael J Silverberg; M John Gill; William Christopher Mathews; Robert Dubrow; Michael A Horberg; Charles S Rabkin; Daniel B Klein; Vincent Lo Re; Timothy R Sterling; Fidel A Desir; Kenneth Lichtenstein; James Willig; Anita R Rachlis; Gregory D Kirk; Kathryn Anastos; Frank J Palella; Jennifer E Thorne; Joseph Eron; Lisa P Jacobson; Sonia Napravnik; Chad Achenbach; Angel M Mayor; Pragna Patel; Kate Buchacz; Yuezhou Jing; Stephen J Gange Journal: Lancet HIV Date: 2019-01-22 Impact factor: 12.767
Authors: Lesley S Park; Janet P Tate; Keith Sigel; Sheldon T Brown; Kristina Crothers; Cynthia Gibert; Matthew Bidwell Goetz; David Rimland; Maria C Rodriguez-Barradas; Roger J Bedimo; Amy C Justice; Robert Dubrow Journal: Ann Intern Med Date: 2018-06-12 Impact factor: 25.391