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Immediate antiretroviral therapy reduces risk of infection-related cancer during early HIV infection

  1. Ronald Mitsuyasu16
  2. for the INSIGHT START Study Group
  1. 1Centre for Health & Infectious Diseases Research (CHIP), Department of Infectious Diseases, section 2100, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
  2. 2Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, Minnesota, USA
  3. 3Medical Research Council Clinical Trials Unit at University College London, University College London, London, UK
  4. 4Hennepin County Medical Center, Minneapolis, Minnesota, USA
  5. 5Division of Infectious Disease, UT Southwestern Medical Center, Dallas, Texas, USA
  6. 6Department of Infectious Diseases, University Hospitals Leicester NHS Trust , Leicester, UK
  7. 7Joint Clinical Research Center, Kampala, Uganda
  8. 8Infectious Diseases Unit, Hospital de la Santa Creu i Sant Pau, Autonomous University of Barcelona and Red de Investigación en SIDA (RIS), Barcelona, Spain
  9. 9Infektionsmedizinisches Centrum Hamburg (ICH) Study Center, Hamburg, Germany
  10. 10Department of Medicine II, University of Schleswig-Holstein, Campus Kiel, Kiel, Germany
  11. 11Melbourne Sexual Health Centre, Alfred Hospital and Central Clinical School, Monash University, Melbourne, Australia
  12. 12Institute of Infectious Diseases, Pune, Maharashtra, India
  13. 13Projecte dels Noms/Hispanosida, Barcelona, Spain
  14. 14Ian Charleson Day Centre, Royal Free Hospital, London, UK
  15. 15Division of Infectious Diseases, Weill Cornell Medicine, New York, New York, USA
  16. 16Center for Clinical AIDS Research & Education, David Geffen School of Medicine, University of California, Los Angeles, California, USA
  1. Corresponding author: Álvaro H. Borges MD MSc PhD at CHIP, Department of Infectious Diseases, section 2100, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen Ø, Denmark. Fax: +45 3545 5758. Tel: +45 3545 5785. Email: alvaro.borges{at}regionh.dk

Abstract

Background. In the START study, immediate combination antiretroviral therapy (cART) reduced cancer risk by 64%. We hypothesized that risk reduction was higher for infection-related cancer and determined by differences in CD4 counts and 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; 95% CI; of immediate vs deferred cART initiation were 0.26; 0.11-0.64; for infection-related and 0.49; 0.21-1.15; for infection-unrelated cancer). Independent predictors of infection-related cancer were older age, higher BMI, low-middle income region, HIV RNA and baseline CD8 count. Older age and baseline CD8 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 count or cancer risk factors, attenuated the effect of immediate cART on infection-unrelated cancer.

Conclusions. Immediate cART initiation significantly reduces risk of cancer. Though limited by small sample size, this benefit doesn't appear to be solely attributable to HIV RNA suppression and may be also mediated by other mechanisms.

UNCORRECTED PROOF

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