title: Cancer risk and use of protease inhibitor or nonnucleoside reverse transcriptase inhibitor-based combination antiretroviral therapy: the D: A: D study.
abstract: BACKGROUND
  The association between combination antiretroviral therapy (cART) and cancer risk, especially regimens containing protease inhibitors (PIs) or nonnucleoside reverse transcriptase inhibitors (NNRTIs), is unclear.
  
  
  METHODS
  Participants were followed from the latest of D:A:D study entry or January 1, 2004, until the earliest of a first cancer diagnosis, February 1, 2012, death, or 6 months after the last visit. Multivariable Poisson regression models assessed associations between cumulative (per year) use of either any cART or PI/NNRTI, and the incidence of any cancer, non-AIDS-defining cancers (NADC), AIDS-defining cancers (ADC), and the most frequently occurring ADC (Kaposi sarcoma, non-Hodgkin lymphoma) and NADC (lung, invasive anal, head/neck cancers, and Hodgkin lymphoma).
  
  
  RESULTS
  A total of 41,762 persons contributed 241,556 person-years (PY). A total of 1832 cancers were diagnosed [incidence rate: 0.76/100 PY (95% confidence interval: 0.72 to 0.79)], 718 ADC [0.30/100 PY (0.28-0.32)], and 1114 NADC [0.46/100 PY (0.43-0.49)]. Longer exposure to cART was associated with a lower ADC risk [adjusted rate ratio: 0.88/year (0.85-0.92)] but a higher NADC risk [1.02/year (1.00-1.03)]. Both PI and NNRTI use were associated with a lower ADC risk [PI: 0.96/year (0.92-1.00); NNRTI: 0.86/year (0.81-0.91)]. PI use was associated with a higher NADC risk [1.03/year (1.01-1.05)]. Although this was largely driven by an association with anal cancer [1.08/year (1.04-1.13)], the association remained after excluding anal cancers from the end point [1.02/year (1.01-1.04)]. No association was seen between NNRTI use and NADC [1.00/year (0.98-1.02)].
  
  
  CONCLUSIONS
  Cumulative use of PIs may be associated with a higher risk of anal cancer and possibly other NADC. Further investigation of biological mechanisms is warranted.
authors.affiliation: *INSERM, ISPED, Centre Inserm U897-Epidemiologie-Biostatistique, Bordeaux, France; †Copenhagen HIV Programme, Department of Infectious Diseases and Rheumatology, Section 8632, Finsencenteret, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark; ‡Research Department of Infection and Population Health, UCL, London, United Kingdom; §First Department of Internal Medicine, University Hospital of Cologne, Köln, Germany; ‖German Center for Infection research (DZIF); ¶HIV Epidemiology and Prevention Program, Kirby Institute, UNSW Australia, Sydney, Australia; #Division of Infectious Diseases and Department of Global Health, Amsterdam Institute for Global Health and Development, Academic Medical Center, Amsterdam, the Netherlands; **Stichting HIV Monitoring, Amsterdam, the Netherlands; ††Department of Infectious Diseases, St Pierre University Hospital, Brussels, Belgium; ‡‡Infectious Diseases Unit, Department of Health Sciences, San Paolo University Hospital, Milan, Italy; §§Department of Infectious Diseases, Bern University Hospital and University of Bern, Bern, Switzerland; and ‖‖Département de Santé Publique, Hôpital de l'Archet, CHU de Nice, Nice, France.
authors.forename: Mathias
authors.initials: M
authors.lastname: Bruyand
authors.forename: Lene
authors.initials: L
authors.lastname: Ryom
authors.forename: Leah
authors.initials: L
authors.lastname: Shepherd
authors.forename: Gerd
authors.initials: G
authors.lastname: Fatkenheuer
authors.forename: Andrew
authors.initials: A
authors.lastname: Grulich
authors.forename: Peter
authors.initials: P
authors.lastname: Reiss
authors.forename: Stéphane
authors.initials: S
authors.lastname: de Wit
authors.forename: Antonella
authors.initials: A
authors.lastname: D Arminio Monforte
authors.forename: Hansjakob
authors.initials: H
authors.lastname: Furrer
authors.forename: Christian
authors.initials: C
authors.lastname: Pradier
authors.forename: Jens
authors.initials: J
authors.lastname: Lundgren
authors.forename: Caroline
authors.initials: C
authors.lastname: Sabin
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects* / Q000379:methods; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000453:epidemiology*; D011446:Prospective Studies; D011480:Protease Inhibitors / Q000009:adverse effects*; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects*; D018570:Risk Assessment
chemical_list: D011480:Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors