Cancer risk and use of protease inhibitor or nonnucleoside reverse transcriptase inhibitor-based combination antiretroviral therapy: The D:A:D study: Journal of Acquired Immune Deficiency Syndromes

M. Bruyand, L. Ryom, L. Shepherd, G. Fatkenheuer, A. Grulich, P. Reiss, S. De Wit, A. Darminio Monforte, H. Furrer, C. Pradier, J. Lundgren, C. Sabin, Ferran Torres

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33 Citations (Scopus)

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. © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Original languageEnglish
Pages (from-to)568-577
Number of pages10
JournalJournal of acquired immune deficiency syndromes (1999)
Volume68
Issue number5
DOIs
Publication statusPublished - Apr 2015

Keywords

  • antiretroviral therapy
  • cancer
  • HIV
  • risk
  • nonnucleoside reverse transcriptase inhibitor
  • proteinase inhibitor
  • RNA directed DNA polymerase inhibitor
  • adult
  • anus cancer
  • Article
  • cancer diagnosis
  • cancer incidence
  • cancer mortality
  • cancer risk
  • female
  • head and neck cancer
  • highly active antiretroviral therapy
  • Hodgkin disease
  • human
  • human cell
  • invasive anal cancer
  • Kaposi sarcoma
  • lung cancer
  • major clinical study
  • male
  • nonhodgkin lymphoma
  • priority journal
  • prospective study
  • adverse effects
  • follow up
  • HIV Infections
  • incidence
  • middle aged
  • Neoplasms
  • procedures
  • risk assessment
  • Adult
  • Antiretroviral Therapy, Highly Active
  • Female
  • Follow-Up Studies
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Prospective Studies
  • Protease Inhibitors
  • Reverse Transcriptase Inhibitors
  • Risk Assessment

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