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Cancer risk and use of protease inhibitor or nonnucleoside reverse transcriptase inhibitor-based combination antiretroviral therapy: the D: A: D study

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  • Mathias Bruyand
  • Lene Ryom Nielsen
  • Leah Shepherd
  • Gerd Fatkenheuer
  • Andrew Grulich
  • Peter Reiss
  • Stéphane de Wit
  • Antonella D Arminio Monforte
  • Hansjakob Furrer
  • Christian Pradier
  • Jens Lundgren
  • Caroline Sabin
  • D:A:D study group (Thomas Benfield, members)
  • Thomas Benfield (Member of study group)
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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.

Original languageEnglish
JournalJournal of acquired immune deficiency syndromes (1999)
Issue number5
Pages (from-to)568-77
Number of pages10
Publication statusPublished - 15 Apr 2015

    Research areas

  • Adult, Antiretroviral Therapy, Highly Active, Female, Follow-Up Studies, HIV Infections, Humans, Incidence, Male, Middle Aged, Neoplasms, Prospective Studies, Protease Inhibitors, Reverse Transcriptase Inhibitors, Risk Assessment

ID: 45586236