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.

Cancer risk and use of protease inhibitor or nonnucleoside reverse transcriptase inhibitor-based combination antiretroviral therapy: The D:A:D Study / M. Bruyand, L. Ryom, L. Shepherd, G. Fatkenheuer, A. Grulich, P. Reiss, S. de Wit, A. D'Arminio Monforte, H. Furrer, C. Pradier, J. Lundgren, C. Sabin. - In: JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES. - ISSN 1525-4135. - 68:5(2015 Apr 15), pp. 568-577. [10.1097/QAI.0000000000000523]

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

A. D'Arminio Monforte;
2015

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.
antiretroviral therapy; cancer; HIV; risk
Settore MED/17 - Malattie Infettive
15-apr-2015
Article (author)
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/280177
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