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

Mathias Bruyand; Lene Ryom; 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

doi: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

Mathias Bruyand, Lene Ryom, 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

Institut for Klinisk Medicin

29 Citationer (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.

Originalsprog	Engelsk
Tidsskrift	Journal of acquired immune deficiency syndromes (1999)
Vol/bind	68
Udgave nummer	5
Sider (fra-til)	568-77
Antal sider	10
ISSN	1525-4135
DOI	https://doi.org/10.1097/QAI.0000000000000523
Status	Udgivet - 15 apr. 2015

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10.1097/QAI.0000000000000523

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Bruyand, M., Ryom, L., Shepherd, L., Fatkenheuer, G., Grulich, A., Reiss, P., de Wit, S., D Arminio Monforte, A., Furrer, H., Pradier, C., Lundgren, J., Sabin, C., & D:A:D Study Group (2015). 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 (1999), 68(5), 568-77. https://doi.org/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. / Bruyand, Mathias; Ryom, Lene; Shepherd, Leah et al.

I: Journal of acquired immune deficiency syndromes (1999), Bind 68, Nr. 5, 15.04.2015, s. 568-77.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

Bruyand, M, Ryom, L, Shepherd, L, Fatkenheuer, G, Grulich, A, Reiss, P, de Wit, S, D Arminio Monforte, A, Furrer, H, Pradier, C, Lundgren, J, Sabin, C & D:A:D Study Group 2015, '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 (1999), bind 68, nr. 5, s. 568-77. https://doi.org/10.1097/QAI.0000000000000523

@article{c19dd49f455d457eb5930c8dc1be5a00,

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.",

keywords = "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",

author = "Mathias Bruyand and Lene Ryom and Leah Shepherd and Gerd Fatkenheuer and Andrew Grulich and Peter Reiss and {de Wit}, St{\'e}phane and {D Arminio Monforte}, Antonella and Hansjakob Furrer and Christian Pradier and Jens Lundgren and Caroline Sabin and {D:A:D Study Group}",

year = "2015",

month = apr,

day = "15",

doi = "10.1097/QAI.0000000000000523",

language = "English",

volume = "68",

pages = "568--77",

journal = "J A I D S",

issn = "1525-4135",

publisher = "Lippincott Williams & Wilkins",

number = "5",

}

TY - JOUR

T1 - Cancer risk and use of protease inhibitor or nonnucleoside reverse transcriptase inhibitor-based combination antiretroviral therapy

T2 - the D: A: D study

AU - Bruyand, Mathias

AU - Ryom, Lene

AU - Shepherd, Leah

AU - Fatkenheuer, Gerd

AU - Grulich, Andrew

AU - Reiss, Peter

AU - de Wit, Stéphane

AU - D Arminio Monforte, Antonella

AU - Furrer, Hansjakob

AU - Pradier, Christian

AU - Lundgren, Jens

AU - Sabin, Caroline

AU - D:A:D Study Group

PY - 2015/4/15

Y1 - 2015/4/15

N2 - 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.

AB - 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.

KW - Adult

KW - Antiretroviral Therapy, Highly Active

KW - Female

KW - Follow-Up Studies

KW - HIV Infections

KW - Humans

KW - Incidence

KW - Male

KW - Middle Aged

KW - Neoplasms

KW - Prospective Studies

KW - Protease Inhibitors

KW - Reverse Transcriptase Inhibitors

KW - Risk Assessment

U2 - 10.1097/QAI.0000000000000523

DO - 10.1097/QAI.0000000000000523

M3 - Journal article

C2 - 25763785

SN - 1525-4135

VL - 68

SP - 568

EP - 577

JO - J A I D S

JF - J A I D S

IS - 5

ER -

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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