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, Nina Friis-Møller

Research output: Contribution to journalJournal articleResearchpeer-review

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.

Original languageEnglish
JournalJ A I D S
Volume68
Issue number5
Pages (from-to)568-77
Number of pages10
ISSN1525-4135
DOIs
Publication statusPublished - 15. Apr 2015

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Reverse Transcriptase Inhibitors
Protease Inhibitors
Neoplasms
Acquired Immunodeficiency Syndrome
Kaposi's Sarcoma
Incidence
Head and Neck Neoplasms
Hodgkin Disease
Non-Hodgkin's Lymphoma

Cite this

Bruyand, Mathias ; Ryom, Lene ; Shepherd, Leah ; Fatkenheuer, Gerd ; Grulich, Andrew ; Reiss, Peter ; de Wit, Stéphane ; D Arminio Monforte, Antonella ; Furrer, Hansjakob ; Pradier, Christian ; Lundgren, Jens ; Sabin, Caroline ; D:A:D Study Group ; Friis-Møller, Nina. / Cancer risk and use of protease inhibitor or nonnucleoside reverse transcriptase inhibitor-based combination antiretroviral therapy : the D: A: D study. In: J A I D S. 2015 ; Vol. 68, No. 5. pp. 568-77.
@article{99abd96b1af948529e1ccd76d6a6b58c,
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.",
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} and Nina Friis-M{\o}ller",
year = "2015",
month = "4",
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",

}

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 & Friis-Møller, N 2015, 'Cancer risk and use of protease inhibitor or nonnucleoside reverse transcriptase inhibitor-based combination antiretroviral therapy: the D: A: D study', J A I D S, vol. 68, no. 5, pp. 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; Fatkenheuer, Gerd; Grulich, Andrew; Reiss, Peter; de Wit, Stéphane; D Arminio Monforte, Antonella; Furrer, Hansjakob; Pradier, Christian; Lundgren, Jens; Sabin, Caroline; D:A:D Study Group; Friis-Møller, Nina.

In: J A I D S, Vol. 68, No. 5, 15.04.2015, p. 568-77.

Research output: Contribution to journalJournal articleResearchpeer-review

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

AU - Friis-Møller, Nina

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.

U2 - 10.1097/QAI.0000000000000523

DO - 10.1097/QAI.0000000000000523

M3 - Journal article

VL - 68

SP - 568

EP - 577

JO - J A I D S

JF - J A I D S

SN - 1525-4135

IS - 5

ER -