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

Department of Clinical Medicine

29 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.

Original language	English
Journal	Journal of acquired immune deficiency syndromes (1999)
Volume	68
Issue number	5
Pages (from-to)	568-77
Number of pages	10
ISSN	1525-4135
DOIs	https://doi.org/10.1097/QAI.0000000000000523
Publication status	Published - 15 Apr 2015

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1097/QAI.0000000000000523

Cite this

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.

In: Journal of acquired immune deficiency syndromes (1999), Vol. 68, No. 5, 15.04.2015, p. 568-77.

Research output: Contribution to journal › Journal article › Research › 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), vol. 68, no. 5, pp. 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

Abstract

Keywords

UN SDGs

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