Brief Report: Protease Inhibitors Versus Nonnucleoside Reverse Transcriptase Inhibitors and the Risk of Cancer Among People With HIV

Sally B. Coburn; Noel Pimentel; Wendy Leyden; Mari M. Kitahata; Richard D. Moore; Keri N. Althoff; M. John Gill; Raynell Lang; Michael A. Horberg; Gypsy Amber D'Souza; Shehnaz K. Hussain; Robert Dubrow; Richard M. Novak; Charles S. Rabkin; Lesley S. Park; Timothy R. Sterling; Romain S. Neugebauer; Michael J. Silverberg; Constance A. Benson; Ronald J. Bosch; Gregory D. Kirk; Vincent Marconi; Jonathan Colasanti; Kenneth H. Mayer; Chris Grasso; Robert S. Hogg; Viviane D. Lima; Zabrina Brumme; Julio S.G. Montaner; Paul Sereda; Jason Trigg; Kate Salters; Kate Buchacz; Jun Li; Kelly A. Gebo; Richard D. Moore; Richard D. Moore; Jeffrey Jacobson; Michael A. Horberg; Michael J. Silverberg; Jennifer E. Thorne; Todd Brown; Phyllis Tien; Gypsyamber D'Souza; Graham Smith; Mona Loutfy; Meenakshi Gupta; Marina B. Klein; Charles Rabkin; Abigail Kroch; Ann Burchell; Adrian Betts; Joanne Lindsay; Ank Nijhawan; Angel M. Mayor; Jeffrey N. Martin; Steven G. Deeks; Jun Li; John T. Brooks; Michael S. Saag; Michael J. Mugavero; Greer Burkholder; Laura Bamford; Maile Karris; Joseph J. Eron; Sonia Napravnik; Mari M. Kitahata; Heidi M. Crane; Timothy R. Sterling; David Haas; Peter Rebeiro; Megan Turner; Lesley Park; Kathleen McGinnis; Amy Justice; Richard D. Moore; Keri N. Althoff; Stephen J. Gange; Mari M. Kitahata; Jennifer S. Lee; Michael A. Horberg; Marina B. Klein; Rosemary G. McKaig; Aimee M. Freeman; Richard D. Moore; Keri N. Althoff; Aimee M. Freeman; Mari M. Kitahata; Stephen E. Van Rompaey; Heidi M. Crane; Liz Morton; Justin McReynolds; William B. Lober; Stephen J. Gange; Jennifer S. Lee; Brenna Hogan; Elizabeth Humes; Sally B. Coburn; Lucas Gerace

doi:10.1097/QAI.0000000000003436

Brief Report: Protease Inhibitors Versus Nonnucleoside Reverse Transcriptase Inhibitors and the Risk of Cancer Among People With HIV

Sally B. Coburn, Noel Pimentel, Wendy Leyden, Mari M. Kitahata, Richard D. Moore, Keri N. Althoff, M. John Gill, Raynell Lang, Michael A. Horberg, Gypsy Amber D'Souza, Shehnaz K. Hussain, Robert Dubrow, Richard M. Novak, Charles S. Rabkin, Lesley S. Park, Timothy R. Sterling, Romain S. Neugebauer, Michael J. Silverberg, Constance A. Benson, Ronald J. BoschGregory D. Kirk, Vincent Marconi, Jonathan Colasanti, Kenneth H. Mayer, Chris Grasso, Robert S. Hogg, Viviane D. Lima, Zabrina Brumme, Julio S.G. Montaner, Paul Sereda, Jason Trigg, Kate Salters, Kate Buchacz, Jun Li, Kelly A. Gebo, Richard D. Moore, Richard D. Moore, Jeffrey Jacobson, Michael A. Horberg, Michael J. Silverberg, Jennifer E. Thorne, Todd Brown, Phyllis Tien, Gypsyamber D'Souza, Graham Smith, Mona Loutfy, Meenakshi Gupta, Marina B. Klein, Charles Rabkin, Abigail Kroch, Ann Burchell, Adrian Betts, Joanne Lindsay, Ank Nijhawan, Angel M. Mayor, Jeffrey N. Martin, Steven G. Deeks, Jun Li, John T. Brooks, Michael S. Saag, Michael J. Mugavero, Greer Burkholder, Laura Bamford, Maile Karris, Joseph J. Eron, Sonia Napravnik, Mari M. Kitahata, Heidi M. Crane, Timothy R. Sterling, David Haas, Peter Rebeiro, Megan Turner, Lesley Park, Kathleen McGinnis, Amy Justice, Richard D. Moore, Keri N. Althoff, Stephen J. Gange, Mari M. Kitahata, Jennifer S. Lee, Michael A. Horberg, Marina B. Klein, Rosemary G. McKaig, Aimee M. Freeman, Richard D. Moore, Keri N. Althoff, Aimee M. Freeman, Mari M. Kitahata, Stephen E. Van Rompaey, Heidi M. Crane, Liz Morton, Justin McReynolds, William B. Lober, Stephen J. Gange, Jennifer S. Lee, Brenna Hogan, Elizabeth Humes, Sally B. Coburn, Lucas Gerace

Bloomberg School of Public Health

Research output: Contribution to journal › Article › peer-review

Abstract

Background:The effect of initial antiretroviral therapy (ART) class on cancer risk in people with HIV (PWH) remains unclear.Setting:A cohort study of 36,322 PWH enrolled (1996-2014) in the North American AIDS Cohort Collaboration on Research and Design.Methods:We followed individuals from ART initiation (protease inhibitor [PI]-based, nonnucleoside reverse transcriptase inhibitor [NNRTI]-based, or integrase strand transfer inhibitor [INSTI]-based) until incident cancer, death, loss-to-follow-up, December 31, 2014, 85 months (intention-to-treat analyses [ITT]), or 30 months (per-protocol [PP] analyses). Cancers were grouped (nonmutually exclusive) as follows: any cancer, AIDS-defining cancers (ADC), non-AIDS-defining cancers (NADC), any infection-related cancer, and common individual cancer types. We estimated adjusted hazard ratios (aHR) comparing cancer risk by ART class using marginal structural models emulating ITT and PP trials.Results:We observed 17,004 PWH (954 cancers) with PI-based (median 6 years follow-up), 17,536 (770 cancers) with NNRTI-based (median 5 years follow-up), and 1782 (29 cancers) with INSTI-based ART (median 2 years follow-up). Analyses with 85-month follow-up indicated no cancer risk differences. In truncated analyses, the risk of ADCs (aHR 1.33; 95% CI: 1.00, 1.77 [PP analysis]) and NADCs (aHR 1.23; 95% CI: 1.00 to 1.51 [ITT analysis]) was higher comparing PIs vs. NNRTIs.Conclusions:Results with longer-term follow-up suggest being on a PI-based versus NNRTI-based ART regimen does not affect cancer risk. We observed shorter-term associations that should be interpreted cautiously and warrant further study. Further research with a longer duration of follow-up that can evaluate INSTIs, the current first-line recommended therapy, is needed to comprehensively characterize the association between ART class and cancer risk.

Original language	English (US)
Pages (from-to)	393-398
Number of pages	6
Journal	Journal of Acquired Immune Deficiency Syndromes
Volume	96
Issue number	4
DOIs	https://doi.org/10.1097/QAI.0000000000003436
State	Published - Aug 1 2024

Keywords

ART class
HIV
NNRTI
PI
cancer

ASJC Scopus subject areas

Infectious Diseases
Pharmacology (medical)

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10.1097/QAI.0000000000003436

Cite this

Coburn, S. B., Pimentel, N., Leyden, W., Kitahata, M. M., Moore, R. D., Althoff, K. N., Gill, M. J., Lang, R., Horberg, M. A., D'Souza, G. A., Hussain, S. K., Dubrow, R., Novak, R. M., Rabkin, C. S., Park, L. S., Sterling, T. R., Neugebauer, R. S., Silverberg, M. J., Benson, C. A., ... Gerace, L. (2024). Brief Report: Protease Inhibitors Versus Nonnucleoside Reverse Transcriptase Inhibitors and the Risk of Cancer Among People With HIV. Journal of Acquired Immune Deficiency Syndromes, 96(4), 393-398. https://doi.org/10.1097/QAI.0000000000003436

Coburn, SB, Pimentel, N, Leyden, W, Kitahata, MM, Moore, RD , Althoff, KN, Gill, MJ, Lang, R, Horberg, MA, D'Souza, GA, Hussain, SK, Dubrow, R, Novak, RM, Rabkin, CS, Park, LS, Sterling, TR, Neugebauer, RS, Silverberg, MJ, Benson, CA, Bosch, RJ, Kirk, GD, Marconi, V, Colasanti, J, Mayer, KH, Grasso, C, Hogg, RS, Lima, VD, Brumme, Z, Montaner, JSG, Sereda, P, Trigg, J, Salters, K, Buchacz, K, Li, J, Gebo, KA, Moore, RD, Moore, RD, Jacobson, J, Horberg, MA, Silverberg, MJ, Thorne, JE , Brown, T, Tien, P, D'Souza, G, Smith, G, Loutfy, M, Gupta, M, Klein, MB, Rabkin, C, Kroch, A, Burchell, A, Betts, A, Lindsay, J, Nijhawan, A, Mayor, AM, Martin, JN, Deeks, SG, Li, J, Brooks, JT, Saag, MS, Mugavero, MJ, Burkholder, G, Bamford, L, Karris, M, Eron, JJ, Napravnik, S, Kitahata, MM, Crane, HM, Sterling, TR, Haas, D, Rebeiro, P, Turner, M, Park, L, McGinnis, K, Justice, A, Moore, RD, Althoff, KN, Gange, SJ, Kitahata, MM, Lee, JS, Horberg, MA, Klein, MB, McKaig, RG, Freeman, AM, Moore, RD, Althoff, KN, Freeman, AM, Kitahata, MM, Van Rompaey, SE, Crane, HM, Morton, L, McReynolds, J, Lober, WB, Gange, SJ, Lee, JS, Hogan, B, Humes, E, Coburn, SB & Gerace, L 2024, 'Brief Report: Protease Inhibitors Versus Nonnucleoside Reverse Transcriptase Inhibitors and the Risk of Cancer Among People With HIV', Journal of Acquired Immune Deficiency Syndromes, vol. 96, no. 4, pp. 393-398. https://doi.org/10.1097/QAI.0000000000003436

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title = "Brief Report: Protease Inhibitors Versus Nonnucleoside Reverse Transcriptase Inhibitors and the Risk of Cancer Among People With HIV",

abstract = "Background:The effect of initial antiretroviral therapy (ART) class on cancer risk in people with HIV (PWH) remains unclear.Setting:A cohort study of 36,322 PWH enrolled (1996-2014) in the North American AIDS Cohort Collaboration on Research and Design.Methods:We followed individuals from ART initiation (protease inhibitor [PI]-based, nonnucleoside reverse transcriptase inhibitor [NNRTI]-based, or integrase strand transfer inhibitor [INSTI]-based) until incident cancer, death, loss-to-follow-up, December 31, 2014, 85 months (intention-to-treat analyses [ITT]), or 30 months (per-protocol [PP] analyses). Cancers were grouped (nonmutually exclusive) as follows: any cancer, AIDS-defining cancers (ADC), non-AIDS-defining cancers (NADC), any infection-related cancer, and common individual cancer types. We estimated adjusted hazard ratios (aHR) comparing cancer risk by ART class using marginal structural models emulating ITT and PP trials.Results:We observed 17,004 PWH (954 cancers) with PI-based (median 6 years follow-up), 17,536 (770 cancers) with NNRTI-based (median 5 years follow-up), and 1782 (29 cancers) with INSTI-based ART (median 2 years follow-up). Analyses with 85-month follow-up indicated no cancer risk differences. In truncated analyses, the risk of ADCs (aHR 1.33; 95% CI: 1.00, 1.77 [PP analysis]) and NADCs (aHR 1.23; 95% CI: 1.00 to 1.51 [ITT analysis]) was higher comparing PIs vs. NNRTIs.Conclusions:Results with longer-term follow-up suggest being on a PI-based versus NNRTI-based ART regimen does not affect cancer risk. We observed shorter-term associations that should be interpreted cautiously and warrant further study. Further research with a longer duration of follow-up that can evaluate INSTIs, the current first-line recommended therapy, is needed to comprehensively characterize the association between ART class and cancer risk.",

keywords = "ART class, HIV, NNRTI, PI, cancer",

author = "Coburn, {Sally B.} and Noel Pimentel and Wendy Leyden and Kitahata, {Mari M.} and Moore, {Richard D.} and Althoff, {Keri N.} and Gill, {M. John} and Raynell Lang and Horberg, {Michael A.} and D'Souza, {Gypsy Amber} and Hussain, {Shehnaz K.} and Robert Dubrow and Novak, {Richard M.} and Rabkin, {Charles S.} and Park, {Lesley S.} and Sterling, {Timothy R.} and Neugebauer, {Romain S.} and Silverberg, {Michael J.} and Benson, {Constance A.} and Bosch, {Ronald J.} and Kirk, {Gregory D.} and Vincent Marconi and Jonathan Colasanti and Mayer, {Kenneth H.} and Chris Grasso and Hogg, {Robert S.} and Lima, {Viviane D.} and Zabrina Brumme and Montaner, {Julio S.G.} and Paul Sereda and Jason Trigg and Kate Salters and Kate Buchacz and Jun Li and Gebo, {Kelly A.} and Moore, {Richard D.} and Moore, {Richard D.} and Jeffrey Jacobson and Horberg, {Michael A.} and Silverberg, {Michael J.} and Thorne, {Jennifer E.} and Todd Brown and Phyllis Tien and Gypsyamber D'Souza and Graham Smith and Mona Loutfy and Meenakshi Gupta and Klein, {Marina B.} and Charles Rabkin and Abigail Kroch and Ann Burchell and Adrian Betts and Joanne Lindsay and Ank Nijhawan and Mayor, {Angel M.} and Martin, {Jeffrey N.} and Deeks, {Steven G.} and Jun Li and Brooks, {John T.} and Saag, {Michael S.} and Mugavero, {Michael J.} and Greer Burkholder and Laura Bamford and Maile Karris and Eron, {Joseph J.} and Sonia Napravnik and Kitahata, {Mari M.} and Crane, {Heidi M.} and Sterling, {Timothy R.} and David Haas and Peter Rebeiro and Megan Turner and Lesley Park and Kathleen McGinnis and Amy Justice and Moore, {Richard D.} and Althoff, {Keri N.} and Gange, {Stephen J.} and Kitahata, {Mari M.} and Lee, {Jennifer S.} and Horberg, {Michael A.} and Klein, {Marina B.} and McKaig, {Rosemary G.} and Freeman, {Aimee M.} and Moore, {Richard D.} and Althoff, {Keri N.} and Freeman, {Aimee M.} and Kitahata, {Mari M.} and {Van Rompaey}, {Stephen E.} and Crane, {Heidi M.} and Liz Morton and Justin McReynolds and Lober, {William B.} and Gange, {Stephen J.} and Lee, {Jennifer S.} and Brenna Hogan and Elizabeth Humes and Coburn, {Sally B.} and Lucas Gerace",

note = "Publisher Copyright: Copyright {\textcopyright} 2024 Wolters Kluwer Health, Inc.",

year = "2024",

month = aug,

day = "1",

doi = "10.1097/QAI.0000000000003436",

language = "English (US)",

volume = "96",

pages = "393--398",

journal = "Journal of Acquired Immune Deficiency Syndromes",

issn = "1525-4135",

publisher = "Wolters Kluwer Health",

number = "4",

}

TY - JOUR

T1 - Brief Report

T2 - Protease Inhibitors Versus Nonnucleoside Reverse Transcriptase Inhibitors and the Risk of Cancer Among People With HIV

AU - Coburn, Sally B.

AU - Pimentel, Noel

AU - Leyden, Wendy

AU - Kitahata, Mari M.

AU - Moore, Richard D.

AU - Althoff, Keri N.

AU - Gill, M. John

AU - Lang, Raynell

AU - Horberg, Michael A.

AU - D'Souza, Gypsy Amber

AU - Hussain, Shehnaz K.

AU - Dubrow, Robert

AU - Novak, Richard M.

AU - Rabkin, Charles S.

AU - Park, Lesley S.

AU - Sterling, Timothy R.

AU - Neugebauer, Romain S.

AU - Silverberg, Michael J.

AU - Benson, Constance A.

AU - Bosch, Ronald J.

AU - Kirk, Gregory D.

AU - Marconi, Vincent

AU - Colasanti, Jonathan

AU - Mayer, Kenneth H.

AU - Grasso, Chris

AU - Hogg, Robert S.

AU - Lima, Viviane D.

AU - Brumme, Zabrina

AU - Montaner, Julio S.G.

AU - Sereda, Paul

AU - Trigg, Jason

AU - Salters, Kate

AU - Buchacz, Kate

AU - Li, Jun

AU - Gebo, Kelly A.

AU - Moore, Richard D.

AU - Jacobson, Jeffrey

AU - Horberg, Michael A.

AU - Silverberg, Michael J.

AU - Thorne, Jennifer E.

AU - Brown, Todd

AU - Tien, Phyllis

AU - D'Souza, Gypsyamber

AU - Smith, Graham

AU - Loutfy, Mona

AU - Gupta, Meenakshi

AU - Klein, Marina B.

AU - Rabkin, Charles

AU - Kroch, Abigail

AU - Burchell, Ann

AU - Betts, Adrian

AU - Lindsay, Joanne

AU - Nijhawan, Ank

AU - Mayor, Angel M.

AU - Martin, Jeffrey N.

AU - Deeks, Steven G.

AU - Li, Jun

AU - Brooks, John T.

AU - Saag, Michael S.

AU - Mugavero, Michael J.

AU - Burkholder, Greer

AU - Bamford, Laura

AU - Karris, Maile

AU - Eron, Joseph J.

AU - Napravnik, Sonia

AU - Kitahata, Mari M.

AU - Crane, Heidi M.

AU - Sterling, Timothy R.

AU - Haas, David

AU - Rebeiro, Peter

AU - Turner, Megan

AU - Park, Lesley

AU - McGinnis, Kathleen

AU - Justice, Amy

AU - Moore, Richard D.

AU - Althoff, Keri N.

AU - Gange, Stephen J.

AU - Kitahata, Mari M.

AU - Lee, Jennifer S.

AU - Horberg, Michael A.

AU - Klein, Marina B.

AU - McKaig, Rosemary G.

AU - Freeman, Aimee M.

AU - Moore, Richard D.

AU - Althoff, Keri N.

AU - Freeman, Aimee M.

AU - Kitahata, Mari M.

AU - Van Rompaey, Stephen E.

AU - Crane, Heidi M.

AU - Morton, Liz

AU - McReynolds, Justin

AU - Lober, William B.

AU - Gange, Stephen J.

AU - Lee, Jennifer S.

AU - Hogan, Brenna

AU - Humes, Elizabeth

AU - Coburn, Sally B.

AU - Gerace, Lucas

PY - 2024/8/1

Y1 - 2024/8/1

N2 - Background:The effect of initial antiretroviral therapy (ART) class on cancer risk in people with HIV (PWH) remains unclear.Setting:A cohort study of 36,322 PWH enrolled (1996-2014) in the North American AIDS Cohort Collaboration on Research and Design.Methods:We followed individuals from ART initiation (protease inhibitor [PI]-based, nonnucleoside reverse transcriptase inhibitor [NNRTI]-based, or integrase strand transfer inhibitor [INSTI]-based) until incident cancer, death, loss-to-follow-up, December 31, 2014, 85 months (intention-to-treat analyses [ITT]), or 30 months (per-protocol [PP] analyses). Cancers were grouped (nonmutually exclusive) as follows: any cancer, AIDS-defining cancers (ADC), non-AIDS-defining cancers (NADC), any infection-related cancer, and common individual cancer types. We estimated adjusted hazard ratios (aHR) comparing cancer risk by ART class using marginal structural models emulating ITT and PP trials.Results:We observed 17,004 PWH (954 cancers) with PI-based (median 6 years follow-up), 17,536 (770 cancers) with NNRTI-based (median 5 years follow-up), and 1782 (29 cancers) with INSTI-based ART (median 2 years follow-up). Analyses with 85-month follow-up indicated no cancer risk differences. In truncated analyses, the risk of ADCs (aHR 1.33; 95% CI: 1.00, 1.77 [PP analysis]) and NADCs (aHR 1.23; 95% CI: 1.00 to 1.51 [ITT analysis]) was higher comparing PIs vs. NNRTIs.Conclusions:Results with longer-term follow-up suggest being on a PI-based versus NNRTI-based ART regimen does not affect cancer risk. We observed shorter-term associations that should be interpreted cautiously and warrant further study. Further research with a longer duration of follow-up that can evaluate INSTIs, the current first-line recommended therapy, is needed to comprehensively characterize the association between ART class and cancer risk.

AB - Background:The effect of initial antiretroviral therapy (ART) class on cancer risk in people with HIV (PWH) remains unclear.Setting:A cohort study of 36,322 PWH enrolled (1996-2014) in the North American AIDS Cohort Collaboration on Research and Design.Methods:We followed individuals from ART initiation (protease inhibitor [PI]-based, nonnucleoside reverse transcriptase inhibitor [NNRTI]-based, or integrase strand transfer inhibitor [INSTI]-based) until incident cancer, death, loss-to-follow-up, December 31, 2014, 85 months (intention-to-treat analyses [ITT]), or 30 months (per-protocol [PP] analyses). Cancers were grouped (nonmutually exclusive) as follows: any cancer, AIDS-defining cancers (ADC), non-AIDS-defining cancers (NADC), any infection-related cancer, and common individual cancer types. We estimated adjusted hazard ratios (aHR) comparing cancer risk by ART class using marginal structural models emulating ITT and PP trials.Results:We observed 17,004 PWH (954 cancers) with PI-based (median 6 years follow-up), 17,536 (770 cancers) with NNRTI-based (median 5 years follow-up), and 1782 (29 cancers) with INSTI-based ART (median 2 years follow-up). Analyses with 85-month follow-up indicated no cancer risk differences. In truncated analyses, the risk of ADCs (aHR 1.33; 95% CI: 1.00, 1.77 [PP analysis]) and NADCs (aHR 1.23; 95% CI: 1.00 to 1.51 [ITT analysis]) was higher comparing PIs vs. NNRTIs.Conclusions:Results with longer-term follow-up suggest being on a PI-based versus NNRTI-based ART regimen does not affect cancer risk. We observed shorter-term associations that should be interpreted cautiously and warrant further study. Further research with a longer duration of follow-up that can evaluate INSTIs, the current first-line recommended therapy, is needed to comprehensively characterize the association between ART class and cancer risk.

KW - ART class

KW - HIV

KW - NNRTI

KW - PI

KW - cancer

UR - http://www.scopus.com/inward/record.url?scp=85198138233&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85198138233&partnerID=8YFLogxK

U2 - 10.1097/QAI.0000000000003436

DO - 10.1097/QAI.0000000000003436

M3 - Article

C2 - 39720558

AN - SCOPUS:85198138233

SN - 1525-4135

VL - 96

SP - 393

EP - 398

JO - Journal of Acquired Immune Deficiency Syndromes

JF - Journal of Acquired Immune Deficiency Syndromes

IS - 4

ER -

Brief Report: Protease Inhibitors Versus Nonnucleoside Reverse Transcriptase Inhibitors and the Risk of Cancer Among People With HIV

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