Integrase Strand Transfer Inhibitor Use and Cancer Incidence in a Large Cohort Setting

Lauren Greenberg; Lene Ryom; Bastian Neesgaard; Jose M Miró; Line Dahlerup Rasmussen; Robert Zangerle; Katharina Grabmeier-Pfistershammer; Huldrych F Günthard; Katharina Kusejko; Colette Smith; Cristina Mussini; Marianna Menozzi; Ferdinand Wit; Marc Van Der Valk; Antonella d'Arminio Monforte; Stéphane De Wit; Coca Necsoi; Annegret Pelchen-Matthews; Jens Lundgren; Lars Peters; Antonella Castagna; Camilla Muccini; Jörg Janne Vehreschild; Christian Pradier; Andreu Bruguera Riera; Anders Sönnerborg; Kathy Petoumenos; Harmony Garges; Felipe Rogatto; Nikos Dedes; Loveleen Bansi-Matharu; Amanda Mocroft; RESPOND Study Group

doi:10.1093/ofid/ofac029

Integrase Strand Transfer Inhibitor Use and Cancer Incidence in a Large Cohort Setting

Open Forum Infect Dis. 2022 Jan 19;9(3):ofac029. doi: 10.1093/ofid/ofac029. eCollection 2022 Mar.

Authors

Lauren Greenberg¹, Lene Ryom², Bastian Neesgaard², Jose M Miró³, Line Dahlerup Rasmussen⁴, Robert Zangerle⁵, Katharina Grabmeier-Pfistershammer⁶, Huldrych F Günthard^{7

8}, Katharina Kusejko^{7

8}, Colette Smith¹, Cristina Mussini⁹, Marianna Menozzi¹⁰, Ferdinand Wit¹¹, Marc Van Der Valk^{11

12}, Antonella d'Arminio Monforte¹³, Stéphane De Wit¹⁴, Coca Necsoi¹⁵, Annegret Pelchen-Matthews¹, Jens Lundgren², Lars Peters², Antonella Castagna¹⁶, Camilla Muccini¹⁶, Jörg Janne Vehreschild^{17

18}, Christian Pradier¹⁹, Andreu Bruguera Riera²⁰, Anders Sönnerborg²¹, Kathy Petoumenos²², Harmony Garges²³, Felipe Rogatto²⁴, Nikos Dedes²⁵, Loveleen Bansi-Matharu¹, Amanda Mocroft^{1

2}; RESPOND Study Group

Collaborators

RESPOND Study Group:
F Wit, P Reiss, M Law, K Petoumenos, N Rose, R Zangerle, H Appoyer, S De Wit, M Delforge, G Wandeler, C Stephan, M Bucht, N Chkhartishvili, O Chokoshvili, A d'Arminio Monforte, A Rodano, A Tavelli, C Mussini, V Borghi, C Pradier, E Fontas, K Dollet, C Caissotti, J Casabona, J M Miro, J M Llibre, A Riera, J Reyes-Urueña, C Smith, F Lampe, A Castagna, A Lazzarin, A Poli, A Sönnerborg, K Falconer, V Svedhem, H Günthard, B Ledergerber, H Bucher, K Kusejko, J C Wasmuth, J Rockstroh, J J Vehreschild, G Fätkenheuer, A Mocroft, J Rooney, F Rogatto, V Vannappagari, H Garges, G Wandeler, M Law, R Zangerle, C Smith, S De Wit, J Lundgren, H Günthard, J Lundgren, H Günthard, J Kowalska, D Raben, L Ryom, A Mocroft, J Rockstroh, L Peters, A Volny Anne, N Dedes, E D Williams, N Chkhartishvili, R Zangerle, M Law, F Wit, C Necsoi, G Wandeler, C Stephan, C Pradier, A D'Arminio Monforte, C Mussini, A Bruguera, H Bucher, A Sönnerborg, J J Vehreschild, J C Wasmuth, C Smith, A Castagna, F Rogatto, R Haubrich, V Vannappagari, H Garges, L Ryom, A Mocroft, B Neesgaard, L Greenberg, L Bansi-Matharu, V Svedhem-Johansson, F Wit, K Grabmeier-Pfistershammer, R Zangerle, J Hoy, M Bloch, D Braun, A Calmy, G Schüttfort, M Youle, S De Wit, C Mussini, S Zona, A Castagna, A Antinori, N Chkhartishvili, N Bolokadze, E Fontas, K Dollet, C Pradier, J M Miro, J M Llibre, J J Vehreschild, C Schwarze-Zander, J C Wasmuth, J Rockstroh, K Petoumenos, M Law, C Duvivier, G Dragovic, R Radoi, C Oprea, M Vasylyev, J Kowalska, R Matulionyte, V Mulabdic, G Marchetti, E Kuzovatova, N Coppola, J Begovac, I Aho, S Martini, H Bucher, A Harxhi, T Wæhre, A Pharris, A Vassilenko, G Fätkenheuer, J Bogner, A Maagaard, E Jablonowska, D Elbirt, G Marrone, C Leen, C Wyen, M Kundro, N Dedes, E Dixon Williams, J Gallant, D Thorpe, H Diaz Cuervo, V Vannappagari, H Garges, A Volny-Anne, N Dedes, L Mendao, E Dixon Williams, D Raben, L Peters, L Ryom, B Neesgaard, J F Larsen, M L Jakobsen, T Bruun, A Bojesen, E V Hansen, T W Elsing, D Kristensen, S Thomsen, T Weide, A Mocroft, L Greenberg, A Mocroft, L Greenberg, L Bansi-Matharu, A Pelchen-Matthews, K Petoumenos, N Rose, D Byonanebye

Affiliations

¹ Centre for Clinical Research, Epidemiology, Modelling and Evaluation, Institute for Global Health, University College London, London, United Kingdom.
² CHIP, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
³ Hospital Clinic-IDIBAPS, University of Barcelona, Barcelona, Spain.
⁴ Department of Infectious Diseases, Odense University Hospital, Odense, Denmark.
⁵ Austrian HIV Cohort Study (AHIVCOS), Medizinische Universität Innsbruck, Innsbruch, Austria.
⁶ Medical University Vienna, Vienna, Austria.
⁷ Department of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland.
⁸ Institute of Medical Virology, University of Zurich, Zurich, Switzerland.
⁹ Modena HIV Cohort, Università degli Studi di Modena, Modena, Italy.
¹⁰ Azienda Ospedaliero Universitaria di Modena, Modena, Italy.
¹¹ AIDS Therapy Evaluation in the Netherlands Cohort (ATHENA), HIV Monitoring Foundation, Amsterdam, the Netherlands.
¹² Department of Infectious Diseases, Amsterdam Infection and Immunity Institute, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
¹³ Italian Cohort Naive Antiretrovirals (ICoNA), ASST Santi Paolo e Carlo, Milano, Italy.
¹⁴ CHU Saint-Pierre, Infectious Diseases, Saint-PIerre University Hospital, Université Libre de Bruxelles, Brussels, Belgium.
¹⁵ CHU Saint-Pierre, Centre de Recherche en Maladies Infectieuses a.s.b.l., Brussels, Belgium.
¹⁶ San Raffaele Scientific Institute, Università Vita-Salute San Raffaele, Milano, Italy.
¹⁷ Medical Department 2, Hematology/Oncology, University Hospital of Frankfurt, Frankfurt, Germany.
¹⁸ Department I for Internal Medicine, University Hospital of Cologne, Cologne, Germany.
¹⁹ Nice HIV Cohort, Université Côte d'Azur et Centre Hospitalier Universitaire, Nice, France.
²⁰ PISCIS Cohort Study, Centre Estudis Epidemiologics de ITS i VIH de Catalunya, Badalona, Spain.
²¹ Swedish InfCare HIV Cohort, Karolinska University Hospital, Stockholm, Sweden.
²² The Australian HIV Observational Database (AHOD), UNSW, Sydney, Australia.
²³ ViiV Healthcare, Research Triangle Park, North Carolina, USA.
²⁴ Gilead Science, Foster City, California, USA.
²⁵ European AIDS Treatment Group, Brussels, Belgium.

Abstract

Background: Limited data exist examining the association between incident cancer and cumulative integrase inhibitor (INSTI) exposure.

Methods: Participants were followed from baseline (latest of local cohort enrollment or January 1, 2012) until the earliest of first cancer, final follow-up, or December 31, 2019. Negative binomial regression was used to assess associations between cancer incidence and time-updated cumulative INSTI exposure, lagged by 6 months.

Results: Of 29 340 individuals, 74% were male, 24% were antiretroviral treatment (ART)-naive, and median baseline age was 44 years (interquartile range [IQR], 36-51). Overall, 13 950 (48%) individuals started an INSTI during follow-up. During 160 657 person-years of follow-up ([PYFU] median 6.2; IQR, 3.9-7.5), there were 1078 cancers (incidence rate [IR] 6.7/1000 PYFU; 95% confidence interval [CI], 6.3-7.1). The commonest cancers were non-Hodgkin lymphoma (n = 113), lung cancer (112), Kaposi's sarcoma (106), and anal cancer (103). After adjusting for potential confounders, there was no association between cancer risk and INSTI exposure (≤6 months vs no exposure IR ratio: 1.15 [95% CI, 0.89-1.49], >6-12 months; 0.97 [95% CI, 0.71-1.32], >12-24 months; 0.84 [95% CI, 0.64-1.11], >24-36 months; 1.10 [95% CI, 0.82-1.47], >36 months; 0.90 [95% CI, 0.65-1.26] [P = .60]). In ART-naive participants, cancer incidence decreased with increasing INSTI exposure, mainly driven by a decreasing incidence of acquired immune deficiency syndrome cancers; however, there was no association between INSTI exposure and cancer for those ART-experienced (interaction P < .0001).

Conclusions: Cancer incidence in each INSTI exposure group was similar, despite relatively wide CIs, providing reassuring early findings that increasing INSTI exposure is unlikely to be associated with an increased cancer risk, although longer follow-up is needed to confirm this finding.

Keywords: HIV; antiretroviral treatment; cancer; cohort; integrase inhibitors.