Integrase Strand Transfer Inhibitor Use and Cancer Incidence in a Large Cohort Setting
Author:
Greenberg Lauren1, Ryom Lene2, Neesgaard Bastian2, Miró Jose M3, Dahlerup Rasmussen Line4, Zangerle Robert5, Grabmeier-Pfistershammer Katharina6, Günthard Huldrych F78, Kusejko Katharina78, Smith Colette1, Mussini Cristina9, Menozzi Marianna10, Wit Ferdinand11, Van Der Valk Marc1112, d’Arminio Monforte Antonella13, De Wit Stéphane14, Necsoi Coca15, Pelchen-Matthews Annegret1, Lundgren Jens2ORCID, Peters Lars2, Castagna Antonella16, Muccini Camilla16ORCID, Vehreschild Jörg Janne1718, Pradier Christian19, Bruguera Riera Andreu20, Sönnerborg Anders21, Petoumenos Kathy22, Garges Harmony23, Rogatto Felipe24, Dedes Nikos25, Bansi-Matharu Loveleen1, Mocroft Amanda12, Wit F, Reiss P, Law M, Petoumenos K, Rose N, Zangerle R, Appoyer H, De Wit S, Delforge M, Wandeler G, Stephan C, Bucht M, Chkhartishvili N, Chokoshvili O, d’Arminio Monforte A, Rodano A, Tavelli A, Mussini C, Borghi V, Pradier C, Fontas E, Dollet K, Caissotti C, Casabona J, Miro J M, Llibre J M, Riera A, Reyes-Urueña J, Smith C, Lampe F, Castagna A, Lazzarin A, Poli A, Sönnerborg A, Falconer K, Svedhem V, Günthard H, Ledergerber B, Bucher H, Kusejko K, Wasmuth J C, Rockstroh J, Vehreschild J J, Fätkenheuer G, Mocroft A, Rooney J, Rogatto F, Vannappagari V, Garges H, Wandeler G, Law M, Zangerle R, Smith C, De Wit S, Lundgren J, Günthard H, Lundgren J, Günthard H, Kowalska J, Raben D, Ryom L, Mocroft A, Rockstroh J, Peters L, Volny Anne A, Dedes N, Williams E D, Chkhartishvili N, Zangerle R, Law M, Wit F, Necsoi C, Wandeler G, Stephan C, Pradier C, D’Arminio Monforte A, Mussini C, Bruguera A, Bucher H, Sönnerborg A, Vehreschild J J, Wasmuth J C, Smith C, Castagna A, Rogatto F, Haubrich R, Vannappagari V, Garges H, Ryom L, Mocroft A, Neesgaard B, Greenberg L, Bansi-Matharu L, Svedhem-Johansson V, Wit F, Grabmeier-Pfistershammer K, Zangerle R, Hoy J, Bloch M, Braun D, Calmy A, Schüttfort G, Youle M, De Wit S, Mussini C, Zona S, Castagna A, Antinori A, Chkhartishvili N, Bolokadze N, Fontas E, Dollet K, Pradier C, Miro J M, Llibre J M, Vehreschild J J, Schwarze-Zander C, Wasmuth J C, Rockstroh J, Petoumenos K, Law M, Duvivier C, Dragovic G, Radoi R, Oprea C, Vasylyev M, Kowalska J, Matulionyte R, Mulabdic V, Marchetti G, Kuzovatova E, Coppola N, Begovac J, Aho I, Martini S, Bucher H, Harxhi A, Wæhre T, Pharris A, Vassilenko A, Fätkenheuer G, Bogner J, Maagaard A, Jablonowska E, Elbirt D, Marrone G, Leen C, Wyen C, Kundro M, Dedes N, Dixon Williams E, Gallant J, Thorpe D, Diaz Cuervo H, Vannappagari V, Garges H, Volny-Anne A, Dedes N, Mendao L, Dixon Williams E, Raben D, Peters L, Ryom L, Neesgaard B, Larsen J F, Jakobsen M L, Bruun T, Bojesen A, Hansen E V, Elsing T W, Kristensen D, Thomsen S, Weide T, Mocroft A, Greenberg L, Mocroft A, Greenberg L, Bansi-Matharu L, Pelchen-Matthews A, Petoumenos K, Rose N, Byonanebye D,
Affiliation:
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
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.
Funder
ViiV Healthcare LLC Gilead Sciences Austrian HIV Cohort Study The Australian HIV Observational Database CHU Saint-Pierre University Hospital Cologne The EuroSIDA cohort Frankfurt HIV Cohort Study Georgian National AIDS Health Information System Modena HIV Cohort San Raffaele Scientific Institute Swiss HIV Cohort Study AIDS Therapy Evaluation in the Netherlands Cohort Royal Free HIV Cohort Study
Publisher
Oxford University Press (OUP)
Subject
Infectious Diseases,Oncology
Cited by
3 articles.
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