Integrase Strand Transfer Inhibitor Use and Cancer Incidence in a Large Cohort Setting
Authors: Greenberg Lauren , Ryom Lene , Neesgaard Bastian , Miró Jose M , Dahlerup Rasmussen Line , Zangerle Robert , Grabmeier-Pfistershammer Katharina , Günthard Huldrych F , Kusejko Katharina , Smith Colette , Mussini Cristina , Menozzi Marianna , Wit Ferdinand , Van Der Valk Marc , d’Arminio Monforte Antonella , De Wit Stéphane , Necsoi Coca , Pelchen-Matthews Annegret , Lundgren Jens , Peters Lars , Castagna Antonella , Muccini Camilla , Vehreschild Jörg Janne , Pradier Christian , Bruguera Riera Andreu , Sönnerborg Anders , Petoumenos Kathy , Garges Harmony , Rogatto Felipe , Dedes Nikos , Bansi-Matharu Loveleen , Mocroft Amanda ,   RESPOND Study Group, 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 
Published: January 2022

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], &gt;6–12 months; 0.97 [95% CI, 0.71–1.32], &gt;12–24 months; 0.84 [95% CI, 0.64–1.11], &gt;24–36 months; 1.10 [95% CI, 0.82–1.47], &gt;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 &lt; .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.