title: Association between Time on Protease Inhibitors and the Incidence of Squamous Cell Carcinoma of the Anus among U.S. Male Veterans.
abstract: Protease inhibitors (PIs) have been shown to have anti-tumor activity in addition to their antiretroviral properties. We sought to assess the association between PI use and the incidence of squamous cell carcinoma of the anus (SCCA) in HIV-infected individuals. We performed a retrospective cohort study among male US veterans diagnosed with HIV who were diagnosed between 1985 and 2010, using the Veterans Affairs HIV Clinical Case Registry (CCR). We calculated hazards ratios associated with PI use (both as percent time on PI and as 12-month intervals of PI use), utilizing time-dependent Cox models. We adjusted for risk factors, including age, race, year of enrolment into CCR, recent and nadir CD4, and percent time undetectable HIV viral load. A total of 28, 886 HIV-infected men met inclusion criteria. Of these, 373 were newly diagnosed with SCCA during the study period. In multivariate analysis, increasing percent time on PIs was associated with an increased risk of SCCA (aHR 1.07; 95% CI = 1.03-1.10 per 10% increase in time on PI). Poor immunologic recovery and virologic control, a history of condylomata acuminata, and CCR enrolment in the late combined antiretroviral therapy era were also associated with increased SCCA risk. Increasing percent time on a PI-based combined antiretroviral therapy regimen may be associated with an increased risk of developing SCCA in HIV-infected male US veterans. Future studies, better accounting for HIV control and treatment compliance, are necessary to further clarify this association.
authors.affiliation: Department of Medicine, Baylor College of Medicine, Houston, TX, United States of America.
authors.forename: Pamela A
authors.initials: PA
authors.lastname: Mbang
authors.affiliation: Department of Medicine, Baylor College of Medicine, Houston, TX, United States of America.|Houston Health Services Research and Development Center for Innovations in Quality, Effectiveness and Safety, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX, United States of America.
authors.forename: Marc A
authors.initials: MA
authors.lastname: Kowalkowski
authors.affiliation: Department of Pediatrics, Baylor College of Medicine, Houston, TX, United States of America.|Dan L Duncan Cancer Center, Baylor College of Medicine, Houston, TX, United States of America.
authors.forename: E Susan
authors.initials: ES
authors.lastname: Amirian
authors.affiliation: Department of Medicine, Baylor College of Medicine, Houston, TX, United States of America.|Houston Health Services Research and Development Center for Innovations in Quality, Effectiveness and Safety, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX, United States of America.
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Giordano
authors.affiliation: Department of Medicine, Baylor College of Medicine, Houston, TX, United States of America.|Houston Health Services Research and Development Center for Innovations in Quality, Effectiveness and Safety, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX, United States of America.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Richardson
authors.affiliation: Department of Medicine, Baylor College of Medicine, Houston, TX, United States of America.|Houston Health Services Research and Development Center for Innovations in Quality, Effectiveness and Safety, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX, United States of America.
authors.forename: Christine M
authors.initials: CM
authors.lastname: Hartman
authors.affiliation: Department of Medicine, Baylor College of Medicine, Houston, TX, United States of America.|Houston Health Services Research and Development Center for Innovations in Quality, Effectiveness and Safety, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX, United States of America.
authors.forename: Elizabeth Y
authors.initials: EY
authors.lastname: Chiao
mesh_terms: D000328:Adult; D001005:Anus Neoplasms / Q000188:drug therapy* / Q000821:virology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000821:virology; D006678:HIV / Q000187:drug effects / Q000502:physiology; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D011480:Protease Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors; D014728:Veterans / Q000706:statistics & numerical data*
chemical_list: D011480:Protease Inhibitors