title: Exposure to antiretroviral therapy and risk of cancer in HIV-infected persons.
abstract: OBJECTIVE
  The incidence of certain non-AIDS-defining cancers (NADCs) in HIV patients has been reported to have increased in the combination antiretroviral therapy (ART) era. Studies are needed to directly evaluate the effect of ART use on cancer risk.
  
  
  METHODS
  We followed 12 872 HIV-infected Kaiser Permanente members whose complete ART history was known for incident cancers between 1996 and 2008.
  
  
  METHODS
  Cancers, identified from Surveillance, Epidemiology, and End Results (SEER)-based cancer registries, were grouped as ADCs, infection-related NADCs, or infection-unrelated NADCs. We also evaluated the most common individual cancer types. Rate ratios for ART use (yes/no) and cumulative duration of any ART, protease inhibitor, and nonnucleotide reverse transcriptase inhibitor (NNRTI) therapy were obtained from Poisson models adjusting for demographics, pretreatment or recent CD4 cell count and HIV RNA levels, years known HIV-infected, prior antiretroviral use, HIV risk, smoking, alcohol/drug abuse, overweight/obesity, and calendar year.
  
  
  RESULTS
  The cohort experienced 32 368 person-years of ART, 21 249 person-years of protease inhibitor therapy, and 15 643 person-years of NNRTI therapy. The mean follow-up duration was 4.5 years. ADC rates decrease with increased duration of ART use [rate ratio per year = 0.61 (95% confidence interval 0.56-0.66)]; the effect was similar by therapy class. ART, protease inhibitor, or NNRTI therapy duration was not associated with infection-related or infection-unrelated NADC [rate ratio per year ART = 1.00 (0.91-1.11) and 0.96 (0.90-1.01), respectively], except a higher anal cancer risk with longer protease inhibitor therapy [rate ratio per year = 1.16 (1.02-1.31)].
  
  
  CONCLUSIONS
  No therapy class-specific effect was found for ADC. ART exposure was generally not associated with NADC risk, except for long-term use of protease inhibitor, which might be associated with increased anal cancer risk.
authors.affiliation: Kaiser Permanente Southern California, Pasadena, CA, USA.
authors.forename: Chun
authors.initials: C
authors.lastname: Chao
authors.forename: Wendy A
authors.initials: WA
authors.lastname: Leyden
authors.forename: Lanfang
authors.initials: L
authors.lastname: Xu
authors.forename: Michael A
authors.initials: MA
authors.lastname: Horberg
authors.forename: Daniel
authors.initials: D
authors.lastname: Klein
authors.forename: William J
authors.initials: WJ
authors.lastname: Towner
authors.forename: Charles P
authors.initials: CP
authors.lastname: Quesenberry
authors.forename: Donald I
authors.initials: DI
authors.lastname: Abrams
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Silverberg
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000150:complications* / Q000188:drug therapy* / Q000453:epidemiology; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects*; D001005:Anus Neoplasms / Q000139:chemically induced / Q000453:epidemiology; D018791:CD4 Lymphocyte Count; D002140:California / Q000453:epidemiology; D015331:Cohort Studies; D015897:Comorbidity; D005260:Female; D005500:Follow-Up Studies; D015497:HIV-1 / Q000302:isolation & purification; D006801:Humans; D015994:Incidence; D008297:Male; D009369:Neoplasms / Q000139:chemically induced* / Q000453:epidemiology* / Q000821:virology; D011480:Protease Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D012042:Registries; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D012307:Risk Factors; D018426:SEER Program; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D011480:Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors