title: Highly active antiretroviral therapy and the incidence of non-AIDS-defining cancers in people with HIV infection.
abstract: OBJECTIVE
  The effect of highly active antiretroviral therapy (HAART) on the incidence of non-AIDS-defining cancers (NADCs) is unclear.
  
  
  METHODS
  We have investigated the occurrence of NADCs in a prospective cohort of 11,112 HIV-positive individuals, with 71,687 patient-years of follow-up. Standardized incidence ratios (SIRs) were calculated using general population incidence data. We investigated the effect of calendar period, HIV parameters, and immunologic and treatment-related factors on the incidence of these cancers using univariate and multivariate analyses.
  
  
  RESULTS
  The SIR for all NADCs was 1.96 (95% CI, 1.66 to 2.29). There was no significant excess in incidence in the pre-HAART era (1983 to 1995; SIR, 0.95; 95% CI, 0.58 to 1.47). However, the incidence increased in the early HAART period (1996 to 2001) and remains elevated in the most recent established HAART period (2002 to 2007; SIR, 2.05; 95% CI, 1.51 to 2.72, and SIR 2.49; 95% CI, 2.00 to 3.07, respectively). Multivariate analysis showed that use of HAART (hazard ratio [HR] = 1.64; 95% CI, 1.13 to 2.39) and a nadir CD4 count less than 200/microL (HR = 1.67; 95% CI, 1.10 to 2.54) were associated with an increased risk. Only the non-nucleoside reverse transcriptase inhibitors (NNRTIs) were associated with a significantly increased risk of NADCs (HR = 1.45; 95% CI, 1.01 to 2.08). Much of this association was attributable to an increased risk of Hodgkin's lymphoma with NNRTIs (HR = 2.20; 95% CI, 1.03 to 4.69).
  
  
  CONCLUSIONS
  Since the introduction of HAART, there has been a significantly increased risk of NADCs, which has now stabilized. A number of factors are associated with this increased risk, including HAART use. There may be an association between the use of NNRTIs and the development of Hodgkin's lymphoma.
authors.affiliation: Department of Medical Oncology, St Bartholomew's Hospital, Little Brittain, London EC1A7BE, United Kingdom. thomas.powles@bartsandthelondon.nhs.uk
authors.forename: Thomas
authors.initials: T
authors.lastname: Powles
authors.forename: David
authors.initials: D
authors.lastname: Robinson
authors.forename: Justin
authors.initials: J
authors.lastname: Stebbing
authors.forename: Jonathan
authors.initials: J
authors.lastname: Shamash
authors.forename: Mark
authors.initials: M
authors.lastname: Nelson
authors.forename: Brian
authors.initials: B
authors.lastname: Gazzard
authors.forename: Sundhiya
authors.initials: S
authors.lastname: Mandelia
authors.forename: Henrik
authors.initials: H
authors.lastname: Møller
authors.forename: Mark
authors.initials: M
authors.lastname: Bower
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects*; D015331:Cohort Studies; D015897:Comorbidity; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D008297:Male; D009369:Neoplasms / Q000139:chemically induced / Q000453:epidemiology*
chemical_list: D019380:Anti-HIV Agents