title: NNRTI-based antiretroviral therapy may increase risk of radiation induced side effects in HIV-1-infected patients.
abstract: OBJECTIVE
  As the incidence of cancer is rising in HIV-1-infected patients, radiotherapy is used more frequently in this patient group. Strong radiation induced side effects have been reported in single patients on antiretroviral therapy. Thus we investigated whether HIV-1 itself or antiretroviral drugs could enhance radiosensitivity in patients.
  
  
  METHODS
  Radiosensitivity after in vitro irradiation of blood lymphocytes was tested in 196 individuals (80 HIV-1-infected patients and 116 healthy controls and cancer patients) using a three color fluorescence in situ hybridization approach to analyze chromosomal aberrations (B/M). Additionally, the NNRTI efavirenz and the NRTIs tenofovir and emtricitabine were tested for radiosensitizing effects in vitro.
  
  
  RESULTS
  Lymphocytes from HIV-1-infected patients in the NNRTI + NRTI group were significantly more sensitive to ionizing radiation than in the other groups (patients without treatment or with NRTI + PI or HIV-negative controls). In vitro the triple medication efavirenz, tenofovir and emtricitabine leads to a reduced survival fraction and an increased activation of the DNA repair proteins H2AX, Nbs, Atm and 53BP1 in combination with ionizing radiation.
  
  
  CONCLUSIONS
  HIV-1 treatment with NNRTI containing therapy regimes possibly sensitizes a subgroup of patients to ionizing radiation. Individual radiosensitivity of HIV-1-infected patients on HAART including NNRTI should be tested before starting radiotherapy.
authors.affiliation: Department of Radiation Oncology, University Hospital Erlangen, Friedrich-Alexander-University of Erlangen-Nürnberg, Germany.
authors.forename: Keller
authors.initials: K
authors.lastname: Ulrike
authors.affiliation: Department of Radiation Oncology, University Hospital Erlangen, Friedrich-Alexander-University of Erlangen-Nürnberg, Germany.
authors.forename: Hecht
authors.initials: H
authors.lastname: Markus
authors.affiliation: Department of Internal Medicine 3, University Hospital Erlangen, Friedrich-Alexander-University of Erlangen-Nürnberg, Germany.
authors.forename: Harrer
authors.initials: H
authors.lastname: Thomas
authors.affiliation: Department of Internal Medicine 3, University Hospital Erlangen, Friedrich-Alexander-University of Erlangen-Nürnberg, Germany.
authors.forename: Harrer
authors.initials: H
authors.lastname: Ellen
authors.affiliation: Department of Radiation Oncology, University Hospital Erlangen, Friedrich-Alexander-University of Erlangen-Nürnberg, Germany.
authors.forename: Schuster
authors.initials: S
authors.lastname: Barbara
authors.affiliation: Department of Radiation Oncology, University Hospital Erlangen, Friedrich-Alexander-University of Erlangen-Nürnberg, Germany.
authors.forename: Fietkau
authors.initials: F
authors.lastname: Rainer
authors.affiliation: Department of Radiation Oncology, University Hospital Erlangen, Friedrich-Alexander-University of Erlangen-Nürnberg, Germany. Electronic address: Luitpold.Distel@uk-erlangen.de.
authors.forename: Luitpold V
authors.initials: LV
authors.lastname: Distel
mesh_terms: D019380:Anti-HIV Agents / Q000009:adverse effects*; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects; D002869:Chromosome Aberrations; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1; D006801:Humans; D008214:Lymphocytes / Q000528:radiation effects*; D011836:Radiation Tolerance; D012306:Risk
chemical_list: D019380:Anti-HIV Agents
keywords: Cancer; HAART; HIV; NNRTI; Radiosensitivity; Radiotherapy