title: Long-term exposure to combination antiretroviral therapy and risk of death from specific causes:  no evidence for any previously unidentified increased risk due to antiretroviral therapy.
abstract: BACKGROUND
  Despite the known substantial benefits of combination antiretroviral therapy (cART), cumulative adverse effects could still limit the overall long-term treatment benefit. Therefore we investigated changes in the rate of death with increasing exposure to cART.
  
  
  METHODS
  A total of 12 069 patients were followed from baseline, which was defined as the time of starting cART or enrolment into EuroSIDA whichever occurred later, until death or 6 months after last follow-up visit. Incidence rates of death were calculated per 1000 person-years of follow-up (PYFU) and stratified by time of exposure to cART (≥3 antiretrovirals): less than 2, 2-3.99, 4-5.99, 6-7.99 and more than 8 years. Duration of cART exposure was the cumulative time actually receiving cART. Poisson regression models were fitted for each cause of death separately.
  
  
  RESULTS
  A total of 1297 patients died during 70,613 PYFU [incidence rate 18.3 per 1000 PYFU, 95% confidence interval (CI) 17.4-19.4], 413 due to AIDS (5.85, 95% CI 5.28-6.41) and 884 due to non-AIDS-related cause (12.5, 95% CI 11.7-13.3). After adjustment for confounding variables, including baseline CD4 cell count and HIV RNA, there was a significant decrease in the rate of all-cause and AIDS-related death between 2 and 3.99 years and longer exposure time. In the first 2 years on cART the risk of non-AIDS death was significantly lower, but no significant difference in the rate of non-AIDS-related deaths between 2 and 3.99 years and longer exposure to cART was observed.
  
  
  CONCLUSIONS
  In conclusion, we found no evidence of an increased risk of both all-cause and non-AIDS-related deaths with long-term cumulative cART exposure.
authors: Copenhagen HIV Programme, University of Copenhagen, Denmark. jko@cphiv.dk
authors: Justyna D
authors: JD
authors: Kowalska
authors: Joanne
authors: J
authors: Reekie
authors: Amanda
authors: A
authors: Mocroft
authors: Peter
authors: P
authors: Reiss
authors: Bruno
authors: B
authors: Ledergerber
authors: Jose
authors: J
authors: Gatell
authors: Antonella
authors: A
authors: d'Arminio Monforte
authors: Andrew
authors: A
authors: Phillips
authors: Jens D
authors: JD
authors: Lundgren
authors: Ole
authors: O
authors: Kirk
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000401:mortality; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000009:adverse effects*; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects; D018791:CD4 Lymphocyte Count; D002423:Cause of Death; D015897:Comorbidity; D018450:Disease Progression; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D015497:HIV-1 / Q000302:isolation & purification*; D006509:Hepatitis B / Q000401:mortality; D006526:Hepatitis C / Q000401:mortality; D006801:Humans; D006973:Hypertension / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012367:RNA, Viral; D012307:Risk Factors; D012907:Smoking / Q000401:mortality; D013997:Time Factors; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D012367:RNA, Viral