title: Treatment modification in human immunodeficiency virus-infected individuals starting combination antiretroviral therapy between 2005 and 2008.
abstract: BACKGROUND
  Adverse effects of combination antiretroviral therapy (CART) commonly result in treatment modification and poor adherence.
  
  
  METHODS
  We investigated predictors of toxicity-related treatment modification during the first year of CART in 1318 antiretroviral-naive human immunodeficiency virus (HIV)-infected individuals from the Swiss HIV Cohort Study who began treatment between January 1, 2005, and June 30, 2008.
  
  
  RESULTS
  The total rate of treatment modification was 41.5 (95% confidence interval [CI], 37.6-45.8) per 100 person-years. Of these, switches or discontinuations because of drug toxicity occurred at a rate of 22.4 (95% CI, 19.5-25.6) per 100 person-years. The most frequent toxic effects were gastrointestinal tract intolerance (28.9%), hypersensitivity (18.3%), central nervous system adverse events (17.3%), and hepatic events (11.5%). In the multivariate analysis, combined zidovudine and lamivudine (hazard ratio [HR], 2.71 [95% CI, 1.95-3.83]; P < .001), nevirapine (1.95 [1.01-3.81]; P = .050), comedication for an opportunistic infection (2.24 [1.19-4.21]; P = .01), advanced age (1.21 [1.03-1.40] per 10-year increase; P = .02), female sex (1.68 [1.14-2.48]; P = .009), nonwhite ethnicity (1.71 [1.18-2.47]; P = .005), higher baseline CD4 cell count (1.19 [1.10-1.28] per 100/microL increase; P < .001), and HIV-RNA of more than 5.0 log(10) copies/mL (1.47 [1.10-1.97]; P = .009) were associated with higher rates of treatment modification. Almost 90% of individuals with treatment-limiting toxic effects were switched to a new regimen, and 85% achieved virologic suppression to less than 50 copies/mL at 12 months compared with 87% of those continuing CART (P = .56).
  
  
  CONCLUSIONS
  Drug toxicity remains a frequent reason for treatment modification; however, it does not affect treatment success. Close monitoring and management of adverse effects and drug-drug interactions are crucial for the durability of CART.
authors.affiliation: University Hospital Basel, Switzerland.
authors.forename: Luigia
authors.initials: L
authors.lastname: Elzi
authors.forename: Catia
authors.initials: C
authors.lastname: Marzolini
authors.forename: Hansjakob
authors.initials: H
authors.lastname: Furrer
authors.forename: Bruno
authors.initials: B
authors.lastname: Ledergerber
authors.forename: Matthias
authors.initials: M
authors.lastname: Cavassini
authors.forename: Bernard
authors.initials: B
authors.lastname: Hirschel
authors.forename: Pietro
authors.initials: P
authors.lastname: Vernazza
authors.forename: Enos
authors.initials: E
authors.lastname: Bernasconi
authors.forename: Rainer
authors.initials: R
authors.lastname: Weber
authors.forename: Manuel
authors.initials: M
authors.lastname: Battegay
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy / Q000453:epidemiology; D000225:Adenine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D000328:Adult; D000480:Alkynes; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects*; D000069446:Atazanavir Sulfate; D048588:Benzoxazines / Q000008:administration & dosage / Q000009:adverse effects; D003521:Cyclopropanes; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D015224:Dideoxynucleosides / Q000008:administration & dosage / Q000009:adverse effects; D004359:Drug Therapy, Combination; D000068679:Emtricitabine; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage / Q000009:adverse effects; D061466:Lopinavir; D008297:Male; D008875:Middle Aged; D019829:Nevirapine / Q000008:administration & dosage / Q000009:adverse effects; D009842:Oligopeptides / Q000008:administration & dosage / Q000009:adverse effects; D063065:Organophosphonates / Q000008:administration & dosage / Q000009:adverse effects; D016016:Proportional Hazards Models; D011446:Prospective Studies; D011725:Pyridines / Q000008:administration & dosage / Q000009:adverse effects; D011744:Pyrimidinones / Q000008:administration & dosage / Q000009:adverse effects; D012307:Risk Factors; D013557:Switzerland / Q000453:epidemiology; D000068698:Tenofovir; D015215:Zidovudine / Q000008:administration & dosage / Q000009:adverse effects; D000099227:Abacavir
chemical_list: D000225:Adenine; D000480:Alkynes; D019380:Anti-HIV Agents; D000069446:Atazanavir Sulfate; D048588:Benzoxazines; D003521:Cyclopropanes; D003841:Deoxycytidine; D015224:Dideoxynucleosides; D000068679:Emtricitabine; D019259:Lamivudine; D061466:Lopinavir; D019829:Nevirapine; D009842:Oligopeptides; D063065:Organophosphonates; D011725:Pyridines; D011744:Pyrimidinones; D000068698:Tenofovir; D015215:Zidovudine; D000099227:Abacavir; C098320:efavirenz