title: Toxicity-related antiretroviral drug treatment modifications in individuals starting therapy: a cohort analysis of time patterns, sex, and other risk factors.
abstract: BACKGROUND
  Modifications to combination antiretroviral drug therapy (CART) regimens can occur for a number of reasons, including adverse drug effects. We investigated the frequency of and reasons for antiretroviral drug modifications (ADM) during the first 3 years after initiation of CART, in a closed cohort of CART-naïve adult patients who started treatment in the period 1998-2007 in Croatia.
  
  
  METHODS
  We calculated differential toxicity rates by the Poisson method. In multivariable analysis, we used a discrete-time regression model for repeated events for the outcome of modification due to drug toxicity.
  
  
  RESULTS
  Of 321 patients who started CART, median age was 40 years, 19% were women, baseline CD4 was <200 cells/mm3 in 71%, and viral load was ≥100 000 copies/mL in 69%. Overall, 220 (68.5%) patients had an ADM; 124 (56%) of these had ≥1 ADM for toxicity reasons. Only 12.7% of individuals starting CART in the period 1998-2002 and 39.4% in the period 2003-2007 remained on the same regimen after 3 years. The following toxicities caused ADM most often: lipoatrophy (22%), gastrointestinal symptoms (20%), and neuropathy (18%). Only 5% of drug changes were due to virologic failure. Female sex (hazard ratio [HR], 2.42 95%; confidence intervals, 1.39-4.24) and older age (HR, 1.42 per every 10 years) were associated with toxicity-related ADM in the first 3 months of a particular CART regimen, but after 3 months of CART they were not.
  
  
  CONCLUSIONS
  Less toxic and better-tolerated HIV treatment options should be available and used more frequently in Croatia.
authors.affiliation: University Hospital for Infectious Diseases, Zagreb, Croatia.
authors.forename: Marta
authors.initials: M
authors.lastname: Perović Mihanović
authors.forename: Najm S
authors.initials: NS
authors.lastname: Haque
authors.forename: George W
authors.initials: GW
authors.lastname: Rutherford
authors.forename: Šime
authors.initials: Š
authors.lastname: Zekan
authors.forename: Josip
authors.initials: J
authors.lastname: Begovac
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D015331:Cohort Studies; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D012307:Risk Factors; D012727:Sex Characteristics; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D019380:Anti-HIV Agents