Treatment Modification in Human Immunodeficiency Virus-Infected Individuals Starting Combination Antiretroviral Therapy Between 2005 and 2008

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, 19.525.6) 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 (1.2.1. [1.03-1.40] per 10-year increase; P=.02), female sex (1.68 [1.14-2.48]; P=.009), non-white ethnicity (1.71 [1.18-2.47]; P=.005), higher baseline CD4 cell count (1,19 [1.10-1.28] per 100/mu L 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.