Toxicity-related antiretroviral drug treatment modifications in individuals starting therapy: a cohort analysis of time patterns, sex, and other risk factors.

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-nave adult patients who started treatment in the period 1998-2007 in Croatia. Material/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/mm(3) 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.