Toxicity is the most frequently reported reason for modifying or discontinuing the first com-bined antiretroviral therapy regimens, and it can cause significant morbidity, poor qualityof life and also can be an important barrier to adherence, ultimately resulting in treatmentfailure and viral resistance. Elderly patients with HIV/AIDS (≥50 years) may have a differ-ent profile in terms of treatment modification due to higher incidence of comorbidities andpolypharmacy. The aim of this study was to describe the incidence of modifying or discon-tinuing first combined antiretroviral therapy regimen due to toxicity (TOX-MOD) during thefirst year of treatment at the IPEC – FIOCRUZ HIV/AIDS cohort, Rio de Janeiro, Brazil, strat-ified by age. Demographic, clinical and treatment characteristics from antiretroviral-naïvepatients who first received combined antiretroviral therapy between Jan/1996 and Dec/2010were collected. Incidence rate and confidence interval of each event were estimated usingquasipoisson model. To estimate hazard ratio (HR) of TOX-MOD during the first year of com-bined antiretroviral therapy Cox’s proportional hazards regression was applied. Overall, 1558patients were included; 957 (61.4%), 420 (27.0%) and 181 (11.6%) were aged <40, 40–49, and≥50 years, respectively. 239 (15.3%) events that led to any modifying or discontinuing withinthe first year of treatment were observed; 228 (95.4%) of these were TOX-MOD, correspondingto an incidence rate of 16.6/100 PY (95% CI: 14.6–18.9). The most frequent TOX-MOD duringfirst combined antiretroviral therapy regimen were hematologic (59; 26.3%), central ner-vous system (47; 20.9%), rash (42; 19.1%) and gastrointestinal (GI) (38; 16.7%). In multivariateanalysis, incidence ratio of TOX-MOD during the first year of combined antiretroviral ther-apy progressively increases with age, albeit not reaching statistical significance. This profilewas maintained after adjusting the model for sex, combined antiretroviral therapy regimenand year of combined antiretroviral therapy initiation. These results are important becausenot only patients are living longer and aging with HIV, but also new diagnoses are being made among the elderly. Prospective studies are needed to evaluate the safety profile of first line combined antiretroviral therapy on elderly individuals, especially in resource-limited countries, where initial regimens are mostly NNRTI-based.