Background Antiretroviral treatment (ART) has significantly increased the life expectancy of human immunodeficiency virus (HIV)-infected individuals. However, toxicities, comorbidities and treatment failures, among others, may result in frequent ART regimen changes. Purpose To identify and analyse the ART changes and the reasons for them in HIV-infected patients over a 42-month period of study in our hospital. Materials and methods A retrospective observational study was conducted over 42 months in all outpatients on antiretroviral treatment who attended our hospital for HIV monitoring between January 2010 and June 2013. For each patient whose ART was changed we recorded the following data in a database: sex, age, previous and new treatment, reason for treatment change and resistance profile. Data was tabulated using Excel. Results During the period of study, a total of 528 patients changed ART (78% men, mean age 47 ± 7.6 years). The most common cause of change was adverse drug reactions (ADR) (47.5%). The most usual ADR were: gastrointestinal symptoms (48 patients), neuropsychiatric disorders (44 patients), renal disease (33 patients), dyslipidaemia (27 cases) and liver disease (24 cases). The drugs which caused ADR were efavirenz (8.0%), tenofovir (7.2%), atazanavir (6.3%), didanosine (6.1%) and lopinavir/ritonavir (4.4%). Other reasons for ART change were: simplification (14.6%), resistance (10.2%), treatment failure (5.5%), inclusion in a clinical trial (4.4%); and other causes (non-compliance, interactions, pregnancy, clinical decision, dose change and unknown). The most common treatment regimen before the change was tenofovir/emtricitabine/efavirenz (TDF/FTC/EFV). After the change, tenofovir/emtricitabine (TDF/FTC) plus darunavir/ritonavir (DRV/r) was the most usual regimen. Conclusions The study revealed that a large percentage of ART changes were due to ADR. The intervention of hospital pharmacists could play an important role in the overall monitoring of HIV patients. No conflict of interest.