Abstract Objective The study objective was to analyze the characteristics and the response to therapy in the eldest of the older adults living with human immunodeficiency virus. Methods The study included a cohort of patients with human immunodeficiency virus aged 55 years or more on initiating highly active antiretroviral therapy (HAART). Immunologic and virologic response, morbidity, and mortality were assessed. Patients were categorized as aged less than 65 years and 65 years or more. Results A total of 112 patients were included (82 patients aged < 65 years and 30 patients aged ≥ 65 years). There were no differences between the age groups in baseline characteristics, survival, and virologic response. There was a trend toward better adherence and a lower CD4+ cell increase after HAART in the older group. Conclusion A relationship was found between lower CD4+ cell increase after HAART and advanced age. We found the best adherence to treatment in the eldest of the older adults, and this has been shown to be the only protective independent factor related to virologic failure.