Objective This study was to determine and compare the prevalences of polypharmacy and comorbidities in patients aged 50 years or older with those patients younger than 50 years in a Mexican population. Results One hundred and twenty-five patients were enrolled, 60 (48%) were aged 50 years or older. The median CD4+ cell counts were 509 cells/μL (interquartile range [IQR]: 324–730) for the older patients and 384 cells/μL (IQR: 262–562) ( P = 0.021) for the younger patients. Viral suppression were significantly higher in the older group: 80% vs. 63% ( P = 0.037). The number of comorbidities was significantly higher in the older group, with a median of 2 (IQR: 2–3) vs. 1 (IQR: 0–1) ( P ≤ 0.001). After adjustment of the logistic regression model in the older group, the following comorbidities differed between the age groups: systemic arterial hypertension (odds ratio [OR]: 15.75; 95% confidence interval [CI] 3.49–71.05; P = < 0.001), diabetes mellitus (OR: 14.36; 95% CI 1.79–115.07; P = 0.001), osteoarthritis (OR: 10.33; 95% CI 2.88–37.05; P = < 0.001), hyperlipidemia (OR: 2.78; 95% CI 1.22–6.34; P = 0.001), and polypharmacy (OR: 6.58; 95% CI 3.01–14.39; P = 0.001).