The HIV-infected population is aging, and the concomitant comorbidities increase the likelihood of polypharmacy. There is a scarcity of data for determining drug-related problems in people living with HIV/AIDS (PLWHA). Materials and methods: This cross-sectional study was carried out between 1 September 2015 and 1 July 2016. All patients underwent a face-to-face interview with a clinical pharmacist. PCNE Classification V 7.0 was used classify incident drug-related problems (DRPs). Results: The mean age of the patients was 40.4 ± 13.06 years. The rate of polypharmacy was 66.1% in patients with comorbidities and 12.3% in those without comorbidities (P < 0.001). DRPs were more prominent in older patients (46 vs. 37 years, P < 0.001), those with longer durations of antiretroviral therapy (ART) (45 vs. 27 months, P = 0.014), and those with lower education levels (P = 0.013). Receiving >3 ART drugs was associated with more DRPs in the logistic regression model (odds ratio: 8.299, 95% confidence interval: 1.924-35.803). Fifty-eight interventions were performed in 45 (24.9%) patients. Clinical pharmacist interventions were performed in 18.9% of patients without polypharmacy and in 38.9% of patients with polypharmacy (P < 0.001). Conclusion: DRPs and polypharmacy are common among elderly PLWHA. More interventions are warranted to boost the quality of life in aging PLWHA.