The effectiveness of antiretroviral therapy has significantly improved life expectancy of HIV-infected individuals. Global campaigns and awareness programmes have led to substantial drop in the rate of new infections. Consequently, the proportion of ageing HIV-infected individuals continues to increase. HIV-associated and age-related comorbidity necessitates polypharmacy in ageing individuals living with HIV/AIDS. The risk of drug-drug interaction increases with the number of administered drugs. Agerelated changes in the body physiology are known to influence pharmacokinetic and pharmacodynamic profile of administered drugs. These changes include reduction in blood flow to major organs, decline in metabolic activities, body mass shrinking and changes in body water and fat proportion. These factors contribute to the perceived and reported higher incidence of drug-drug interaction in this population. The current paper reviews the reported incidence of drug-drug interactions in ageing HIVinfected individuals, providing relative mechanisms and possible factors responsible in comparison to younger population. Health professionals should be aware of the drug interaction risks involved in the management of HIV/AIDS in the ageing population; be able to anticipate them based on concomitant medications and manage them as necessary.