Drug-drug interactions in people living with HIV at risk of hepatic and renal impairment: Current status and future perspectives

Despite the advancement of antiretroviral therapy (ART) for the treatment of human immunodeficiency virus (HIV), drug-drug interactions (DDIs) remain a relevant clinical issue for people living with HIV receiving ART. Antiretroviral (ARV) drugs can be victims and perpetrators of DDIs and a detailed investigation during drug discovery and development is required to determine if dose adjustments are necessary or coadministrations are contraindicated. Maintaining therapeutic ARV plasma concentrations is essential for successful ART and changes resulting from potential DDIs could lead to toxicity, treatment failure or the emergence of ARV resistant HIV. The challenges surrounding DDI management are complex in special populations of people living with HIV and often lack evidence-based guidance due to their underrepresentation in clinical investigations. Specifically, the prevalence of hepatic and renal impairment in people living with HIV are 5 to 10 times greater than HIV-negative people, with each constituting approximately 15% of non-AIDS related mortality. Therapeutic strategies tend to revolve around the treatment of the risk factors which lead to hepatic and renal impairment, such as hepatitis C, hepatitis B, hypertension, hyperlipidaemia and diabetes. These strategies result in a diverse range of potential DDIs with ART. The purpose of this review was two-fold. Firstly, to summarise current pharmacokinetic DDIs and their mechanisms between ARVs and co-medications used for the prevention and treatment of hepatic and renal impairment in people living with HIV. Secondly, to identify existing knowledge gaps surrounding DDIs related to these special populations and suggest areas and techniques to focus future research efforts.

• Population(s)
  • General HIV+ population
• Prevention, Engagement and Care Cascade
  • Engagement and Care Cascade
• Engagement and Care Cascade
  • Treatment
• Co-infections
  • Hepatitis B, C
  • Other
• Health Systems
  • Delivery arrangements