Human immunodeficiency virus (HIV) is a major public health issue. UNAIDS report that 39.9 million people globally were living with HIV in 2023, 1.3 million people became newly infected and 630,000 people died from AIDS-related illnesses in that same year.

The pharmacological and clinical management of HIV therapy can be complex due to comorbidities and people living with HIV often use multiple medications, which leads to an increased risk of drug-drug interactions (DDIs).

Many drug combinations have the potential to interact, and this can affect patient safety or the effectiveness of treatment. Therefore, some drug combinations should not be given at all, while other drugs may be used together with caution. Prescribers need access to regularly updated, evidence-based information to manage these treatment complexities safely and effectively.

Challenge

DDIs are where a combination of drugs can interact in a negative way, creating unwanted reactions. They are a major cause of harm for people on HIV treatment, affecting as many as 25% of people.

The University of Liverpool recognised this danger for those undergoing HIV and hepatitis treatments and was the first to report harmful DDIs involving HIV-TB coinfection as well as the beneficial boosting of HIV protease inhibitors.

Solution

Between 2012 and 2018, the University participated in large-scale studies to characterise the frequency and severity of DDIs worldwide. Of approximately 39,000 patients from the UK, Switzerland, Spain and Uganda, significant DDIs were reported in 18-35% of patients taking antiretrovirals.

DDIs with the highest risk and greatest consequence involved: antibiotics, antifungals, central nervous system drugs, cardiovascular drugs and corticosteroids. The expertise gained from this research enabled the team to develop an electronic point-of-care HIV drug interaction tool in 2000, providing prescribing support in the form of interaction recommendations on the likelihood of DDIs between HIV drugs and commonly prescribed co-medications.

Each tool developed has a disease-specific focus, working to clinical and scientific expertise, allowing for greater coverage than other DDI resources, built upon the systematic evaluation of over 80,000 DDIs across all tools, providing detailed DDI commentaries for each interaction.

The team works with patient advocacy groups, such as i-Base, to determine the most appropriate and informative ways to provide drug information to patient audiences, so the tools are available in many formats, ensuring they can be accessible to as many healthcare professionals, researchers, and patients as possible, including drug interaction websites and mobile apps for each disease area.

Impact

The tools are used globally – they are standard of care in over 30 countries – and have been integrated into electronic prescribing systems in Australia and Uganda, while a Japanese version of the hepatology tool was launched in 2017, followed by Spanish and Portuguese versions of the HIV tool in 2021.

Between January 2017 and December 2019, over 17,500,000 interactions have been returned from 50,000 unique monthly users across 220 countries and territories. The tools identify missed DDIs in up to 95% of prescriptions and change clinical management in 55% of cases resulting in demonstrable economic benefit.

The Liverpool tools are recommended for use in every HIV clinic in the UK, have established users across Western Europe and North America, and are increasingly used in Latin America, Asia and Africa.

This reputation is demonstrated by comments from the Chair of the WHO HIV Guideline Review Committee, who stated that: “WHO recognises the Liverpool HIV Drug Interactions website to be a world-leading resource… We rely on the information provided to develop global guidelines for the treatment and care of people living with HIV and are very grateful to be able to reproduce the information from this site in our guidelines.”

The need to provide improved DDI education was also identified, and the University has developed and hosted educational events, demonstrating the utility of the tools to aid clinical management. These have included symposia sessions at HIV Glasgow and the European AIDS Conference as well as several online sessions and workshops for global audiences.

By identifying and addressing knowledge gaps in both drug interaction studies and DDI education, the University has contributed to changes in drug labelling and clinical behaviour, resulting in changes to clinical practice.

Building on the experience gained from developing HIV and hepatology prescribing tools, the University identified a clinical need to expand the suite of tools to include cancer (2017) and COVID-19 (2020).

Links

• Pioneering tools for managing drug-drug interactions in HIV and hepatitis