Polypharmacy and Potential Drug–Drug Interactions for People With HIV in the UK From the Climate-HIV Database

C Okoli; A Schwenk; M Radford; M Myland; S Taylor; A Darley; J Barnes; A Fox; F Grimson; I Reeves; S Munshi; A Croucher; N Boxall; P Benn; A Paice; J van Wyk; S Khoo


HIV Medicine. 2020;21(8):471-480. 

In This Article

Abstract and Introduction


Objectives: People with HIV (PWHIV) are likely to need therapies for comorbidities as they age. We assessed risk of drug–drug interactions (DDIs) in PWHIV.

Methods: The Climate-HIV electronic recording system was used to cross-sectionally analyse records from PWHIV aged ≥ 18 years attending four UK HIV units with a current antiretroviral (ARV) prescription in February 2018. Antiretroviral and non-ARV medications were categorized by clinical significance of DDIs (University of Liverpool DDI tool). Potential DDIs were predicted using treatment guidelines for commonly recorded comorbidities.

Results: Among 4630 PWHIV (44% female), 41% were ≥ 50 years old. The average number of non-ARV comedications increased from < 1 for patients aged ≤ 24 years to > 5 for patients aged ≥ 75 years; 65% were taking one or more non-ARV comedications. The median (interquartile range) number of non-ARVs was 1 (0–2) and 2 (1–5) for those aged < 50 and ≥ 50 years, respectively. Common comorbidities/concurrent health conditions occurred more frequently in patients aged ≥ 50 years vs. < 50 (53% vs. 34%). Boosted protease inhibitors were associated with the highest proportion of contraindicated comedications; dolutegravir and raltegravir had the fewest. For non-ARVs, sildenafil and quetiapine were most likely to result in DDIs. Guideline-recommended treatments for hepatitis C, hepatitis B, and tuberculosis had the highest proportions of contraindications when combined with ARV regimens, while treatments for hepatitis C, malignancy, and mental health conditions had the highest proportion of combinations potentially causing DDIs requiring dose monitoring or adjustment.

Conclusions: Non-ARV use by PWHIV is high and increases with age. Treatment decisions for ageing PWHIV should consider guideline recommendations for comorbidities.


The introduction of antiretroviral (ARV) medications has led to substantial increases in the life span of people with HIV (PWHIV).[1] However, as PWHIV live longer, the risk of developing additional health conditions that require concomitant medications increases, and the management of these medications while on combination ARV therapy is a challenging aspect of HIV care.[2] Older PWHIV with comorbidities are routinely prescribed multiple medications and are likely to be managed by several specialist physicians, each focusing on a single aspect of their health.[2,3] This increases the risk of serious adverse drug events and drug–drug interactions (DDIs).[4] Co-administration of multiple medications can also affect adherence and, therefore, effectiveness of treatment if not managed appropriately.[2]

Real-world data indicate that up to 40% of PWHIV have at least one potential DDI involving ARV medications, with interactions between protease inhibitors (PIs) or nonnucleoside reverse transcriptase inhibitors (NNRTIs) and central nervous system or cardiovascular drugs accounting for the majority of DDIs in patients aged ≥ 50 years.[5]

Some potential DDIs can be managed by dose adjustment or monitoring (classified as amber according to the University of Liverpool DDI tool used in this study), requiring ongoing communication between clinicians and from patients. Other DDIs may require a change to alternative therapies for HIV or the associated comorbidities.[6] With the introduction of regimens based on integrase strand transfer inhibitors (INSTIs) such as dolutegravir (DTG), raltegravir (RAL), and bictegravir, opportunities have arisen to reduce the risk of DDIs associated with PIs and NNRTIs.[7] Additionally, using DTG-based two-drug regimens to manage HIV may reduce the risk of associated DDIs.

Recognition of DDIs in real-world settings can be challenging.[8] Care record systems for clinical management of PWHIV are often separate from the main hospital health record for confidentiality reasons, and records of prescriptions issued in general practice or other clinical settings may not be captured reliably. With patients living longer and having greater access to medicines (including online, over-the-counter, and prescribed by healthcare professionals), there is an increased risk of DDIs when prescribing ARV medications without an accurate and up-to-date drug history. Real-world analyses of prescriptions of concomitant medication and DDIs with ARV therapy are generally lacking, particularly in women and minorities. The purpose of this study was to evaluate the types of concomitant medications used with ARV therapy and to explore the risk of DDIs associated with common comorbidities and ARV medications in a real-world heterogeneous population.