title: Medication safety in patients taking antiretrovirals at three diverse sites in central Uganda: an in-depth study, including feasibility of a novel medication safety feedback loop
Creators: name: Seden, Kay
Publisher: name: University of Liverpool Repository
Year: 2023

description: Introduction

In Sub-Saharan Africa (SSA) a public health approach is deployed to maximise health gains for the population, in contrast to developed countries. The true prevalence of medication error in antiretroviral (ARV) programs in SSA has never been systematically evaluated, though it is likely to pose a considerable threat to programmatic success. Lack of routine laboratory monitoring, ARV deployment to district level, a high background of overlapping syndromes and relative lack of medical personnel may all contribute to medication safety issues. ‘Vertical’ (unintegrated) health programs pose high risk for unrecognised drug-drug interactions (DDIs) with ARVs, as complete medication histories may be lacking. In Europe, prescribing errors affect up to 20% of inpatients taking ARVs, with DDIs affecting 14-41%. We reported poor medication history recording, adherence assessment and DDI recognition by doctors in the UK. No previous studies in a low resource setting have characterised the extent to which medication safety issues cause actual patient harm and impact the effectiveness of ARV programs.
This observational study in Uganda aimed to determine the prevalence and harm caused by medication safety issues in patients taking ARVs, and to assess a novel medication safety feedback loop for feasibility and clinical utility. Data used to generate DDI recommendations comes from various sources. A benchmark was developed for quality of evidence related to DDI studies and recommendations.

Methods

Guided by the principles of WHO GRADE methodology, a systematic review of DDI data (HIV and malaria treatment) was used to develop and test a transparent, structured framework for generating evidence quality summaries for DDIs. 
A cross-sectional, observational study of 2000 consecutive patients receiving ARVs at the Infectious Diseases Institute, Kampala screened the most recent prescription for each patient for clinically significant DDIs using www.hiv-druginteractions.org. 
This study informed the design of a longitudinal study where trained pharmacy technicians at three diverse clinics across Uganda obtained detailed medication histories using patient report, clinical notes and prescriptions. Prescribed and purchased medicines from any source were included, and patients were screened for adverse drug events (ADEs). Information was transferred via secure mobile upload with tablet devices to an ARV information resource, who screened for DDIs using www.hiv-druginterctions.org, and generated medication safety feedback for prescribers. Prescribers documented at baseline whether they were aware of DDIs for each patient. At the next patient clinic visit, prescribers assessed acceptability and clinical utility of the medication safety feedback via anonymous questionnaire. 

Results

The systematic review included 36 articles and conference presentations published between 1987-August 2016. There is significant risk of DDIs between HIV protease inhibitors, or non-nucleoside reverse transcriptase inhibitors and artemesinin-containing antimalarial regimens. For many ARVs, DDI studies with antimalarials were lacking, and the majority were of moderate to very low quality. Quality of evidence and strength of recommendation categories were defined and developed specifically for recommendations concerning DDIs.
Clinically significant DDIs (CSDDIs) were detected in 18.7% of 2000 outpatients taking ARVs at one large centre of excellence in Kampala, detected through prescription review alone. 
In the longitudinal study, when full medication histories were taken for 500 patients across 3 sites, 26.2% of patients had one or more CSDDI. 25% of the CSDDIs detected were related to medicines sourced from outside the clinic. Prescribers reported being aware of only 4.6% of CSDDIs. Prescribers reported that active DDI screening and feedback provided new information in 60.2% of cases, and that they changed their management as a result in 55.6% of cases. DDI checks reportedly added benefit in 74.8% of cases. 
Of 300 patients taking efavirenz (EFV)-based ARVs, 36% were affected by persisting nervous system/psychiatric ADEs (median duration 22 months). Dizziness affected 27.3% of patients taking EFV. Severity of the ADEs was rated by patients at ≥5/10 in 76 (58.5%) cases. In 95 (86%) cases, there was no record of the ADEs in the clinical notes. 

Discussion

The application of a quality of evidence and strength of recommendation guideline approach to managing DDIs is feasible.
DDI screening using patient interview showed CSDDI prevalence ~10% higher than observed with prescription review alone. The novel DDI screening and feedback loop was feasible, reportedly acceptable to prescribers and added benefit in &gt;70% of cases. Longitudinal follow up will inform whether the DDI feedback loop can improve patient outcomes and demonstrate cost-benefit. A system where pharmacists or pharmacy technicians routinely discuss medication use with patients allows detection and monitoring of adverse events. Asking patients to rate severity of their adverse events gave an insight into the impact on their quality of life.