Development of an evidence evaluation and synthesis system for drug-drug interactions, and its application to a systematic review of HIV and malaria co-infection.
BACKGROUND
In all settings, there are challenges associated with safely treating patients with multimorbidity and polypharmacy. The need to characterise, understand and limit harms resulting from medication use is therefore increasingly important. Drug-drug interactions (DDIs) are prevalent in patients taking antiretrovirals (ARVs) and if unmanaged, may pose considerable risk to treatment outcome. One of the biggest challenges in preventing DDIs is the substantial gap between theory and clinical practice. There are no robust methods published for formally assessing quality of evidence relating to DDIs, despite the diverse sources of information. We defined a transparent, structured process for developing evidence quality summaries in order to guide therapeutic decision making. This was applied to a systematic review of DDI data with considerable public health significance: HIV and malaria.


RESULTS
This was a systematic review of DDI data between antiretrovirals and drugs used in prophylaxis and treatment of malaria. The data comprised all original research in humans that evaluated pharmacokinetic data and/or related adverse events when antiretroviral agents were combined with antimalarial agents, including healthy volunteers, patients with HIV and/or malaria, observational studies, and case reports. The data synthesis included 36 articles and conference presentations published via PubMed and conference websites/abstract books between 1987-August 2016. There is significant risk of DDIs between HIV protease inhibitors, or NNRTIs and artemesinin-containing antimalarial regimens. For many antiretrovirals, 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.


CONCLUSIONS
There is significant potential for DDIs between antiretrovirals and antimalarials. The application of quality of evidence and strength of recommendation criteria to DDI data is feasible, and allows the assessment of DDIs to be robust, consistent, transparent and evidence-based.
Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom.
Kay
K
Seden
Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom.
Sara
S
Gibbons
Division of Infectious Diseases and Hospital Epidemiology, Departments of Medicine and Clinical Research, University Hospital of Basel, Basel, Switzerland.
Catia
C
Marzolini
National Hemophilia Center, Sheba Medical Center, Ramat Gan, Israel.
Jonathan M
JM
Schapiro
Department of Pharmacy & Radboud Institute of Health Sciences (RIHS), Radboud University Medical Centre, Nijmegen, the Netherlands.
David M
DM
Burger
Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom.
David J
DJ
Back
Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom.
Saye H
SH
Khoo
D000962:Antimalarials / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D060085:Coinfection / Q000188:drug therapy*; D004347:Drug Interactions; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D008288:Malaria / Q000188:drug therapy*; D019338:Polypharmacy; D015995:Prevalence; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use
D000962:Antimalarials; D018501:Antirheumatic Agents; D018894:Reverse Transcriptase Inhibitors