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No Drop in Rate of Drug-Drug
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Interactions With HIV Drugs Since 1985
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International Workshop on Clinical Pharmacology of HIV, Hepatitis and Other Antiviral Drugs, September 20-22, 2021
By Mark Mascolini for NATAP and Virology Education
Although experts consider modern antiretrovirals less prone to clinically significant drug-drug interactions (CSDDIs) than older HIV drugs, a 1985-to-2019 systematic review did not turn up evidence that modern combinations lead to fewer CSDDIs [1]. University of Liverpool researchers who conducted this study suggested that lack of improvement may reflect today's older HIV populations with more comorbidities requiring more comedications.
Researchers from the University of Liverpool and other centers scoured 3 electronic databases-PubMed, Web of Science, and SCOPUS-for studies of CSDDI incidence in people taking antiretrovirals and comedications published between January 1987 and October 2020 [2]. They excluded studies of children, studies limited to specific antiretroviral combinations, and studies of people with specific comorbidities or coinfections. They eliminated duplicate citations of the same studies, then at least 2 independent reviewers screened citations for CSDDIs.
The researchers graded DDI severity by the Liverpool Drug Interaction protocol [3] or the nearest equivalent if the study used another drug-interaction screening tool. By the Liverpool system, red indicates drug interactions that are contraindicated or strongly not recommended; amber indicates interactions that necessitate a change in dosage or dose timing or increased monitoring; green indicates no interaction. For each study the 2 reviewers counted the number of people taking antiretrovirals and the number with at least one CSDDI (red or amber interaction), at least one red interaction, and at least one amber interaction.
Sifting through 20,601 DDI reports, the Liverpool team found 25 that reported total number of patients with a CSDDI between January 1985 and April 2019. Over that span, the CSDDI rate did not change significantly (Pearson correlation coefficient R(2) = 3.881 x 10(-5), P = 0.0764). Fourteen articles reported total numbers of patients who had either an amber DDI or a red DDI from January 2006 through December 2018. The rate of amber DDIs did not change over that period (R(2) = 0.01316, P = 0.6838); nor did the rate of red DDIs (R(2) = 0.1620, P = 0.1369).
Older median age correlated with the proportion of people who had at least 1 red drug-drug interaction (R(2) = 0.5212, P = 0.0053). But older age did not correlate with the proportion who had at least 1 amber drug-drug interaction.
The drug classes that interacted most with modern antiretrovirals were corticosteroids, multivitamins, acid-reducing agents, and central nervous system drugs.
Although modern antiretrovirals (especially integrase inhibitors and new nonnucleosides) are much less likely to cause CSDDIs than older antiretrovirals, the researchers concluded, the overall prevalence of CSDDIs has not dropped through more than 3 decades. An aging HIV population with accumulating comorbidities requiring multiple comedications, the authors speculated, "more than offsets any relative risk reduction in DDIs, ensuring that the absolute risk of DDIs remains significant, affecting a significant proportion of patients receiving antiretrovirals." The take-home message seems clear: Clinicians must continue checking for potential drug-drug interactions before prescribing an antiretroviral.
References
1. Hodge D, Hodel E, Hughes E, Hazenberg P, Khoo S. Prevalence of clinically significant drug-drug interactions with antiretrovirals against HIV over time: a systematic review of the literature. International Workshop on Clinical Pharmacology of HIV, Hepatitis and Other Antiviral Drugs 2021. September 20-22, 2021. Abstract 15.
2. PROSPERO registration CRD42020216066. Prevalence of clinically significant drug-drug interactions with antiretrovirals against HIV over time: a systematic review of the literature. https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=216066
3. University of Liverpool. HIV Drug Interactions.
https://www.hiv-druginteractions.org/checker
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