Potential drug–drug interactions in the era of integrase strand transfer inhibitors: a cross-sectional single-center study in Japan

Abstract

Background Potential drug–drug interactions (PDDIs) commonly occur because of aging and comorbidities in people living with human immunodeficiency virus (HIV; PLWH). Protease inhibitors and non-nucleoside reverse transcriptase inhibitors have been reported to cause PDDIs in these patients. However, there are few reports of PDDIs in the era of treatment using integrase strand transfer inhibitors. Therefore, we investigated PDDIs in Japanese PLWH receiving antiretroviral drugs (ARVs). Methods This was a cross-sectional observational study conducted in Japanese outpatients. All eligible patients who had received ARV therapy for at least 48 weeks were enrolled. The primary endpoint was the incidence of PDDIs detected using the Lexicomp® interface. Results Of the 71 eligible patients, 51 (71.8%) were prescribed concomitant non-ARV medications. In 21 patients (29.6%), PDDIs with the potential to reduce the effects of ARVs occurred, although the HIV load was suppressed in all cases. Polypharmacy (the use of ≥5 non-ARVs) was observed in 25 patients (35.2%). There was a significantly higher median number of non-ARV medications in the PDDI group than in the non-PDDI group (6 vs. 3, P < 0.001). Furthermore, the proportion of patients on polypharmacy was significantly higher in those with PDDIs than in those without PDDIs (81.0% vs. 26.7%, P < 0.001). Conclusions The incidence of PDDIs is relatively high in Japanese PLWH, even in the era of treatment using integrase strand transfer inhibitors. Therefore, it is important for patients and health care providers to be constantly aware of PDDIs associated with ARV treatment.

Prevalence of Potentially Clinically Significant Drug–Drug Interactions With Antiretrovirals Against HIV Over Three Decades: A Systematic Review of the Literature

“…These studies may therefore skew toward more clinically significant DDIs due to increased polypharmacy in older age groups. 17 One study selected patients aged 20 years or older because this was the age of majority in the location at the time 18 ; we assessed the risk of bias of this article as low because very few patients aged 18-20 years were recruited into other cohorts. One study included a very low number of pediatric patients (0.49% of the cohort), 19 this was well below our threshold of 5%, and therefore, we did not consider it to cause significant risk of bias.…”

“…22,23 However, another study by Kunimoto et al, found a prevalence of 62% clinically significant DDIs in a cohort with 89% integrase inhibitor use (of which 6% was coprescribed with a protease inhibitor). The most common interactions in this cohort were between integrase inhibitors and divalent cations, 18 an interaction that can easily managed by dose timing, and it is unclear whether the DDIs reported were managed.…”

“…Oreagba 2019 30 84.2 Chen 2020 20 3.0 Deutschmann 2020 23 22.5 1.7 El Moussaoui 2020 52 43.5 4.6 40. 8 4.6 Pontelo 2020 53 50.0 Ruellan 2020 15 25.1 20.1 7.1 Schlaeppi 2020 54 31.2 30.7 0.4 Funke 2021 55 41.5 1.3 Kunimoto 2021 18 62.0 Murray 2021 16 84. regimens. In addition, studies from Switzerland and the United Kingdom suggest that younger individuals (with more recent initiation of antiretroviral therapy) are more likely to be receiving first-line, integrase-containing fixed-dose formulations than older patients who were more likely to be optimally controlled on older antiviral regimens.…”

An overview of multimorbidity and polypharmacy in older people living with HIV

“…29 Factors associated with polypharmacy included number of comorbidities, clinic attendance and number of clinics participants had to attend. 27 Taking more than five drugs increases the risk of adverse drug events, [62][63][64] drug interactions, 60,65 medication errors, and poor compliance. Collectively, these can lead to delirium, frailty, falls and fractures, 66 cognitive impairment, 67 hospitalization, 68,69 and mortality.…”

“…Taking more than five drugs increases the risk of adverse drug events, 62–64 drug interactions, 60,65 medication errors, and poor compliance. Collectively, these can lead to delirium, frailty, falls and fractures, 66 cognitive impairment, 67 hospitalization, 68,69 and mortality 61 …”