The Incidence and Severity of Drug Interactions Before and After Switching Antiretroviral Therapy to Bictegravir/Emtricitabine/Tenofovir Alafenamide in Treatment Experienced Patients

Simple, safe and effective antiretroviral therapy (ART) can provide optimal treatment outcomes for people living with HIV infection (PLWH) [1]. Increasingly complex and poorly tolerated regimens, on the other hand often limit ART adherence, while drug-drug interactions (DDIs) and safety concerns with individual ART agents can limit treatment selection [2-4]. Fortunately, recent advances in ART have included the emergence of several highly effective, safe and well tolerated regimens with limited DDIs. In clinical trials, integrase strand transfer inhibitors (INSTIs) such as raltegravir, elvitegravir, dolutegravir and bictegravir are consistently as effective or more effective than comparator agents and often superior in terms of tolerability [5-10]. Due to their efficacy, safety, and tolerability, INSTI-based regimens are now routinely used in treatment naïve patients and emerging data suggests that several may be used to simplify therapy for selected patients with treatment experience [11, 12].

Among the INSTIs, bictegravir is the newest agent in the class [13]. Similar to dolutegravir and raltegravir and in contrast to elvitegravir, it has few significant drug-drug interactions. Unlike dolutegravir and raltegravir, bictegravir is available as part of a single-tablet, once-daily regimen that includes tenofovir alafenamide and emtricitabine (BIC/TAF/FTC). Raltegravir is not available within a single tablet regimen, while dolutegravir is available as part of a single-tablet regimen, but it includes abacavir, which has been linked to an increased cardiovascular disease risk. As a result, BIC/TAF/FTC is currently among the most effective, safe, well-tolerated treatment options with limited drug-drug interactions.

With several new treatment options available, particularly in the INSTI class, current guidelines advocate switching ART when possible in virologically suppressed, ART experienced patients [1]. Switching ART can simplify treatment, improve tolerability, eliminate toxicity, and mitigate drug-drug interactions. When switching ART for any reason, it is critical to review a patient's full HIV treatment history, including virologic responses, past ART-associated toxicities, and cumulative resistance before selecting a new regimen [1].

Drug-drug interaction assessments with a patient's concomitant medications should also be performed prior to switching ART. More than 70% of the HIV population will be above the age of 50 by the year 2020 and many are receiving 5 or more medications for common chronic conditions in addition to being ART experienced [14, 15]. Cardiovascular disease, hepatic and renal disease, osteoporosis, insulin resistance, metabolic disorders, and cancers are among the conditions that can occur more commonly in PLWH and at times earlier in life in comparison to their HIV negative counterparts [16]. Drug-drug interactions between medications needed to treat or prevent these comorbid conditions can often interact with ART. Switching ART, in many circumstances can reduce the number drug interactions with medications for comorbid conditions. Conversely, switching can also lead to new interactions requiring intervention to avoid toxicities or prevent ineffective treatment.

Multiple studies have confirmed that switching HIV treatment can improve patient adherence and quality of life [17]. Several studies have also confirmed that clinically significant drug-drug interactions are common in patients living with HIV, but none have assessed changes in the incidence and severity of drug-drug interactions in the setting of ART switches [18-20]. The primary objective of this study is to assess changes in the incidence and severity of drug interactions before and after switching ART to BIC/TAF/FTC -based regimens in treatment experienced patients.