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HomeJAIDS: Journal of Acquired Immune Deficiency Syndromesindex/list_12208_1Safety and Tolerability of Once Daily Coformulated Bictegravir, Emtricitabine, and Tenofovir Alafenamide...

Safety and Tolerability of Once Daily Coformulated Bictegravir, Emtricitabine, and Tenofovir Alafenamide for Postexposure Prophylaxis After Sexual Exposure

Abstract and Introduction

Abstract

Background: Antiretroviral post-exposure prophylaxis (PEP) is recommended to prevent HIV infection after a high-risk exposure, but current regimens have presented challenges in tolerability, regimen completion, and potential drug–drug interactions. Because coformulated bictegravir, emtricitabine, and tenofovir alafenamide [BIC/FTC/tenofovir alafenamide (TAF)] is effective for HIV treatment, it was evaluated for use for PEP.

Setting: Boston community health center.

Methods: Individuals accessing PEP were enrolled in an open-label study of coformulated BIC/FTC/TAF, taken as one pill daily for 28 days. Pearson’s χ 2 and Fisher’s exact tests were used to assess whether BIC/FTC/TAF differed with respect to side effects and regimen completion rates compared with historical PEP regimens.

Results: Between August, 2018 and March, 2020, 52 individuals enrolled in the study. Most identified as cisgender gay (67.3%) or bisexual (11.5%) men, but 7.7% identified as cisgender heterosexual men and 3.8% cisgender heterosexual women. The most common regimen side effects were nausea or vomiting (15.4%), fatigue (9.6%), and diarrhea/loose stools (7.7%), which were less common than historical controls using other PEP regimens, including those containing other integrase strand transfer inhibitors. Only 1 participant discontinued the regimen because of fatigue, and all other side effects were self-limited. Almost all participants (90.4%) completed the indicated regimen, which was a higher completion rate compared with earlier PEP regimens, and none became HIV-positive.

Conclusions: BIC/FTC/TAF coformulated as a single daily pill was found to be safe, well-tolerated, and highly acceptable when used for PEP, and compared more favorably than historical PEP regimens used at an urban health center.

Introduction

Although no human data are available from randomized controlled clinical trials that demonstrate the efficacy of antiretroviral postexposure prophylaxis (PEP) in preventing HIV infection, it has become an accepted modality for individuals who sustained a recent potential exposure to HIV for close to 2 decades.[1] The empirical support for this approach has been based on numerous simian retroviral challenge studies[2–4] and a retrospective case control study of HIV-exposed health care workers, whose risk for seroconversion was decreased by more than 80% if they used postexposure azidothymidine.[5] The demonstrated safety and efficacy of daily emtricitabine (FTC) and tenofovir-containing regimens for pre-exposure prophylaxis (PrEP) in approximately one million people has provided some additional corroborative support for the use of antiretroviral chemoprophylaxis.[6]

However, the incidence of PEP-associated adverse events related to the first approved regimens was over 60%, primarily because of the use of zidovudine and protease inhibitors.[7,8] Although most of these adverse effects were not intolerable, experience from both occupational and nonoccupational settings found that close to 1/2 of individuals for whom PEP was recommended failed to complete their prescribed regimen.[8,9] Drug–drug interactions with other medications created other complications.[10] The demonstration of the excellent efficacy and tolerability of integrase strand transfer inhibitors as a part of a highly active antiretroviral therapy regimen has created new opportunities to create simpler and better tolerated PEP regimens. Prior studies found that raltegravir given twice a day in conjunction with once daily coformulated tenofovir disoproxil fumarate (TDF) and FTC was safe, and well-tolerated, but some participants did not complete the regimen as prescribed, often because of not adhering to the twice daily use of raltegravir.[11] A subsequent study of the single pill coformulation of elvitegravir, cobicistat, FTC, and TDF used for PEP was also well-tolerated and associated with good adherence, but concerns about potential drug–drug interactions with cobicistat persist.[12] Based on these earlier studies, there was evidence that a well-tolerated single daily pill regimen that did not have major drug–drug interactions may be a particularly desirable regimen for anti-HIV PEP.

The fixed drug combination of bictegravir, FTC, and tenofovir alafenamide (BIC/FTC/TAF) could be an optimal new regimen for PEP, because it has been shown to be potent and well-tolerated when used for HIV treatment, without common drug–drug interactions.[13–15] A simian retroviral challenge study found that animals who received one dose of BIC/FTC/TAF before and after exposure to simian immunodeficiency virus were highly protected from infection.[16] In a phase 1 trial, 20 participants took part in a 10-day monotherapy study comparing BIC to placebo with 4 participants assigned to one of four dosage groups (5 mg, 25 mg, 50 mg, and 100 mg) and 5 participants assigned to a placebo.[17] Participants in all 4 study arms experienced rapid and sustained declines in HIV plasma RNA. The drug was well-tolerated with no participants discontinuing the study product because of adverse events. Subsequent later phase trials confirmed earlier data, demonstrating clinical efficacy and tolerability, with the most common adverse events being headache (8%), nausea (8%), and diarrhea (12%) with no discontinuation of the regimen from these events.[13–15] These studies also showed TAF/FTC and BIC to have a favorable pharmacokinetic profile, supportive of once-a-day dosing with a high barrier to resistance.[18]

Given the favorable data regarding the pharmacokinetics, safety and tolerability of daily BIC/FTC/TAF, the authors initiated a Phase IV study of this single-pill daily regimen for PEP. The Boston community health center where the trial was conducted has maintained the largest PEP program in New England for more than 20 years,[19] and has been actively investigating new, potent, and better tolerated regimens for PEP since then.[11,12,20]

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