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Antiretroviral therapy (ART) is highly effective for the treatment of HIV-1 infection. ART previously consisted of concomitant administration of many drugs, multiple times per day. Currently, ART generally consists of two- or three-drug regimens once daily as fixed-dose combinations. Drug monitoring may be necessary to ensure adequate concentrations are achieved in the plasma over the dosing interval and prevent further HIV resistance formation. Additionally, nonadherence remains an issue, highlighting the need to ensure sufficient ART exposure. Towards this effort, we developed and validated a highly selective ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the simultaneous quantification of a panel of nine antiretrovirals: abacavir, bictegravir, cabotegravir, dolutegravir, doravirine, emtricitabine, lamivudine, raltegravir, and tenofovir in human plasma. Using only 50 µL of plasma, a simple protein precipitation with acetonitrile with internal standards followed by reconstitution in 50 uL (high) or 400 uL (low) was performed. Analyte separation was achieved using a multistep UPLC gradient mixture of (A: 0.1% formic acid in water and B: acetonitrile) and a Waters CORTECS T3 (2.1 ×100 mm) column. The method was comprehensively validated according to the United States Food and Drug Administration Bioanalytical Guidelines over two clinically relevant ranges (1–250 ng/mL and 100–5000 ng/mL) with excellent linearity (R2 > 0.99 for all). The assay run time was 7.5 min. This method achieves acceptable performance of trueness (89.7–104.1%), repeatability, and precision (CV <15%), and allows for simultaneous quantification of guideline-recommended ART regimens. This method can be utilized for the therapeutic monitoring of antiretrovirals in human plasma. [Display omitted] • Recommended antiretroviral therapy consists of multiple therapeutic agents. • Nonadherence remains a concern in those living with HIV. • Quantifying concentrations in plasma ensures adequate antiretroviral exposure. • A UPLC-MS/MS method was validated to quantify nine antiretrovirals in human plasma. [ABSTRACT FROM AUTHOR]

The mainstay of antiretroviral therapy (ART) has been combination oral therapy. While oral ART is highly effective, nonadherence remains a chief concern. Addressing this concern in recent years is the emergence of long-acting antiretrovirals for the treatment and prevention of HIV-1 infection. The most recently approved long-acting antiretroviral is the first-in-class capsid inhibitor lenacapavir (LEN) for heavily treatment-experienced adults with multidrug-resistant HIV-1 infection. Due to its biannual subcutaneous dosing scheme to inhibit the HIV-1 capsid, LEN exhibits unique pharmacokinetics and reinforces an evolving era of ART. In this review, we evaluate published and accepted research articles, conference proceedings, and clinical trial records to provide a comprehensive overview of LEN for treatment and preliminary data for the prevention of HIV-1 infection. These data include clinical trials outcomes, in vitro and in vivo resistance profiles, and preclinical data supporting downstream indications. We also discuss the unique clinical pharmacology of LEN with the goal of serving as a resource toward subsequent physiologically based, population-based, and other miscellaneous pharmacometric-focused analyses. Given the dynamic nature of the HIV treatment and prevention research fields, we also discuss ongoing studies related to LEN for treatment-naïve adults and for prevention. Lastly, we discuss important pharmacologic gaps in special populations, drug-drug interactions, and at the sites of action germane to HIV treatment and prevention. The information discussed in this review will provide knowledge and understanding of the unique pharmacologic properties of LEN to assist clinicians and researchers as they navigate the dynamic HIV research landscape., (© 2024 The Author(s). Clinical Pharmacology & Therapeutics © 2024 American Society for Clinical Pharmacology and Therapeutics.)

Accrediting bodies for Doctor of Pharmacy (Pharm.D.) and postgraduate residency training programs recognize the importance of research and scholarship training. However, specific guidance on how research and scholarship fundamentals should be delivered to trainees have not been provided. As a result, competing priorities often create barriers for trainees to develop research and scholarship skills and limit the trainees' ability to conduct and participate in high-quality, meaningful research experiences. The purpose of this "how-to" guide is to assist pharmacy school faculty and pharmacy residency program directors with strategies to overcome programmatic, trainee, and project barriers to providing a high-quality training experience in research and scholarship. Programmatic topics addressed include institutional support and program oversight, expertise and number of research mentors, incentives for mentor engagement, and competing priorities that diminish time for research activities. Trainee topics include lack of trainee interest in the assigned project, trainee departure prior to project completion, lack of knowledge of the publication process, and time constraints to work on the project. Project topics addressed include time needed to initiate a project, training on methodology relevant to a project, selection of projects that lack rigor, depth, or feasibility, and resource constraints to disseminate project results. A summary of specific recommended actions is provided to effectively overcome these common barriers encountered in research and scholarship training programs., Competing Interests: The authors have no financial disclosures or conflicts of interest to declare.