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Objective: The objective of this review is to compare ibalizumab, fostemsavir, and lenacapavir, present the clinical trials evaluating each agent, and provide guidance on their use in highly-treatment experienced (HTE) population living with HIV (PWH). Data sources: A search of PubMed and clinicaltrials.gov was conducted using the search terms: ibalizumab, fostemsavir, and lenacapavir. Study selection and data extraction: English-language, clinical publications were included. Data synthesis: Ibalizumab, fostemsavir, and lenacapavir, are each first-in-class agents, that have major differences in mechanism of action, route and frequency of administration, pharmacokinetic parameters, including elimination half-life, potential for drug-drug interactions, safety profiles, and cost. Each has been shown, when combined with an optimized background regimen (OBR) with at least one other active agent, to achieve virologic suppression in HTE-PWH. Conclusion: In HTE-patients, adding ibalizumab, fostemsavir, and/or lenacapavir to at least one other active agent can lead to virologic suppression in this difficult to treat population. Monotherapy with any of these agents is not recommended and will lead to a high likelihood of drug resistance. Selection of which agent(s) to include with an OBR will depend on other patient factors including concomitant medications, acceptance of formulations (oral vs. subcutaneous vs. intravenous infusion), and potential access (both insurance-based and transportation). Adherence to all agents in the regimen is paramount to successful outcomes., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

HIV affects an estimated 1.2 million individuals in the United States and is disproportionately concentrated among African Americans, Latinos, and people of multiple races. Post-exposure prophylaxis (PEP) substantially decreases HIV transmission when started within 72 h after exposure, but problems of accessibility have hindered its widespread usage in communities at risk for HIV infection. Pharmacy-initiated PEP access was first permitted in New York City in 2017, allowing pharmacists to provide a 7-day supply of PEP without a prescription for consumers at high risk for HIV infection. It was expected that the broad reach and accessibility of community pharmacies would increase timely access to PEP for all individuals, especially those who already face significant barriers to accessing the healthcare system. Since then, eleven other states have followed suit and expanded the scope of outpatient pharmacy practice in order to increase the availability of HIV PEP but prescribing laws in over 75% of the US have not been changed. Much of the existing literature on HIV prevention focuses on PrEP access barriers with limited information on PEP access in the US. In this paper, we review the current status of pharmacist-initiated PEP in the US as part of the End the HIV Epidemic (EHE) initiative., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)