Lenacapavir 463.5mg/1.5ml solution for injection vials

Abstract Purpose of Review By the end of 2023, approximately 39.9 million people worldwide were living with HIV, including 1.2 million in the United States. Although treatment advancements have improved health outcomes, HIV continues to pose significant challenges, particularly among key populations like men who have sex with men (MSM), transgender women, and cisgender women. Pre-exposure prophylaxis (PrEP) has emerged as an effective strategy to lower the risk of HIV transmission, but daily oral regimens often face adherence difficulties. This narrative review aims to summarize the effectiveness and safety of Lenacapavir, the latest long-acting injectable PrEP currently under clinical trials. Recent Findings Lenacapavir, a novel long-acting injectable PrEP with bi-annual dosing, offers significant advantages in terms of adherence and privacy, potentially reducing the stigma associated with daily medication. This review summarizes the effectiveness in preventing HIV, safety profile and the strategies being explored to overcome barriers to access. Compared to traditional daily oral PrEP options, lenacapavir has shown remarkable efficacy in recent clinical trials, including two different Phase 3 studies where it achieved a 100% prevention rate in cisgender women and a 96% prevention rate in cisgender men who have sex with men, transgender men, transgender women and gender non-binary individuals. Summary Lenacapavir holds promise as a transformative option in HIV prevention. However, continued research and development of strategies to improve access are essential to meet public health objectives and ultimately end the HIV epidemic by 2030.

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) is a long-acting capsid inhibitor of human immunodeficiency virus type 1 (HIV-1) being developed by Gilead Sciences Inc. It is available as an oral tablet and injectable solution, with the latter being a slow-release formulation to allow bi-annual subcutaneous administration. In August 2022, lenacapavir received its first approval in the EU for use in combination with other antiretroviral(s) in adults with multi-drug resistant HIV infection, for whom it is otherwise not possible to construct a suppressive anti-viral regimen. This article summarizes the milestones in the development of lenacapavir leading to this first approval for the treatment of HIV-1 infection.

Abstract licence: CC BY

Background: Injectable cabotegravir (CAB)/rilpivirine (RPV) is the only combination long-acting (LA) antiretroviral regimen approved for HIV. RPV may not be effective among individuals with non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance, which has >10% prevalence in many countries. Lenacapavir (LEN) is an LA capsid inhibitor given every 6 months, but has not been studied in combination with other LA agents. Methods: We assembled a case series from 4 US academic medical centers where patients with adherence challenges were prescribed LEN subcutaneously every 26 weeks/CAB (+/- RPV) intramuscularly every 4 or 8 weeks. Descriptive statistics, including viral load (VL) outcomes, were summarized. Results: All patients (n = 34: 76% male; 24% cis/trans female; 41% Black; 38% Latino/a; median age [range], 47 [28-75] years; 29% and 71% on CAB every 4 or 8 weeks) reported challenges adhering to oral ART. The reasons for using LEN/CAB with or without RPV were documented or suspected NNRTI mutations (n = 21, 59%), integrase mutations (n = 5, 15%), high VL (n = 6, 18%), or continued viremia on CAB/RPV alone (n = 4, 12%). Injection site reactions on LA LEN were reported in 44% (32% grade I, 12% grade 2). All patients but 2 (32/34; 94%) were suppressed (VL <75 copies/mL) after starting LEN at a median (range) of 8 (4-16) weeks, with 16/34 (47%) suppressed at baseline. Conclusions: In this case series of 34 patients on LEN/CAB, high rates of virologic suppression (94%) were observed. Reasons for using LEN/CAB included adherence challenges and underlying resistance, mostly to NNRTIs. These data support a clinical trial of LEN/CAB among persons with NNRTI resistance.

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