This workshop took place Friday, March 5, 2021. This was a virtual experience and these are the recordings of the lectures that took place during this Zoom virtual workshop..
LA/ER Implantable Therapy
Rajoli RKR, Demkovich ZR, Flexner C, Owen A, Siccardi M. Predicting pharmacokinetics of a tenofovir alafenamide subcutaneous implant using PBPK modelling. Antimicrob Agents Chemother. 2020 May 18:AAC.00155-20. doi: 10.1128/AAC.00155-20. PMID: 32423957.
Long-acting (LA) administration using a subcutaneous (SC) implant presents opportunities to simplify administration of antiretroviral drugs, improve pharmacological (PK) profile and overcome sub-optimal adherence associated with daily oral formulations. Tenofovir alafenamide (TAF) is a highly potent nucleoside reverse transcriptase inhibitor (NRTI) and an attractive agent for LA delivery, with a high potency and long intracellular half-life. The aim of this study was to predict minimum TAF doses required to achieve concentrations effective for HIV pre-exposure prophylaxis (PrEP). Daily drug-release requirements were then ascertained by averaging across the dosing interval.
Weld ED, Flexner C. Long-acting implants to treat and prevent HIV infection. Curr Opin HIV AIDS. 2020 Jan;15(1):33-41. doi: 10.1097/COH.0000000000000591. PMID: 31764198; PMCID: PMC7050620.
Subcutaneous implants are a promising technology to enable long-acting parenteral delivery of antiretroviral drugs (ARV) because they may be able to provide protective drugs concentrations for a year or longer following a single implant. The present review covers the current status of preclinical and clinical development of antiretroviral implants.
Rael CT, Martinez M, Giguere R, Bockting W, MacCrate C, Mellmen W, Valente P, Greene GJ, Sherman SG, Footer, KHA, D’Aquila RT, Carballo-Dieguez A, Hope TJ. Transgender Women's Concerns and Preferences on Potential Future Long-Acting Biomedical HIV Prevention Strategies: The Case of Injections and Implanted Medication Delivery Devices (IMDDs). AIDS Behav. 2020 May;24(5):1452-1462. doi: 10.1007/s10461-019-02703-5. PMID: 31654172; PMCID: PMC7181384.
There are several long-acting biomedical HIV prevention products in the development pipeline, including injections and implanted medication delivery devices (IMDDs). It is critical to understand concerns and preferences on the use of these products in populations that shoulder a disproportionate burden of the HIV epidemic, such as transgender women. This will allow researchers and public health professionals to construct interventions tailored to the needs of these women to promote optimal use of these tools. In studies of other biomedical HIV prevention products (e.g., oral PrEP) it is clear that transgender women have unique concerns related to the use of these strategies.
The purpose of this Funding Opportunity Announcement (FOA) is to stimulate the development of new and innovative sustained/extended release (SER) drug delivery systems (DDS) that can achieve extended durations (months to years) and provide systemic protection from all routes of HIV infection/transmission in at-risk individuals.
Application Deadline: December 4, 2019, by 5:00 PM local time of applicant organization
Sampson MR, Troy SB, Belew Y, Arya V, Struble KA. Considerations and challenges in developing novel long-acting antiretrovirals modalities for treatment and prevention of HIV-1 infection: a regulatory perspective. Curr Opin HIV AIDS. 2019 Sep 3. doi: 10.1097/COH.0000000000000587. [Epub ahead of print]. PMID: 31483323.
Outline some regulatory considerations and scientific challenges related to the development of long-acting antiretrovirals (ARVs) for the treatment and prevention of HIV-1 infection.
The annual Conference on Retroviruses and Opportunistic Infections (CROI) brings together top basic, translational, and clinical researchers from around the world to share the latest studies, important developments, and best research methods in the ongoing battle against HIV/AIDS and related infectious diseases. CROI 2021 will convene March 6 to March 10, 2021.
Montgomery ET, Atujuna M, Krogstad E, et al. The Invisible Product: Preferences for Sustained-Release, Long-Acting Pre-exposure Prophylaxis to HIV Among South African Youth. J Acquir Immune Defic Syndr. 2019 Apr 15;80(5):542-550. doi: 10.1097/QAI.0000000000001960. PMID: 30865050; PMCID: PMC6426447.
Long-acting injectable and implantable approaches aim to overcome some of the documented challenges with uptake and adherence to current HIV prevention methods. Youth are a key end-user population for these methods. We used qualitative methods to examine product attributes and preferences for current and future long-acting HIV prevention approaches.
Kovarova M, Benhabbour SR, Massud I, et al. Ultra-long-acting removable drug delivery system for HIV treatment and prevention. Nat Commun. 2018;9(1):4156. Published 2018 Oct 8. doi:10.1038/s41467-018-06490-w. PMID: 30297889; PMCID: PMC6175887.
Non-adherence to medication is an important health care problem, especially in the treatment of chronic conditions. Injectable long-acting (LA) formulations of antiretrovirals (ARVs) represent a viable alternative to improve adherence to HIV/AIDS treatment and prevention. However, the LA-ARV formulations currently in clinical trials cannot be removed after administration even if adverse events occur. Here we show an ultra-LA removable system that delivers drug for up to 9 months and can be safely removed to stop drug delivery.
Safe and efficacious medicines are available for the prevention and treatment of major diseases, but their effectiveness can be compromised by poor treatment completion. Lack of adherence can worsen clinical outcomes, leading to increased mortality, persistent transmission and increased drug resistance in the case of antimicrobials and antivirals. Analyses of treatment and prevention of HIV, malaria, and TB within public health programs show wide disparities in rates of completion, especially among specific populations and regions.
Application Deadline: 23 April 2019