SYMPOSIUM 9: Is there a role of TDM for long-acting formulations?
Tracks
Track 1
Tuesday, September 23, 2025 |
10:30 AM - 12:00 PM |
Grand Copthorne Waterfront Hotel - Grand Ballroom I |
Details
Long-acting injectable formulations are now a reality as maintenance therapy for many diseases, including infectious diseases. Today we have LAI antibiotics for the chronic therapy of osteoarticular infections, LAI antiretrovirals for the treatment of people with HIV and, more recently also LAI formulations of echinocandins for the treatment of fungal infections. These drugs are often given at fixed intervals, despite preliminary evidence of considerable pharmacokinetic variability. This symposium will address the possible role of TDM as a tool to personalise the frequency of administration of long-acting anti-infectious drugs. It is also thought to introduce a reading on the applications of TDM for long-acting formulations of antipsychotics, as an example to be followed in the field of infectious diseases.
Speaker
A/Prof Georgios Schoretsanitis
Zucker Hillside Hospital
TDM of LAI antipsychotics: an example to follow for LAI anti-infectives?
Abstract
Long-acting injectable (LAI) formulations of second-generation antipsychotics (SGA) are emerging as a mainstay in the treatment of schizophrenia-spectrum patients, as their use essentially improves adherence and contributes to reduced relapse risk. We provide pharmacokinetic considerations as a cornerstone of a smooth transition from oral to LAI SGAs based on works previously identified in a systematic manner. Quantifying antipsychotic exposure during baseline oral SGA-treatment based on the patient's SGA blood (plasma or serum) levels may often provide a more appropriate orientation method when selecting the equivalent LAI dose over dose selection based on population-based data. Specifically, oral dose adjustment during LAI transition can be guided by regularly assessing SGA levels right before the next LAI injection.
While LAI SGAs increasingly dominate the maintenance treatment of schizophrenia-spectrum disorders, the development of novel formulations with longer injection intervals is expected to provide increased administration ease. Nevertheless, transitioning from oral SGA to LAIs remains a challenge in clinical routine. Personalizing LAI-based treatment involves tailoring the transition from oral to LAIs taking the individual and drug-related pharmacokinetic peculiarities into consideration.
While LAI SGAs increasingly dominate the maintenance treatment of schizophrenia-spectrum disorders, the development of novel formulations with longer injection intervals is expected to provide increased administration ease. Nevertheless, transitioning from oral SGA to LAIs remains a challenge in clinical routine. Personalizing LAI-based treatment involves tailoring the transition from oral to LAIs taking the individual and drug-related pharmacokinetic peculiarities into consideration.
Biography
I am a psychiatrist and the head of the outpatient unit of the Department of Psychiatry, Psychotherapy and Psychosomatics, Hospital of Psychiatry, University of Zurich, Zurich, Switzerland, whereas I also am appointed associate Professor in the Barbara Zucker School of Medicine at Northwell/Hofstra, Hempstead, NY, USA. Over the past decade I have been working on big therapeutic drug monitoring (TDM) datasets for different neuropsychotropic agents including clozapine. I am member and vice-president of the task force for TDM of the German Collegium of Neuropsychopharmacology (AGNP), which regularly publishes updates of consensus works for TDM in Neuropsychopharmacotherapy.
Prof Natella Y. Rakhmanina
The George Washington University
Long Acting treatment of anti-infectives in paediatrics
Abstract
Dr. Rakhmanina will review the current developments in the long-acting formulations of anti-infective drugs for pediatric populations. The session will focus on the current pipeline in the development of the novel antiviral, antibacterial and antiparasitic agents to treat most common pediatric health conditions globally such as HIV infection, tuberculosis, bacterial pneumonia, osteomyelitis, malaria, and other infections. The audience will learn about specific challenges in the developmental pharmacology that affect the formulations and dosing considerations of the long-acting anti-infective formulations for infants and children.
Biography
Dr. Natella Rakhmanina is a Professor of Pediatrics at George Washington University and serves as an Associate Chief of the Division of the Pediatric Infectious Diseases and a Director of the HIV Prevention and Treatment Services at Children’s National Hospital in Washington, DC, USA. Dr. Rakhmanina obtained her MD degree at People’s Friendship University in Moscow, Russia, and her PhD degree in clinical pharmacology at the Erasmus University in Rotterdam, the Netherlands. For more than 25 years she has been providing care for infants, children and adolescents affected by the HIV epidemic. She is a successful clinical researcher, focusing her studies on the treatment and prevention of HIV in children and adolescents and serving as a principal investigator of NIH, CDC and industry funded pediatric and adolescent HIV studies.
Dr. Rakhmanina has held multiple regional, national, and international professional roles including serving as immediate past Chair of the Committee on Pediatric AIDS at the American Academy of Pediatrics. For over a decade, she has been serving and continues to serve as a member of the US Department of Health and Human Services Panel on the Pediatric Antiretroviral Therapy and Management Guidelines at the Office of AIDS Research Advisory Council in National Institutes of Health and the Pediatric Advisory Working Group at the World Health Organization. She also has more than a decade experience in global health serving as a Senior Technical Advisor at Elizabeth Glaser Pediatrics AIDS Foundation where she led diverse projects on pediatric and adolescent HIV treatment in Sub-Saharan African countries.
Dr Paul Thoueille
Lausanne University Hospital
PopPK Modelling and TDM for Individualized Dosing of Long-Acting Antiretrovirals
Abstract
Long-acting injectable antiretroviral drugs are a paradigm shift in the treatment and prevention of HIV infection by eliminating the need of daily medication. However, real-world data have revealed substantial pharmacokinetic (PK) variability, challenging the one-size-fits-all dosing approach.
Key factors affecting long-acting antiretrovirals exposure after intramuscular administration were identified, including bodyweight, sex, as well as significant intra- and inter-individual variability in absorption and elimination. In particular, model-based simulations highlighted sex-related differences in cabotegravir PK: females had lower trough concentrations at treatment initiation but significantly higher levels during the late maintenance phase. These findings have direct clinical implications, particularly for individuals with additional risk factors – such as obesity – who may benefit from individualized TDM where feasible.
This presentation will explore how population pharmacokinetic (popPK) modelling and TDM can refine dosing strategies for long-acting antiretrovirals by tailoring dosing intervals based on individual PK data. It will discuss the integration of popPK models and Bayesian approaches into routine clinical practice, aiming to optimize drug exposure, minimize the risk of under-exposure, and sustain virologic suppression while reducing treatment burden.
Key factors affecting long-acting antiretrovirals exposure after intramuscular administration were identified, including bodyweight, sex, as well as significant intra- and inter-individual variability in absorption and elimination. In particular, model-based simulations highlighted sex-related differences in cabotegravir PK: females had lower trough concentrations at treatment initiation but significantly higher levels during the late maintenance phase. These findings have direct clinical implications, particularly for individuals with additional risk factors – such as obesity – who may benefit from individualized TDM where feasible.
This presentation will explore how population pharmacokinetic (popPK) modelling and TDM can refine dosing strategies for long-acting antiretrovirals by tailoring dosing intervals based on individual PK data. It will discuss the integration of popPK models and Bayesian approaches into routine clinical practice, aiming to optimize drug exposure, minimize the risk of under-exposure, and sustain virologic suppression while reducing treatment burden.
Biography
Dr. Paul Thoueille is a clinical pharmacometrician and hospital pharmacist who completed his PhD in 2024. His main focus is the development of Therapeutic Drug Monitoring (TDM) as a tool for individualized dosage adjustment of drugs. He is an expert in population pharmacokinetic modelling, which he applied notably for the analysis of long-acting intramuscular antiretrovirals. He currently leads the TDM Unit at the Service of Clinical Pharmacology of the University Hospital of Lausanne, Switzerland.
A/Prof Ethel Weld
Johns Hopkins University School of Medicine
LAI formulations of anti-infectives in adults
Abstract
This session will cover the state of the field of existing approved long-acting anti-infectives, with a primary focus on HIV therapeutics. The clinical trial evidence for efficacy and safety, the influence of long-acting drug exposures on efficacy and toxicity, ideal use cases, and the factors contributing to PK variability between occasions and between individuals will all be discussed. Selected case scenarios of clinical virological failures while receiving long-acting antiretrovirals will be presented and discussed, as well as potential strategies to mitigate these. The talk will also touch on long-acting anti-infective therapeutics in the late pipeline, including oral formulations dosed less frequently than daily, and on formulations in development that hold high promise as long-acting strategies.
Biography
Dr. Ethel D. Weld, MD, PhD is an assistant professor of medicine, pharmacology, and molecular sciences at the Johns Hopkins University School of Medicine. She earned her medical degree from the University of Chicago and her PhD in Clinical Investigation from the Johns Hopkins Bloomberg School of Public Health. She is board certified in Internal Medicine and Pediatrics and subspecialty board certified in Infectious Diseases and Clinical Pharmacology, and serves as an attending Infectious Diseases physician at the Johns Hopkins Hospital and the Johns Hopkins Bayview Medical Center. She is the recipient of Johns Hopkins Center for AIDS Research (CFAR) faculty retention funding, a CFAR Faculty Development Award for her study “Feasibility, Development and Validation of a Non‐cold‐chain‐requiring Assay to Measure Long‐acting Antiretrovirals in Blood”, and an NIH K23 mentored career award for her project entitled “Optimizing the Use of Long-Acting Antiretrovirals for Youth with HIV”. She chairs the IMPAACT 2005 and 2034 trials, both multi-site international studies of novel TB therapeutics in children. Her primary research focus is on developing HIV and TB therapeutics in special populations, and optimizing long-acting therapeutics for individuals with HIV and adherence challenges.
Session chair
Dario Cattaneo
Department of Biomedical Sciences Hunimed University, Pieve Emanuele
Natella Y. Rakhmanina
The George Washington University
