lopinavir/ritonavir/tenofovir (TLC-ART 101) / National Institute of Allergy and Infectious Diseases, University of Washington - LARVOL DELTA

Persistent and long-acting intracellular three HIV drug concentrations in participants after subcutaneous TLC-ART 101 (IAS-HIV 2025) - "Injectable TLC-ART101, a Drug-combination NanoParticle (DcNP) platform with lopinavir, ritonavir, and tenofovir, targets lymphoid tissues during first-pass distribution... Current oral or injectable ART exhibits PBMC-to-plasma ratios below 1. TLC-ART101, using a DcNP platform, achieved higher intracellular than plasma drug levels. This study provides evidence that a cell-targeted, long-acting product can enhance intracellular concentrations."

Human Immunodeficiency Virus • Infectious Disease

Long-acting Injectable Containing Lopinavir Eliminates Reliance on Ritonavir Pharmacokinetic Enhancement. (PubMed, J Infect Dis) - "However, in the long-acting subcutaneous injectable dosage form TLC-ART 101, lopinavir persisted in plasma for 57 days, while ritonavir was detectable for only 3-7 days. The remarkable duration of lopinavir suggests that ritonavir may be unnecessary in long-acting injectable products, potentially reducing side effects and drug-drug interactions."

Journal • PK/PD data • Human Immunodeficiency Virus • Infectious Disease • Novel Coronavirus Disease

First-in-Human Study of a Long-Acting Injectable 3 Antiretroviral Drug Combination Nanoparticle (CROI 2025) - "The TLC-ART program, a public-private partnership, engineered a novel 3-drug combination nanoparticle (DcNP) for subcutaneous injection containing lopinavir (LPV), ritonavir (RTV), and tenofovir (TVF) "TLC-ART 101" bound with DSPC and mPEG-DSPE lipid excipients...A HIGH Dose participant experienced anaphylaxis 6hrs after dosing, recovering after intervention including epinephrine...Systemic hypersensitivity was not Type I (non-IgE) and is under mechanistic exploration. This FIH trial will support development of complete subcutaneously administered LA-ART regimens, including TLC-ART 301 [dolutegravir/lamivudine/TFV (LA-TLD)], currently in pre-clinical studies."

P1 data • Dermatology • Gastrointestinal Disorder • Human Immunodeficiency Virus • Immunology • Infectious Disease • Pruritus

First in Human Study of TLC-ART 101 (ACTU 2001) (clinicaltrials.gov) - P1 | N=12 | Completed | Sponsor: University of Washington | Recruiting ➔ Completed | Trial completion date: Dec 2025 ➔ Jun 2024 | Trial primary completion date: Oct 2025 ➔ Jun 2024

Trial completion • Trial completion date • Trial primary completion date • Human Immunodeficiency Virus • Infectious Disease

A first-in-human phase 1 study of the novel nanoparticle-formulated TLC-ART 101, a single subcutaneous injection containing 3 HIV drugs, demonstrates long-acting pharmacokinetics and initial clinical safety (AIDS 2024) - "The only current complete LAI regimen, LA- cabotegravir + LA-rilpivirine faces barriers to global implementation due to drug resistance, cost, distribution challenges, and clinic-required injections. The TLC-ART program has developed TLC-ART-101 composed of 3 HIV drugs - lopinavir(LPV), ritonavir(RTV), and tenofovir(TFV) - combined in drug combination nanoparticles (DcNP) and given subcutaneously... With a fraction of daily LPV/RTV/TFV oral dosing, the three HIV-drug TLC-ART-101, enabled by DcNP technology, appeared safe and well-tolerated. In contrast to the short half-life of each drug when given orally, TLC-ART 101 demonstrated a 38-fold, 2-fold, and 11-fold half-life extension for LPV/RTV/TFV respectively in people versus oral dosing. Cohort 2 is in process with a dose escalation to 2.7-fold the initial dose and a longer study duration."

Clinical • P1 data • PK/PD data • Gastrointestinal Disorder • Human Immunodeficiency Virus • Infectious Disease • Pruritus

A novel physiologically-based pharmacokinetic (PBPK) model to guide pediatric dosing for a long-acting triple-drug-in-one injectable product candidate TLC-ART-101 (lopinavir/tenofovir/ritonavir) (AIDS 2024) - "Pediatric TLC-ART-101 dose to provide equivalent AUC by PBPK modeling.Age-weight bandlopinavir ritonavir tenofovir Adults16 mg4.1 mg9.2 mgBWPBPKBWPBPKBWPBPK10-18y, or>30kg9.0 mg10 mg2.0 mg2.0 mg4.2 mg4.5 mg6-14y, or 20-30kg7.0 mg4.1 mg1.9 mg1.7 mg3.5 mg3.8 mg3-6y, or 14-20kg5.0 mg3.5 mg3.0 mg2.5 mg3.0 mg2.0 mg1-3 y, or 10-14kg3.0 mg0.65 mg2.0 mg0.65 mg1.8 mg0.8 mgBW: body-weight dose proposals (allometry); PBPK: physiologically based PK dose projection. Integrating ontogeny and developmental changes in metabolic and physiological parameters, we developed a range of entry doses for equivalent exposure to TLC-ART-101 in children. The PBPK approach may serve as a starting point for advancing pediatric treatment studies to mitigate risks as we advance long-acting products for children living with HIV worldwide."

Clinical • PK/PD data • Human Immunodeficiency Virus • Infectious Disease • Pediatrics

"Make it convenient for us": design and delivery preferences for a targeted long-acting drug-combination injectable treatment for children and youth with HIV in Kenya (AIDS 2024) - "LAI-cART products for children and adolescents should address self-injection fears and accessibility barriers, and include consideration of health system processes and constraints."

Clinical • Fatigue • Human Immunodeficiency Virus • Infectious Disease • Novel Coronavirus Disease • Pain • Pediatrics

Pediatric PBPK Scaling Model for a New Long-Acting, 3 HIV Drug Combination in a Single Injection (CROI 2024) - "Background: The TLC-ART program successfully engineered lopinavir (LPV), ritonavir (RTV), and tenofovir (TFV) in a single 3-drug long-acting (LA) injectable suspension (TLC-ART 101) that has undergone scale-up, stability and preclinical safety studies...We developed a novel PBPK modeling approach that accounts for anatomical, physiological and enzymatic differences between species and age bands, including DDI assessments due to LPV- RTV. This integrated PBPK model may inform dose selection for clinical evaluation of long-acting HIV drug combinations such as TLC-ART 101, thereby accelerating pediatric access to long- acting treatments. To our knowledge, this drug-combination PBPK model is the first to demonstrate adaptability for multiple drugs as synchronized injections, integrating age-specific physiologic parameters."

Clinical • Human Immunodeficiency Virus • Infectious Disease • Pediatrics