Table 1.

Selected Accomplishments of the LEAP Modelling and Simulation Core Service

Drug(s)	Disease	Key Findings	Reference
Cabotegravir, rilpivirine	HIV	• Optimal dose prediction of LAI cabotegravir and rilpivirine in children/adolescents aged 3–18 y. • Loading dose and maintenance dose prediction of cabotegravir ranged from 200 to 600 mg and from 100 to 250 mg, respectively, and for rilpivirine it ranged from 250 to 550 mg and from 150 to 500 mg, respectively, across various weight groups of children ranging from 15 to 70 kg.	[14]
Cabotegravir, rilpivirine	HIV	• Optimal dose and release rate has been determined for administration of cabotegravir and rilpivirine via a microarray patch. • Based on the simulations, patch sizes less than 60 cm2 should be viable for LA delivery. • These simulations underpinned a successful grant application to the UK engineering and physical sciences research council (EPSRC) and microarray development at Queens University Belfast. • The modelling approach has been further applied for the design of multipurpose prevention technology supporting the coadministration of ARVs and contraceptives.	[17]
Tenofovir alafenamide	HIV	• The feasibility of a TAF subcutaneous implant providing plasma concentrations for up to 6 mo was assessed. • Plasma, intracellular, and tissue tenofovir triphosphate concentrations were simulated to capture the preventive potential. Release rates above 1.4 mg/d were identified as optimal and are being used to inform implant development at RTI.	[24]
Rifampicin, cabotegravir, rilpivirine	TB/HIV	• Dramatic reduction in exposure of cabotegravir and rilpivirine was predicted when administered with rifampicin. • Half-lives predicted to remain unchanged resulting in several weeks of suboptimal exposure. • Preliminary recommendation that co-administration should be avoided.	[19]
Bedaquiline, delamanid, isoniazid, rifapentine	TB	• Optimal release rates to achieve monthly therapeutic exposure were successfully identified for all drugs studied. • Key recommendations about the compatibility of existing TB therapies as potential LAI candidates were developed.	[16]
Glecaprevir, pibrentasvir	HCV	• To date, the compatibiltiy and optimal release rate for glecaprivir has been identified and work is ongoing to develop models for pibrentasvir and both drugs in combination.	Ongoing work, unpublished

Abbreviations: ARV, ; HCV, hepatitis C virus; LA, long acting; LAI, long-acting injectable; LEAP, Long-Acting/Extended Release Antiretroviral Research Resource Program; RTI, Research Triangle Institute; TAF, tenofovir alafenamide; TB, tuberculosis.