LEAP Publications

Tuberculosis (TB) remains a global pandemic and is one of the top ten leading causes of death worldwide, however early diagnosis and anti-TB therapy have saved over 49 million lives between 2000 and 2015. Individuals with latent TB infection (LTBI) along with immunosuppression, including neonates, infants, elderly and patients co-infected with HIV are at higher risk of developing active TB infection. Progression of LTBI to active TB is 12 to 20 times higher in HIV-infected persons than in those who are HIV-uninfected.

Long-acting injectable antiretrovirals represent a pharmacological alternative to oral formulations and an innovative clinical option to address adherence and reduce drug costs. Clinical studies in children and adolescents are characterised by ethical and logistic barriers complicating the identification of dose optimisation. Physiologically-based pharmacokinetic modelling represents a valuable tool to inform dose finding prior to clinical trials. The objective of this study was to simulate potential dosing strategies for existing long-acting injectable depot formulations of cabotegravir and rilpivirine in children and adolescents (aged 3-18 years) using physiologically-based pharmacokinetic modelling.

Every year, Plasmodium falciparum malaria afflicts hundreds of millions of people and kills hundreds of thousands of children. Despite considerable success in reducing the worldwide prevalence of malaria, its incidence in visitors to endemic areas has continued to rise steadily and for unprotected travellers to west Africa the risk of malaria is 3.4% mo−1. Though promising advances are being made, as of yet no malaria vaccine can reliably impart high levels of long-lived protection. Antimalarial drugs thus continue to provide an essential component of malaria prophylaxis. Unfortunately, however, the requirement for daily or weekly oral drug-dosing regimens is commonly associated with noncompliance.

Orally-administered combination antiretroviral drug therapy has had impressive success in suppressing viral replication in HIV-infected individuals and largely protecting them from the complications of HIV-1 infection. Incomplete recovery of the CD4 T cell population and residual immune impairment, mild neurocognitive dysfunction, and a continued risk of cardiovascular and other “non-AIDS” events, all associated with persistent immune activation, remain as problems. But, by and large, the morbidities and mortality from HIV disease have greatly diminished. Furthermore, oral regimens have become simpler and less toxic over time, so that several well tolerated one-pill-a-day coformulated single tablet regimens (STRs) are now available.