IMPAACT 2041: Designing the Study of Glecaprevir/Pibrentasvir Treatment During Pregnancy

The significant increase in hepatitis C virus (HCV) infection prevalence among young adults, including those who may become pregnant, has led to a corresponding increase in the number of infants exposed to and infected with HCV. Despite a recommendation for universal HCV screening during pregnancy, there is not always a clear pathway to immediately initiate treatment for maternal cure, which could also prevent vertical transmission like the approach for human immunodeficiency virus (HIV) or hepatitis B virus. In 2019, the American Association for the Study of Liver Diseases/Infectious Diseases Society of America HCV Guidelines panel endorsed the use of shared decision making between providers and patients when considering HCV treatment during pregnancy. Direct-acting antivirals, including glecaprevir/pibrentasvir (GLE/PIB), have been tremendously effective in curing >95% of individuals who begin treatment along with an overall well-characterized safety profile, but data supporting their use when initiated during pregnancy are more limited. International Maternal Pediatric Adolescent AIDS Clinical Trials 2041 is a multicenter single-arm phase I/II clinical trial designed to evaluate the pharmacokinetics and safety of GLE/PIB treatment initiated in pregnant women with HCV mono-infection or HCV/HIV co-infection. In this paper, we describe the relevant background data assembled from various sources to write the protocol and design the study.