LANCET-HBV: Hepatitis B Infection in the Era of Long-Acting ART

About This Grant

Project Summary/Abstract: Long-acting antiretroviral therapy (LA-ART) represents a transformative advance in HIV treatment, including for persons with HIV (PWH) who have HIV viremia. However, LA-ART regimens lack activity against hepatitis B virus (HBV), creating a vulnerability for PWH with prior HBV exposure or HBV non-immunity. Discontinuation of HBV-active antiretrovirals during transitions to LA-ART can lead to HBV reactivation or new HBV infection, resulting in hepatitis flares and death. Despite these risks, there is substantial variability in reported incidence across populations, and most available data derive from observational cohorts or case-based series. Consequently, the incidence, predictors, and biological mechanisms of HBV reactivation and incident infection in the context of LA-ART remain poorly defined, limiting safe implementation of these therapies in the United States and globally. Similarly, patient and provider knowledge, acceptability, and preferences regarding HBV screening and monitoring during LA-ART are not well understood, and the optimal cost-effective approach to HBV screening and monitoring during LA-ART transition is unknown. This project leverages the ACTG LANCET (A5433) clinical trial, which randomizes PWH with viremia to standard-of-care tenofovir/lamivudine/dolutegravir or LA-ART cabotegravir and rilpivirine. This multidisciplinary study integrates clinical and virologic investigations with complementary behavioral science studies and cost- effectiveness analyses. Aim 1 will quantify the incidence, predictors, and clinical consequences of new and reactivation HBV among PWH transitioning to LA-ART and will evaluate novel virologic and serologic biomarkers, including quantitative HBsAg and HBV RNA, to identify early predictors of risk. Aim 2 will assess patient and provider knowledge, preferences, and decision-making around HBV screening, monitoring, and management during LA-ART using surveys and in-depth interviews, and will develop practical tools to support real-world implementation, both using data from A5433 and a separate UCLA and UCSD prospective mixed- methods survey study. Aim 3 will define cost-effective strategies for HBV screening and monitoring during LA- ART transition in the US, Brazil, and Botswana. The results will inform clinical guidelines by defining the true incidence of new and reactivation HBV, establishing evidence-based approaches to HBV screening and monitoring, and identifying the most cost-effective strategies to protect liver health during HIV LA-ART.