Step-down affordable treatment for chronic hepatitis B infection in Africa and India Acronym - STEP-HEP (360G-Wellcome-099952_Z_12_Z)

Chronic infection with the hepatitis B virus is common throughout the developing world. Effective treatments are too costlyand complex for widespread use leading to signficant preventable morbidity and mortality. We will complete a randomisedcontrolled clinical trial examining a new approach to therapy in which virological response is induced by therapy withexpensive tenofovir and patients are then randomised to either continue tenofovir monotherapy or receive cheaperlamivudine.The primary objective of the study is to determine whether treatment of chronic hepatitis B infection with an inductionmaintenanceregime of tenofovir stepping down to lamivudine is safe and feasible in developing countries. Specifically wewill test the hypothesis that in patients with chronic HBV infection and active liver inflammation, 48 weeks induction therapywith tenofovir can be followed by successful transfer to lamivudine therapy in patients with a 'normal' ALT and any relapsecan be controlled by reintroduction of tenofovir. The primary objective of the study is safety and we will determine whetheran induction-maintenance regime followed by re-introduction of tenofovir in those who fail to respond to lamivudine isinferior to continuous tenofovir.Secondary objectives are:-To determine what proportion of patients can successfully be converted to lamivudine and a critical secondary objective isthe cost effectiveness of this approach.To determine whether treatment modifications can be guided by the use of liver function tests rather than sophisticatedvirological monitoring.