AIDS (London, England) 2017 01 24() doi 10.1097/QAD.0000000000001424
Viral liver diseases are frequent co-morbidities and major contributors to death in HIV-positive individuals on antiretroviral therapy. Whereas cure of hepatitis C and control of hepatitis B with antivirals avert liver disease progression in most HIV-coinfected patients, the lack of satisfactory treatment for hepatitis delta virus (HDV) infection remains a major threat for developing cirrhosis and liver cancer in this population. In the European Union and North America, sexual contact has replaced injection drug use has major transmission route for HDV in HIV-positive persons. Peginterferon alpha is the only approved HDV therapy; however, sustained HDV-RNA clearance is achieved by less than 25%. The recent discovery of NTCP as key HBV and HDV cell entry receptor has opened the door to a new therapeutic era. Indeed, promising results have been released using Myrcludex-B, a NTCP inhibitor. More encouraging are data with new classes of HDV blockers, such as prenylation inhibitors (i.e., Lonafarnib) and nucleic acid polymers. At this time, sustained suppression of HDV replication is the primary goal of HDV therapy, since it is associated with normalization of liver enzymes and histological improvement. Of note, the use of specific antivirals for HDV must be given along with anti-HBV agents, to prevent HBV rebounds following removal of viral interference. The lack of persistent forms of HDV-RNA could provide a unique opportunity for curing hepatitis delta, even without eliminating HBV cccDNA. Ultimately, suppression of HDV replication along with HBsAg clearance once drugs are off would be the best reflect of hepatitis delta cure.