Journal of Medical Virology 84:1340–1343 (2012) Case Report: Management and HBV Sequencing in a Patient Co-Infected With HBV and HIV Failing Tenofovir Malgorzata Mikulska, 1 * Lucia Taramasso, 1 Daniele Roberto Giacobbe, 1 Patrizia Caligiuri, 2 Bianca Bruzzone, 3 Antonio Di Biagio, 1 and Claudio Viscoli 1 1 Division of Infectious Diseases, San Martino University Hospital and University of Genoa, Genoa, Italy 2 Department of Health Sciences, University of Genoa, Genoa, Italy 3 Hygiene Unit, San Martino Hospital, Genoa, Italy Nucleos(t)ide analogs such as tenofovir, lami- vudine, or emtricitabine are active against both HBV and HIV. Tenofovir confers potent and du- rable HBV-DNA suppression but the best strate- gy in case of resistance of HBV to tenofovir remains unknown. A case of a 22-year-old pa- tient with co-infection with HBV and HIV trans- mitted perinatally is reported. After prolonged and intermittent treatment of HIV with lamivu- dine and tenofovir, HBV became resistant to lamivudine. Subsequently, clinical resistance to tenofovir occurred, manifesting as HBV-DNA breakthrough. The non-compliance was reason- able excluded and HIV-RNA remained constant- ly suppressed. Entecavir (1 mg daily) was added and the combination therapy resulted in a rapid and continuous suppression of HBV- DNA for over 12 months. The treatment was well-tolerated and safe. No known mutations, such as rtA181T/V associated with rtN236T or A194T that are associated with reduced suscep- tibility or resistance to tenofovir were detected. However, a unique and complex HBV substitu- tion pattern was found: with a development of rtR192PR mutation at the time of virological failure. Adding entecavir to failing therapy with tenofovir and emtricitabine was feasible, well-tolerated and resulted in virological suc- cess. The rtR192PR, which is located in the B domain near the rtA194T, occurring in a context of a very complex substitutions patterns, might be associated with resistance to teno- fovir. J. Med. Virol. 84:1340–1343, 2012. ß 2012 Wiley Periodicals, Inc. KEY WORDS: entecavir; resistance; R192PR mutation; TDF resistance INTRODUCTION The treatment of chronic hepatitis B in patients co- infected with HBV and HIV represents a difficult challenge for clinicians, because the risk of progres- sion to cirrhosis, end-stage liver disease, and hepato- cellular carcinoma remains high [DHHS, 2011]. Additionally, many antivirals are active against both viruses, thus one virus may develop resistance to an antiviral while the other remains susceptible [DHHS, 2011]. Indeed, the prolonged course of treatment with nucleos(t)ide analogs for HIV therapy may lead to the development of HBV resistance, resulting in virologi- cal and clinical breakthrough; while the opposite might happen, as well [Lok et al., 2007; EASL, 2009]. Tenofovir (TDF) has shown great potency in terms of HBV-DNA suppression and therefore, in association with emtricitabine (FTC) and a third agent, repre- sents a mainstay in the treatment of patients co- infected with HBV and HIV who require antiretrovi- ral therapy [EASL, 2009; DHHS, 2011]. However, the best strategy in case of breakthrough increase of HBV viral load under TDF remains unknown. A patient in whom TDF apparently failed in controlling HBV-DNA is described. He was successfully rescued by adding entecavir (ETV) to a TDF/FTC antiretroviral regimen. The genotypic characteristics of the HBV virus This article is dedicated to the memory of Dr. Raffaella Rosso who for years cared for this patient. The authors declare that there were no conflicts of interest. *Correspondence to: Malgorzata Mikulska, MD, Division of Infectious Diseases, San Martino University Hospital, L.go R. Benzi, 10–16132 Genoa, Italy. E-mail: m.mikulska@unige.it Accepted 3 May 2012 DOI 10.1002/jmv.23338 Published online in Wiley Online Library (wileyonlinelibrary.com). ß 2012 WILEY PERIODICALS, INC.