Hepatitis B Virus Containing the I233V Mutation in the Polymerase Reverse‐Transcriptase Domain Remains Sensitive to Inhibition by Adefovir

Maria Curtis, Yuao Zhu, Katyna Borroto‐Esoda
2007 Journal of Infectious Diseases  
An isoleucine-to-valine change at position 233 (rtI233V) of hepatitis B virus (HBV) polymerase was recently reported to cause decreased in vitro susceptibility to, and treatment failure of, adefovir dipivoxil (ADV). To further evaluate these findings, we screened our ADV clinical-study sequence database of 853 patients and identified 4 who, at baseline, had HBV with this mutation. All 4 patients responded to treatment with ADV, with a median change in HBV DNA levels of 4.0 log 10 copies/mL
more » ... g 10 copies/mL after 48 weeks of treatment. Phenotypic evaluation of clinical isolates and of a laboratory strain with the rtI233V mutation demonstrated their full susceptibility to adefovir in vitro, and HBV with the rtI233V mutation developed in none of the patients. Adefovir dipivoxil (ADV) is a nucleotide analogue that is used for the treatment of patients with chronic hepatitis B, including patients infected with HBeAg ϩ or HBeAg Ϫ types of hepatitis B virus (HBV), lamivudine-resistant HBV, liver transplant, and HIV coinfection [1]. On the basis of results on ‫0001ف‬ patients enrolled in clinical studies of ADV, 2 mutations associated with resistance to adefovir were identified in the polymerase region of HBV: rtN236T and rtA181V [2]. These 2 mutations were demonstrated to have a strong correlation with clinical-treatment failure and to confer a statistically significant reduction of drug susceptibility in vitro [3] . The cumulative probability of muta-
doi:10.1086/522521 pmid:18008227 fatcat:5yzaw7kvdrbkvecc4sptus36k4