Rey D, Fritsch S, Schmitt C, Partisani M, Kempf-Durepaire G, Nicolle M, Krantz V, De Mautort E, Stoll-Keller F, Lang J M
Centre d'Informations et de Soins de l'Immunodéficience Humaine, Clinique Médicale A, Hôpitaux Universitaires, Strasbourg.
Gastroenterol Clin Biol. 2000 Jan;24(1):125-7.
Seven patients co-infected with hepatitis B virus (HBsAg and HBeAg carriers, quantifiable HBV DNA with the bDNA technic) and human immunodeficiency virus received a triple antiretroviral combination therapy, including lamivudine (150 mg twice a day). Hepatitis B viral load rapidly became undetectable in 6/7 patients. It remained below the level of detection in 2 subjects, after 20 and 22 months of treatment, with one of them achieving HBeAg/anti-HBe seroconversion. However, in the other 4 individuals, hepatitis B viremia increased again after 8 to 16 months of lamivudine-containing regimen. The last patient was a non-responder. The 4 relapsers developed a double mutation Leu(528) for Met(528) and Met(552) for Val(552), on hepatitis B virus polymerase, either concomitant (M8 and M16) with a hepatitis B virus DNA increase, or 2 months earlier (M10 and M12). The high frequency of hepatitis B virus resistance to lamivudine emphasizes the necessity of identifying more effective strategies, such as double combination therapies.
7例同时感染乙肝病毒（乙肝表面抗原和乙肝e抗原携带者，采用分支DNA技术可定量检测乙肝病毒DNA）和人类免疫缺陷病毒的患者接受了包含拉米夫定（每日2次，每次150毫克）的三联抗逆转录病毒联合治疗。7例患者中有6例的乙肝病毒载量迅速变得无法检测到。在2例患者中，经过20个月和22个月的治疗后，乙肝病毒载量仍低于检测水平，其中1例实现了乙肝e抗原/乙肝e抗体血清学转换。然而，在其他4例患者中，含拉米夫定方案治疗8至16个月后，乙肝病毒血症再次升高。最后1例患者治疗无反应。4例复发患者的乙肝病毒聚合酶出现了亮氨酸（528）突变为甲硫氨酸（528）以及甲硫氨酸（552）突变为缬氨酸（552）的双重突变，要么与乙肝病毒DNA增加同时出现（第8个月和第16个月），要么在乙肝病毒DNA增加前2个月出现（第10个月和第12个月）。乙肝病毒对拉米夫定的高耐药率凸显了确定更有效策略（如双重联合治疗）的必要性。
