Deal C, Ajana F, Canva V, Mouton Y, Yazdanpanah Y, Wattré P, Bocket L
Service de virologie, CHRU, bâtiment Paul-Boulanger, 59037 Lille cedex, France.
Ann Biol Clin (Paris). 2002 Sep-Oct;60(5):581-8.
Lamivudine (3TC) is a nucleoside analogue which inhibits replication of HIV and HBV and which is used in the treatment of chronic hepatitis B-infected patients with safety and efficacy. The activity of lamivudine was evaluated by the measurement of DNA-HBV concentration in plasma using a very sensitive assay (1,000 copies/mL) (Amplicor VHB Monitor. Roche). Ten patients chronically infected with hepatitis B (group A) and 24 patients with HIV-1 co-infection (group B) were enrolled. In 9 patients of group A, HBVDNA load was undetectable a median of 3.5 months after the beginning of treatment and remained negative for 2 years with hepatitis Be antigen disappearing and normal alanine aminotransferase concentration. In the last immunodeficient patient, the virus which had been resistant to three interferon treatments, was also resistant to lamivudine. In five patients of group B, HBV DNA load remained undetectable after 18 months with HBe antigen disappearing and baseline concentration of alanine aminotransferase. In the remaining 19 patients after a transient decrease of HBV DNA concentration for one year, HBV DNA load increased again without disappearing of HBe antigen and without decrease of alanine aminotransferase concentration showing lamivudine resistant hepatitis B virus. Mutations in the YMDD motif of the DNA polymerase gene were identified in 11 patients (3 with M550V/I mutation; 7 with M550V/I and L256M mutations; 1 with M550V/I, L526M and V519L mutations). In 6 of these patients, was found a M184V mutation in the VIH polymerase. No correlation could be observed between the mutations detected in the two viruses. Using a sensitive HBV-DNA assay, efficacy of lamivudine for a long time in HBV infected patients was proved. However, the prevalence of lamivudine resistance is related to duration of treatment and it may be necessary to use a multitherapy.
拉米夫定(3TC)是一种核苷类似物,可抑制HIV和HBV的复制,用于治疗慢性乙型肝炎感染患者,具有安全性和有效性。使用非常灵敏的检测方法(1000拷贝/毫升)(Amplicor VHB Monitor,罗氏公司)通过测量血浆中DNA-HBV浓度来评估拉米夫定的活性。招募了10名慢性乙型肝炎感染患者(A组)和24名HIV-1合并感染患者(B组)。在A组的9名患者中,治疗开始后中位数3.5个月时HBVDNA载量检测不到,并且在2年内一直为阴性,乙肝e抗原消失,丙氨酸转氨酶浓度正常。在最后一名免疫缺陷患者中,该病毒对三种干扰素治疗耐药,对拉米夫定也耐药。在B组的5名患者中,18个月后HBV DNA载量检测不到,乙肝e抗原消失,丙氨酸转氨酶浓度恢复到基线水平。在其余19名患者中,HBV DNA浓度在1年内短暂下降后再次升高,乙肝e抗原未消失,丙氨酸转氨酶浓度未降低,显示出对拉米夫定耐药的乙型肝炎病毒。在11名患者中鉴定出DNA聚合酶基因YMDD基序中的突变(3名有M550V/I突变;7名有M550V/I和L256M突变;1名有M550V/I、L526M和V519L突变)。在这些患者中的6名中,发现HIV聚合酶中有M184V突变。在两种病毒中检测到的突变之间未观察到相关性。使用灵敏的HBV-DNA检测方法,证明了拉米夫定在HBV感染患者中长期的疗效。然而,拉米夫定耐药的发生率与治疗持续时间有关,可能有必要采用联合治疗。