Bihl Florian, Martinetti Gladys, Wandeler Gilles, Weber Rainer, Ledergeber Bruno, Calmy Alexandra, Battegay Manuel, Cavassini Matthias, Vernazza Pietro, Caminada Anna-Paola, Rickenbach Martin, Bernasconi Enos
Cantonal Hepatobiliary Unit, Ente Ospedaliera Cantonale, Ospedale San Giovanni Bellinzona,Switzerland and Gastroenterology and Hepatology Service, University Hospital of Geneva, Geneva, Switzerland.
Institute of Microbiology, Ente Ospedaliera Cantonale, Bellinzona, Switzerland.
BMC Gastroenterol. 2015 Jul 8;15:79. doi: 10.1186/s12876-015-0308-0.
Hepatitis B virus (HBV) genotypes can influence treatment outcome in HBV-monoinfected and human immunodeficiency virus (HIV)/HBV-coinfected patients. Tenofovir disoproxil fumarate (TDF) plays a pivotal role in antiretroviral therapy (ART) of HIV/HBV-coinfected patients. The influence of HBV genotypes on the response to antiviral drugs, particularly TDF, is poorly understood.
HIV/HBV-co-infected participants with detectable HBV DNA prior to TDF therapy were selected from the Swiss HIV Cohort Study. HBV genotypes were identified and resistance testing was performed prior to antiviral therapy, and in patients with delayed treatment response (>6 months). The efficacy of TDF to suppress HBV (HBV DNA <20 IU/mL) and the influence of HBV genotypes were determined.
143 HIV/HBV-coinfected participants with detectable HBV DNA were identified. The predominant HBV genotypes were A (82 patients, 57 %); and D (35 patients, 24 %); 20 patients (14 %) were infected with multiple genotypes (3 % A + D and 11 % A + G); and genotypes B, C and E were each present in two patients (1 %). TDF completely suppressed HBV DNA in 131 patients (92 %) within 6 months; and in 12 patients (8 %), HBV DNA suppression was delayed. No HBV resistance mutations to TDF were found in patients with delayed response, but all were infected with HBV genotype A (among these, 5 patients with genotype A + G), and all had previously been exposed to lamivudine.
In HIV/HBV-coinfected patients, infection with multiple HBV genotypes was more frequent than previously reported. The large majority of patients had an undetectable HBV viral load at six months of TDF-containing ART. In patients without viral suppression, no TDF-related resistance mutations were found. The role of specific genotypes and prior lamivudine treatment in the delayed response to TDF warrant further investigation.
乙型肝炎病毒(HBV)基因型可影响单纯HBV感染以及人类免疫缺陷病毒(HIV)/HBV合并感染患者的治疗结果。替诺福韦酯(TDF)在HIV/HBV合并感染患者的抗逆转录病毒治疗(ART)中起关键作用。HBV基因型对抗病毒药物尤其是TDF反应的影响尚不清楚。
从瑞士HIV队列研究中选取TDF治疗前可检测到HBV DNA的HIV/HBV合并感染参与者。在抗病毒治疗前以及治疗反应延迟(>6个月)的患者中鉴定HBV基因型并进行耐药检测。确定TDF抑制HBV(HBV DNA<20 IU/mL)的疗效以及HBV基因型的影响。
共鉴定出143例可检测到HBV DNA的HIV/HBV合并感染参与者。主要的HBV基因型为A(82例患者,57%)和D(35例患者,24%);20例患者(14%)感染了多种基因型(3%A+D和11%A+G);基因型B、C和E各有2例患者(1%)。131例患者(92%)在6个月内TDF完全抑制了HBV DNA;12例患者(8%)的HBV DNA抑制延迟。延迟反应患者中未发现对TDF的HBV耐药突变,但所有患者均感染HBV基因型A(其中5例为A+G基因型),且均曾接触过拉米夫定。
在HIV/HBV合并感染患者中,多种HBV基因型感染比先前报道的更为常见。在含TDF的ART治疗6个月时,绝大多数患者的HBV病毒载量不可检测。在未实现病毒抑制的患者中,未发现与TDF相关的耐药突变。特定基因型和先前拉米夫定治疗在TDF延迟反应中的作用值得进一步研究。