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在 HIV/乙型肝炎病毒 (HBV) 合并感染个体中长期使用替诺福韦不会导致 HBV 聚合酶突变,并与拉米夫定 HBV 聚合酶突变的持续存在相关。

Prolonged use of tenofovir in HIV/hepatitis B virus (HBV)-coinfected individuals does not lead to HBV polymerase mutations and is associated with persistence of lamivudine HBV polymerase mutations.

机构信息

Monash University, Melbourne, VIC, Australia.

出版信息

HIV Med. 2009 Apr;10(4):229-35. doi: 10.1111/j.1468-1293.2008.00675.x. Epub 2009 Jan 28.

Abstract

OBJECTIVES

The aim of the study was to identify and characterize hepatitis B virus (HBV) polymerase gene mutations associated with ongoing HBV replication in HIV/HBV-coinfected individuals receiving tenofovir (TDF).

METHODS

This retrospective cross-sectional study identified 28 HIV/HBV-coinfected individuals who had received TDF for at least 3 months. All patients had samples available while receiving TDF (on-TDF), and 24 also had samples available prior to treatment (pre-TDF). Case records were reviewed to obtain clinical and virological data at the times of sampling (+/-3 months). The HBV DNA of all samples was amplified using polymerase chain reaction (PCR), and the polymerase region of PCR-positive samples was sequenced and compared with reference HBV data.

RESULTS

Of the pre-TDF samples, 15 of 24 (63%) were HBV PCR positive. Of the on-TDF samples, four of 28 (14%) were HBV PCR positive (mean time on TDF 13.5 months; range 3-23 months). Lamivudine (3TC)-resistance mutations were detected in three of four (75%) of these viraemic samples. The previously identified putative TDF-resistance mutations, rtA194T+rtL180M+rtM204V, were not detected in any individual.

CONCLUSIONS

Unique mutations in the HBV polymerase gene associated with TDF resistance are rare in HIV/HBV coinfection. 3TC-resistance mutations persist and a significant proportion of patients are HBV PCR positive despite the addition of TDF.

摘要

目的

本研究旨在鉴定和描述与接受替诺福韦(TDF)治疗的 HIV/HBV 合并感染个体中持续 HBV 复制相关的乙型肝炎病毒(HBV)聚合酶基因突变。

方法

本回顾性横断面研究纳入了 28 例至少接受 TDF 治疗 3 个月的 HIV/HBV 合并感染患者。所有患者在接受 TDF 治疗时(治疗时)均有样本可用,24 例患者在治疗前(治疗前)也有样本可用。回顾病历以获取采样时(+/-3 个月)的临床和病毒学数据。所有样本的 HBV DNA 均采用聚合酶链反应(PCR)扩增,PCR 阳性样本的聚合酶区域进行测序,并与参考 HBV 数据进行比较。

结果

在治疗前样本中,24 例中有 15 例(63%)HBV PCR 阳性。在治疗时样本中,28 例中有 4 例(14%)HBV PCR 阳性(TDF 治疗时间中位数为 13.5 个月;范围 3-23 个月)。在这 4 例病毒血症样本中,有 3 例(75%)检测到拉米夫定(3TC)耐药突变。未在任何个体中检测到先前鉴定的推定 TDF 耐药突变,rtA194T+rtL180M+rtM204V。

结论

在 HIV/HBV 合并感染中,与 TDF 耐药相关的 HBV 聚合酶基因的独特突变很少见。尽管添加了 TDF,但 3TC 耐药突变仍然存在,且很大一部分患者 HBV PCR 阳性。

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