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替诺福韦作为挽救治疗对合并感染HIV患者的乙型肝炎病毒DNA长期抑制的证据。

Evidence of long-term suppression of hepatitis B virus DNA by tenofovir as rescue treatment in patients coinfected by HIV.

作者信息

Quiros-Roldan Eugenia, Calabresi Alessandra, Lapadula Giuseppe, Tirelli Valeria, Costarelli Silvia, Cologni Giuliana, Zaltron Serena, Puoti Massimo, Carosi Giampiero, Torti Carlo

机构信息

Institute for Infectious and Tropical Diseases, University of Brescia, Brescia, Italy.

出版信息

Antivir Ther. 2008;13(3):341-8.

Abstract

BACKGROUND

The efficacy of long-term hepatitis B virus (HBV) treatment with tenofovir (TDF) in relation to lamivudine (LMV) resistance in HIV patients failing on LMV deserves further investigations.

METHODS

HIV-HBV coinfected patients were selected, provided that LMV was included in the first highly active antiretroviral therapy regimen and TDF was subsequently introduced.

RESULTS

Forty HIV-HBV patients were included, 25 had undetectable HBV DNA on LMV and 15 were failing on LMV treatment. Three cases of triple 173V + 180M + 204V HBV reverse transcriptase (rt) mutants were identified, as well as several mutations or polymorphisms in the surface antigen gene at positions possibly correlating with vaccine escape. A new mutation (rtl233V) was found in one adefovir-naive patient. In 10 patients, uninterrupted TDF treatment led to a sustained treatment response for a median of 160 (interquartile range 111-189) weeks. Two patients underwent intermittent treatment with TDF and LMV, responding any time TDF was reintroduced. In one patient, TDF without LMV provided treatment response. One patient did not respond to TDF because of low treatment adherence. One patient infected with the triple rt mutant did not respond to entecavir, but TDF was successful as rescue.

CONCLUSIONS

Combination therapy with TDF was effective against HBV mutant viruses resistant to LMV and provided sustained control of HBV replication over long-term follow-up, even after entecavir failure. Moreover, suppression of HBV vaccine escape variants could provide important benefits from a public health perspective.

摘要

背景

对于在拉米夫定(LMV)治疗中失败的HIV患者,长期使用替诺福韦(TDF)治疗乙型肝炎病毒(HBV)的疗效与LMV耐药性的关系值得进一步研究。

方法

选择HIV-HBV合并感染患者,前提是LMV包含在首个高效抗逆转录病毒治疗方案中,随后引入TDF。

结果

纳入40例HIV-HBV患者,25例患者使用LMV时HBV DNA检测不到,15例患者LMV治疗失败。鉴定出3例三重173V + 180M + 204V HBV逆转录酶(rt)突变体,以及表面抗原基因中可能与疫苗逃逸相关位置的若干突变或多态性。在1例未使用过阿德福韦的患者中发现了一个新突变(rtl233V)。10例患者接受不间断TDF治疗,持续治疗反应的中位数为160(四分位间距111 - 189)周。2例患者接受TDF和LMV间歇治疗,每次重新引入TDF时均有反应。1例患者单独使用TDF获得治疗反应。1例患者因治疗依从性低对TDF无反应。1例感染三重rt突变体的患者对恩替卡韦无反应,但TDF挽救治疗成功。

结论

TDF联合治疗对耐LMV的HBV突变病毒有效,并且在长期随访中能持续控制HBV复制,即使在恩替卡韦治疗失败后也是如此。此外,从公共卫生角度来看,抑制HBV疫苗逃逸变异体可能带来重要益处。

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