We recruited adults with chronic HBV infection from Cape Town, South Africa, identifying individuals with a TDF resistance phenotype, defined as persistent HBV vireamia despite >12 months of TDF treatment. We sequenced HBV DNA using MiSeq Illumina with whole genome target enrichment, and sought potential TDF RAMs, based on a pre-defined list of polymorphisms.
Among 66 individuals with chronic HBV (genotypes A and D), three met our clinical definition for TDF resistance, of whom two were coinfected with HIV. In one participant, the consensus HBV sequence contained nine polymorphisms that have been described in association with TDF resistance. Significant treatment non-adherence in this individual was unlikely, as HIV RNA was suppressed. TDF RAMs were also present in HBV sequences from the other two participants, but other factors including treatment non-adherence may also have had a role in failure of HBV DNA suppression in these cases.
Our findings add to the evidence that RAMs in HBV reverse transcriptase may underpin a TDF resistant phenotype. This is the first time these RAMs have been reported from Africa in association with clinical evidence of TDF resistance.
我们从开普敦招募了患有慢性HBV感染的成年人,南非,确定具有TDF抗性表型的个体,定义为持续HBV病毒血症,尽管TDF治疗>12个月。我们测序HBVDNA使用MiSeqIllumina全基因组靶富集,寻找潜在的TDFRAM,基于预定义的多态性列表。
66例慢性HBV(基因型A和D),三个符合我们对TDF耐药性的临床定义,其中两人同时感染了艾滋病毒。在一个参与者中,HBV共有序列包含9个多态性,这些多态性与TDF耐药相关.该个体不太可能出现明显的治疗不依从性,HIVRNA被抑制。TDFRAM也存在于来自其他两名参与者的HBV序列中,但在这些病例中,包括治疗不依从性在内的其他因素也可能在HBVDNA抑制失败中起作用.
我们的发现增加了HBV逆转录酶中的RAM可能支持TDF抗性表型的证据。这是非洲首次报道这些RAM与TDF耐药性的临床证据有关。