Emerging integrase strand transfer inhibitor drug resistance mutations among children and adults on ART in Tanzania: findings from a national representative HIV drug resistance survey
Emerging integrase strand transfer inhibitor drug resistance mutations among children and adults on ART in Tanzania: findings from a national representative HIV drug resistance survey
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DOI：
10.1093/jac/dkad010
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发表时间：
2023-01-21
影响因子：
5.2
通讯作者：
Sunguya, Bruno
中科院分区：
文献类型：
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作者：
Kamori, Doreen;Barabona, Godfrey;Sunguya, Bruno
背景：尽管抗逆转录病毒治疗的规模已经扩大，整合酶链转移抑制剂多洛替格列韦(Dolutegravir，INSTI)也在坦桑尼亚推出，但治疗的成功尚未完全实现。HIV耐药(HIVDR)，包括多洛替格列韦耐药，可能与HIV患者显著的病毒载量(VL)抑制有关。目的了解坦桑尼亚儿童和成人获得性耐药突变(DRM)的流行情况和模式。方法对866名儿童和1173名成人进行HIVDR横断面调查。对HIV VL高(>；=1000拷贝/毫升)的参与者的干血点和/或血浆进行基因分型。用聚合酶链式反应扩增HIV基因(逆转录酶、蛋白水解酶和整合酶)并直接测序。使用斯坦福大学HIVDR数据库进行HIVDR解释。结果对137名受试者(92名儿童和45名成人)进行了HIVDR基因分型，VL>；=1000拷贝/毫升。HIV DRM的总流行率为71.5%，其中78.3%的儿童和57.8%的成年人存在DRM。重要的是，5.8%的参与者拥有INSTI DRM，包括主要的DRM：Q148K、E138K、G118R、G140A、T66A和R263K。NNRTI、NRTI和PI DRM的阳性率分别为62.8%、44.5%和8%。所有有主要INSTI DRM的参与者都有针对NRTI骨干药物的DRM。结论坦桑尼亚10例高HIV病毒血症患者中有7例以上存在DRM。早期出现多洛替格列韦抗药性令人担忧坦桑尼亚ART方案的效果。
Background Despite the scale-up of ART and the rollout in Tanzania of dolutegravir, an integrase strand transfer inhibitor (INSTI), treatment success has not been fully realized. HIV drug resistance (HIVDR), including dolutegravir resistance, could be implicated in the notable suboptimal viral load (VL) suppression among HIV patients. Objectives To determine the prevalence and patterns of acquired drug resistance mutations (DRMs) among children and adults in Tanzania. Methods A national cross-sectional HIVDR survey was conducted among 866 children and 1173 adults. Genotyping was done on dried blood spot and/or plasma of participants with high HIV VL (>= 1000 copies/mL). HIV genes (reverse transcriptase, protease and integrase) were amplified by PCR and directly sequenced. The Stanford HIVDR Database was used for HIVDR interpretation. Results HIVDR genotyping was performed on blood samples from 137 participants (92 children and 45 adults) with VL >= 1000 copies/mL. The overall prevalence of HIV DRMs was 71.5%, with DRMs present in 78.3% of children and 57.8% of adults. Importantly, 5.8% of participants had INSTI DRMs including major DRMs: Q148K, E138K, G118R, G140A, T66A and R263K. NNRTI, NRTI and PI DRMs were also detected in 62.8%, 44.5% and 8% of participants, respectively. All the participants with major INSTI DRMs harboured DRMs targeting NRTI backbone drugs. Conclusions More than 7 in 10 patients with high HIV viraemia in Tanzania have DRMs. The early emergence of dolutegravir resistance is of concern for the efficacy of the Tanzanian ART programme.