Muhimbili University of Health and Allied Sciences, P.O. Box 650001, Dar es Salaam, Tanzania.
Joint Research Center for Human Retrovirus Infection, Kumamoto University, Kumamoto, Japan.
J Antimicrob Chemother. 2023 Mar 2;78(3):779-787. doi: 10.1093/jac/dkad010.
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.
背景：尽管抗逆转录病毒疗法（ART）得到了扩展，且在坦桑尼亚推出了整合酶抑制剂多替拉韦，但治疗效果并未完全实现。HIV 耐药（HIVDR），包括多替拉韦耐药，可能与 HIV 患者中明显的病毒载量（VL）抑制不佳有关。
目的：确定坦桑尼亚儿童和成人中获得性耐药突变（DRMs）的流行率和模式。
方法：对 866 名儿童和 1173 名成人进行了全国性 HIVDR 横断面调查。对高 HIV VL（≥1000 拷贝/ml）的参与者进行了干血斑和/或血浆基因分型。通过 PCR 扩增 HIV 基因（逆转录酶、蛋白酶和整合酶），并直接测序。使用斯坦福 HIVDR 数据库进行 HIVDR 解读。
结果：对 VL≥1000 拷贝/ml 的 137 名参与者（92 名儿童和 45 名成人）的血液样本进行了 HIVDR 基因分型。HIVDR 的总流行率为 71.5%，儿童和成人中分别有 78.3%和 57.8%存在 DRMs。重要的是，5.8%的参与者存在整合酶抑制剂耐药突变，包括主要耐药突变：Q148K、E138K、G118R、G140A、T66A 和 R263K。还在 62.8%、44.5%和 8%的参与者中检测到 NNRTI、NRTI 和 PI 耐药突变。所有存在主要整合酶抑制剂耐药突变的参与者均携带针对 NRTI 骨干药物的耐药突变。
结论：坦桑尼亚超过 70%的高 HIV 病毒血症患者存在耐药突变。多替拉韦耐药的早期出现令人担忧，这可能会影响坦桑尼亚抗逆转录病毒治疗方案的疗效。
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