Detection of HIV-1 Transmission Clusters from Dried Blood Spots within a Universal Test-and-Treat Trial in East Africa.
Detection of HIV-1 Transmission Clusters from Dried Blood Spots within a Universal Test-and-Treat Trial in East Africa.
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DOI：
10.3390/v14081673
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发表时间：
2022-07-29
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东非可持续社区健康研究 (SEARCH) 试验是在乌干达和肯尼亚农村地区开展的一项普遍检测与治疗 (UTT) 试验，旨在降低区域 HIV-1 发病率。在这里，我们通过基于人群的干血斑样本量化试验期间发生的突破性 HIV-1 传播。 2013 年至 2017 年间，我们从 745 名参与者那里获得了 549 个 gag 和 488 个 pol HIV-1 共有序列：其中 469 名参与者在试验开始前感染，276 名参与者因 SEARCH 事件感染。根据最大似然系统发育推断出假定的传播簇，其成对遗传距离阈值为 1.5%；搜索开始后出现的簇通过贝叶斯时间校准的系统发育来识别。我们的系统动力学方法确定了搜索开始日期后出现的九个簇：八对和一个三联体，代表大多数异性相关（6/9），社区内传播（7/9）。两个集群包含具有非核苷逆转录酶抑制剂（NNRTI）耐药性的个体，两者都与干预社区有关。对 SEARCH 事件、社区内传播的识别揭示了未受抑制的个体在 UTT 试验环境中维持流行病的作用。传播的 NNRTI 耐药性的存在，意味着 SEARCH 期间使用的基于依非韦伦的抗逆转录病毒疗法 (ART) 的治疗失败，这凸显了需要改进交付和遵守最新 ART 建议，以阻止 HIV-1 传播。
The Sustainable East Africa Research in Community Health (SEARCH) trial was a universal test-and-treat (UTT) trial in rural Uganda and Kenya, aiming to lower regional HIV-1 incidence. Here, we quantify breakthrough HIV-1 transmissions occurring during the trial from population-based, dried blood spot samples. Between 2013 and 2017, we obtained 549 gag and 488 pol HIV-1 consensus sequences from 745 participants: 469 participants infected prior to trial commencement and 276 SEARCH-incident infections. Putative transmission clusters, with a 1.5% pairwise genetic distance threshold, were inferred from maximum likelihood phylogenies; clusters arising after the start of SEARCH were identified with Bayesian time-calibrated phylogenies. Our phylodynamic approach identified nine clusters arising after the SEARCH start date: eight pairs and one triplet, representing mostly opposite-gender linked (6/9), within-community transmissions (7/9). Two clusters contained individuals with non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance, both linked to intervention communities. The identification of SEARCH-incident, within-community transmissions reveals the role of unsuppressed individuals in sustaining the epidemic in both arms of a UTT trial setting. The presence of transmitted NNRTI resistance, implying treatment failure to the efavirenz-based antiretroviral therapy (ART) used during SEARCH, highlights the need to improve delivery and adherence to up-to-date ART recommendations, to halt HIV-1 transmission.
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