Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden.
Department of Microbiology, Immunology and Parasitology, Addis Ababa University, Addis Ababa, Ethiopia.
Sci Rep. 2018 May 15;8(1):7556. doi: 10.1038/s41598-018-25888-6.
Baseline plasma samples of 490 randomly selected antiretroviral therapy (ART) naïve patients from seven hospitals participating in the first nationwide Ethiopian HIV-1 cohort were analysed for surveillance drug resistance mutations (sDRM) by population based Sanger sequencing (PBSS). Also next generation sequencing (NGS) was used in a subset of 109 baseline samples of patients. Treatment outcome after 6- and 12-months was assessed by on-treatment (OT) and intention-to-treat (ITT) analyses. Transmitted drug resistance (TDR) was detected in 3.9% (18/461) of successfully sequenced samples by PBSS. However, NGS detected sDRM more often (24%; 26/109) than PBSS (6%; 7/109) (p = 0.0001) and major integrase strand transfer inhibitors (INSTI) DRMs were also found in minor viral variants from five patients. Patients with sDRM had more frequent treatment failure in both OT and ITT analyses. The high rate of TDR by NGS and the identification of preexisting INSTI DRMs in minor wild-type HIV-1 subtype C viral variants infected Ethiopian patients underscores the importance of TDR surveillance in low- and middle-income countries and shows added value of high-throughput NGS in such studies.
对来自参与首次全国埃塞俄比亚 HIV-1 队列的 7 家医院的 490 名随机选择的抗逆转录病毒治疗 (ART) 初治患者的基线血浆样本进行了基于人群的 Sanger 测序 (PBSS) 以分析监测耐药突变 (sDRM)。还使用了 109 名基线患者样本的下一代测序 (NGS) 子集。通过治疗中 (OT) 和意向治疗 (ITT) 分析评估 6 个月和 12 个月后的治疗结果。通过 PBSS 在成功测序的样本中检测到 3.9%（18/461）的传播耐药性 (TDR)。然而，NGS 比 PBSS 更频繁地检测到 sDRM（24%；26/109）比 PBSS（6%；7/109）（p=0.0001），并且还从五名患者的少数野生型 HIV-1 亚型 C 病毒变异体中发现了主要整合酶链转移抑制剂 (INSTI) 耐药突变。在 OT 和 ITT 分析中，具有 sDRM 的患者治疗失败的频率更高。NGS 检测到的 TDR 率高，以及在感染埃塞俄比亚患者的少数野生型 HIV-1 亚型 C 病毒变异体中发现预先存在的 INSTI 耐药突变，突显了在中低收入国家进行 TDR 监测的重要性，并显示了高通量 NGS 在这类研究中的附加价值。
