Dow Dorothy E, Schimana Werner, Nyombi Balthazar M, Mmbaga Blandina T, Shayo Aisa M, Bartlett John A, Massambu Charles G, Kifaro Emmanuel G, Turner Elizabeth L, DeMarco Todd, Cai Fangping, Cunningham Coleen K, Buchanan Ann M
1 Division of Infectious Diseases, Department of Pediatrics, Duke University Medical Center , Durham, North Carolina.
2 Kilimanjaro Christian Medical Centre , Moshi, Tanzania .
AIDS Res Hum Retroviruses. 2017 Nov;33(11):1107-1113. doi: 10.1089/AID.2017.0025. Epub 2017 Oct 5.
Prevention of mother-to-child transmission (PMTCT) guidelines recommend that all HIV-infected pregnant women receive antiretroviral therapy (Option B) and HIV-infected infants should initiate therapy with a protease inhibitor-based regimen; however, implementation of these guidelines has lagged in many resource-limited settings. Tanzania only recently implemented these guidelines with little country-specific data to inform whether HIV non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance was present among infected infants under the Option A guidelines. This study aimed to identify primary resistance mutations in HIV-infected infants and to identify risk of nevirapine (NVP) resistance based on maternal and infant NVP exposure. Infant dried blood spots (DBSs) were sent to the zonal reference laboratory at Kilimanjaro Christian Medical Centre Clinical Laboratory and underwent DNA polymerase chain reaction testing for HIV as standard of care. Using the clinical laboratory registry, HIV-positive DBS cards, stored at ambient temperature, were identified and sent for further viral load testing, nucleotide sequencing, and analysis. Clinical information was obtained from the PMTCT clinical sites and the National PMTCT registry for information regarding maternal and infant demographics and PMTCT treatment regimen. Results demonstrated that infants exposed to NVP were more likely to have high level resistance mutations (HLRMs) to NVP than those infants not exposed to NVP (p = .002). The most common HLRMs to NVP were K103 N, Y181C, and Y188 L. HIV subtype A was most common, followed by subtype C. Approximately one-third of HIV-infected infants had documented referral to HIV care. This study demonstrated the ongoing need to scale up and strengthen points along the PMTCT continuum and supported the recommendation for all HIV-infected infants to initiate a lopinavir/ritonavir-based antiretroviral therapy regimen.
预防母婴传播（PMTCT）指南建议，所有感染艾滋病毒的孕妇都应接受抗逆转录病毒治疗（方案B），感染艾滋病毒的婴儿应开始使用基于蛋白酶抑制剂的治疗方案；然而，在许多资源有限的环境中，这些指南的实施滞后。坦桑尼亚直到最近才实施这些指南，几乎没有针对该国的具体数据来表明在方案A指南下感染婴儿中是否存在艾滋病毒非核苷类逆转录酶抑制剂（NNRTI）耐药性。本研究旨在确定感染艾滋病毒婴儿中的主要耐药突变，并根据母婴奈韦拉平（NVP）暴露情况确定NVP耐药风险。婴儿干血斑（DBS）被送往乞力马扎罗基督教医疗中心临床实验室的区域参考实验室，并按照标准护理进行艾滋病毒的DNA聚合酶链反应检测。利用临床实验室登记册，识别出保存在室温下的艾滋病毒阳性DBS卡，并送去进行进一步的病毒载量检测、核苷酸测序和分析。从预防母婴传播临床站点和国家预防母婴传播登记册获取临床信息，以了解母婴人口统计学和预防母婴传播治疗方案的信息。结果表明，与未接触NVP的婴儿相比，接触NVP的婴儿更有可能对NVP产生高水平耐药突变（HLRMs）（p = 0.002）。对NVP最常见的HLRMs是K103N、Y181C和Y188L。艾滋病毒A型最常见，其次是C型。大约三分之一感染艾滋病毒的婴儿有转诊接受艾滋病毒治疗的记录。本研究表明，持续需要扩大和加强预防母婴传播连续过程中的各个环节，并支持所有感染艾滋病毒的婴儿开始使用基于洛匹那韦/利托那韦的抗逆转录病毒治疗方案的建议。
