下一代测序技术在确定喀麦隆垂直感染艾滋病毒-1的儿童的耐药性和病毒嗜性方面具有附加价值。
Next-generation sequencing provides an added value in determining drug resistance and viral tropism in Cameroonian HIV-1 vertically infected children.
作者信息
Fokam Joseph, Bellocchi Maria C, Armenia Daniele, Nanfack Aubin J, Carioti Luca, Continenza Fabio, Takou Desire, Temgoua Edith S, Tangimpundu Charlotte, Torimiro Judith N, Koki Paul N, Fokunang Charles N, Cappelli Giulia, Ndjolo Alexis, Colizzi Vittorio, Ceccherini-Silberstein Francesca, Perno Carlo-Federico, Santoro Maria M
机构信息
Chantal Biya International Reference Centre for research on HIV/AIDS Prevention and Management, Yaounde, Cameroon University of Rome Tor Vergata, Rome, Italy University of Yaounde I National HIV Drug Resistance Prevention and Surveillance Working Group, Yaounde, Cameroon New York University School of Medicine, New York, NY National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS, Rome, Italy Mother-Child Center, Chantal BIYA Foundation, Yaounde University of Bamenda, Bamenda, Cameroon National Research Council UNESCO Board of Multidisciplinary Biotechnology, Rome, Italy.
出版信息
Medicine (Baltimore). 2018 Mar;97(13):e0176. doi: 10.1097/MD.0000000000010176.
With limited and low-genetic barrier drugs used for the prevention of mother-to-child transmission (PMTCT) of HIV in sub-Saharan Africa, vertically transmitted HIV-1 drug-resistance (HIVDR) is concerning and might prompt optimal pediatric strategies.The aim of this study was to ascertain HIVDR and viral-tropism in majority and minority populations among Cameroonian vertically infected children.A comparative analysis among 18 HIV-infected children (7 from PMTCT-exposed mothers and 11 from mothers without PMTCT-exposure) was performed. HIVDR and HIV-1 co-receptor usage was evaluated by analyzing sequences obtained by both Sanger sequencing and ultra-deep 454-pyrosequencing (UDPS), set at 1% threshold.Overall, median (interquartile range) age, viremia, and CD4 count were 6 (4-10) years, 5.5 (4.9-6.0) log10 copies/mL, and 526 (282-645) cells/mm, respectively. All children had wild-type viruses through both Sanger sequencing and UDPS, except for 1 PMTCT-exposed infant harboring minority K103N (8.31%), born to a mother exposed to AZT+3TC+NVP. X4-tropic viruses were found in 5 of 15 (33.3%) children (including 2 cases detected only by UDPS). Rate of X4-tropic viruses was 0% (0/6) below 5 years (also as minority species), and became relatively high above 5 years (55.6% [5/9], P = .040. X4-tropic viruses were higher with CD4 ≤15% (4/9 [44.4%]) versus CD4 >15% (1/6 [16.7%], P = .580); similarly for CD4 ≤200 (3/4 [75%]) versus CD4 >200 (2/11 [18.2%] cells/mm, P = .077.NGS has the ability of excluding NRTI- and NNRTI-mutations as minority species in all but 1 children, thus supporting the safe use of these drug-classes in those without such mutations, henceforth sparing ritonavir-boosted protease inhibitors or integrase inhibitors for the few remaining cases. In children under five years, X4-tropic variants would be rare, suggesting vertical-transmission with CCR5-tropic viruses and possible maraviroc usage at younger ages.
在撒哈拉以南非洲地区，用于预防艾滋病毒母婴传播（PMTCT）的药物有限且遗传屏障较低，垂直传播的HIV-1耐药性（HIVDR）令人担忧，可能需要优化儿科治疗策略。本研究的目的是确定喀麦隆垂直感染儿童中多数和少数群体的HIVDR及病毒嗜性。对18名感染艾滋病毒的儿童（7名来自接受过PMTCT的母亲，11名来自未接受过PMTCT的母亲）进行了比较分析。通过分析桑格测序和超深度454焦磷酸测序（UDPS）获得的序列来评估HIVDR和HIV-1共受体使用情况，设定阈值为1%。总体而言，年龄中位数（四分位间距）、病毒血症和CD4细胞计数分别为6（4 - 10）岁、5.5（4.9 - 6.0）log10拷贝/毫升和526（282 - 645）个细胞/立方毫米。除了1名接受过PMTCT的婴儿携带少数K103N突变（8.31%）外，所有儿童通过桑格测序和UDPS检测均为野生型病毒，该婴儿的母亲曾接受齐多夫定+拉米夫定+奈韦拉平治疗。15名儿童中有5名（33.3%）检测到X4嗜性病毒（包括2例仅通过UDPS检测到的病例）。5岁以下儿童中X4嗜性病毒的发生率为0%（0/6）（同样作为少数毒株），5岁以上则相对较高（55.6% [5/9]，P = 0.040）。CD4≤15%时X4嗜性病毒较高（4/9 [44.4%]），而CD4>15%时为（1/6 [16.7%]，P = 0.580）；CD4≤200时情况类似（3/4 [75%]），CD4>200时为（2/11 [18.2%]细胞/立方毫米，P = 0.077）。除1名儿童外，二代测序有能力排除所有儿童中作为少数毒株的核苷类逆转录酶抑制剂和非核苷类逆转录酶抑制剂突变，从而支持在无此类突变的儿童中安全使用这些药物类别，因此对于其余少数病例可避免使用利托那韦增强的蛋白酶抑制剂或整合酶抑制剂。在5岁以下儿童中，X4嗜性变体罕见，提示通过CCR5嗜性病毒进行垂直传播，且在较年幼时可能使用马拉维若。
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