Phenotypic Susceptibility to Antiretrovirals Among Clades C, F, and B/F Recombinant Antiretroviral-Naive HIV Type 1 Strains

Phenotypic Susceptibility to Antiretrovirals Among Clades C, F, and B/F Recombinant Antiretroviral-Naive HIV Type 1 Strains
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DOI:
10.1089/aid.2012.0259
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发表时间:
2013-06-01
影响因子:
1.5
通讯作者:
Diaz, Ricardo Sobhie
Diaz, Ricardo Sobhie
中科院分区:
医学4区
文献类型:
--
作者:
Sucupira, Maria Cecilia A.;Munerato, Patricia;Diaz, Ricardo Sobhie

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为了评估巴西流行的野生型 HIV-1 毒株的抗逆转录病毒表型敏感性,使用抗病毒谱分析(Virco,梅赫伦,比利时)对来自感染 C 亚型(n = 16)、F(n = 9)或 B/F(n = 7)亚型(其中逆转录酶为 B,蛋白酶为 F)的未接受过抗逆转录病毒治疗的个体的样本进行了表型分析。在 1 个 C 分离株和 3 个 F 分离株中观察到对蛋白酶抑制剂 (PI) 的敏感性降低。这些样本均未发现任何已知的 PI 抗性突变。在 96 个分支 F 表型测定中的 3 个 (3.1%) 和 96 个分支 C 之一 (1.0%) 中,一种 PI 的表型倍数变化高于生物学截止值。在 2 个 B/F、4 个 C 和 3 个 F 分离株中发现了对至少一种核苷逆转录酶抑制剂 (NRTI) 的表型抗性。对 NRTI 易感性的表型倍数变化在 111 次 C 类测定中的 9 次 (8.1%) 中高于截止值,而对于 F 类,63 次中有 3 次 (4.8%),对 B 类 49 次中的 2 次 (4.1%)。非 NRTI (NNRTI) 的表型倍数变化在 32 次中的 7 次 (21.9%) 中高于截止值。 C 菌株的测定结果显示,而 F 菌株的敏感性均未降低。 16 个 C 样本中只有两个具有已知的 NNRTI 抗性突变。在巴西 B/F 重组体(代表进化枝 B 逆转录酶)的 14 次表型测定中,有 3 次 (21.4%) 的 NNRTI 倍数变化高于截止值。应在进化枝 C 和 B/F 重组体中更好地研究 NNRTI 敏感性。
To evaluate antiretroviral phenotypic susceptibility of wild-type HIV-1 strains circulating in Brazil, samples from antiretroviral-naive individuals infected with subtypes C (n = 16), F (n = 9), or B/F (n = 7), where reverse transcriptase is B and protease is F, were phenotyped using the Antivirogram Assay (Virco, Mechelen, Belgium). Reduced susceptibility to protease inhibitors (PIs) was observed in one C and three F isolates. None of these samples had any known PI resistance mutations. The phenotypic fold change to one PI was above the biological cut-off in three of 96 (3.1%) clade F phenotypic determinations and in one of 96 (1.0%) clade C. Phenotypic resistance to at least one nucleoside reverse transcriptase inhibitor (NRTI) was found for two B/F, four C, and three F isolates. The phenotypic fold change in susceptibility to NRTIs was above the cut-off value in nine of 111 (8.1%) clade C determinations, as compared to three of 63 (4.8%) for clade F and two of 49 (4.1%) for clade B. The phenotypic fold change to non-NRTI (NNRTI) was above the cut-off in seven of 32 (21.9%) of C isolates determinations, whereas none of the F isolates had a decrease of susceptibility. Only two of the 16 C samples had a known NNRTI resistance mutation. The NNRTI fold change was above the cut-off value in three of 14 (21.4%) phenotypic determinations of Brazilian B/F recombinants, representing clade B reverse transcriptase. NNRTI susceptibility should be better investigated in clade C and B/F recombinants.