Low-frequency drug-resistant HIV-1 and risk of virological failure to first-line NNRTI-based ART: a multicohort European case-control study using centralized ultrasensitive 454 pyrosequencing.
Low-frequency drug-resistant HIV-1 and risk of virological failure to first-line NNRTI-based ART: a multicohort European case-control study using centralized ultrasensitive 454 pyrosequencing.
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DOI：
10.1093/jac/dku426
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发表时间：
2015-03
期刊：
影响因子：
--
通讯作者：
CHAIN Minority HIV-1 Variants Working Group
中科院分区：
文献类型：
--
作者：
Cozzi-Lepri A;Noguera-Julian M;Di Giallonardo F;Schuurman R;Däumer M;Aitken S;Ceccherini-Silberstein F;D'Arminio Monforte A;Geretti AM;Booth CL;Kaiser R;Michalik C;Jansen K;Masquelier B;Bellecave P;Kouyos RD;Castro E;Furrer H;Schultze A;Günthard HF;Brun-Vezinet F;Paredes R;Metzner KJ;CHAIN Minority HIV-1 Variants Working Group
先前存在的少数耐药 HIV-1 变异 (MV) 是否会影响一线 NNRTI 抗逆转录病毒治疗的病毒学结果仍存在争议。这项欧洲范围内的病例对照研究包括未接受过 ART 的受试者，根据群体测序结果显示，这些受试者感染了药物敏感的 HIV-1，这些受试者在一线 ART（包括一种 NNRTI）中实现了病毒学抑制。病例经历了病毒学失败，对照是来自同一队列的受试者，自ART开始以来，其病毒血症在匹配的时间仍然受到抑制。两个实验室采用盲法、集中式 454 焦磷酸测序和并行生物信息学分析来识别 1%–25% 频率范围内的 MV。通过逻辑回归估计根据 MV 检测的病毒学失败的 OR。 260 个样本（76 个病例和 184 个对照）用于分析，其中大部分为 B 亚型（73.5%）。两个实验室检测到相同的 MV。 31.6% 的病例和 16.8% 的对照者携带先前存在的 MV。检测到至少一种 MV 与未检测到 MV 相比，病毒学失败的风险增加相关（OR = 2.75，95% CI = 1.35–5.60，P = 0.005）；至少一种 MV 与无 NRTI MV（OR = 2.27，95% CI = 0.76–6.77，P = 0.140）和至少一种 MV 与无 NNRTI MV（OR = 2.41，95%）观察到类似的关联CI = 1.12–5.18，P = 0.024）。发现病毒学失败和突变负荷之间存在剂量效应关系。预先存在的 MV 会使基于 NNRTI 的一线 ART 病毒学失败的风险增加一倍以上。
It is still debated if pre-existing minority drug-resistant HIV-1 variants (MVs) affect the virological outcomes of first-line NNRTI-containing ART. This Europe-wide case–control study included ART-naive subjects infected with drug-susceptible HIV-1 as revealed by population sequencing, who achieved virological suppression on first-line ART including one NNRTI. Cases experienced virological failure and controls were subjects from the same cohort whose viraemia remained suppressed at a matched time since initiation of ART. Blinded, centralized 454 pyrosequencing with parallel bioinformatic analysis in two laboratories was used to identify MVs in the 1%–25% frequency range. ORs of virological failure according to MV detection were estimated by logistic regression. Two hundred and sixty samples (76 cases and 184 controls), mostly subtype B (73.5%), were used for the analysis. Identical MVs were detected in the two laboratories. 31.6% of cases and 16.8% of controls harboured pre-existing MVs. Detection of at least one MV versus no MVs was associated with an increased risk of virological failure (OR = 2.75, 95% CI = 1.35–5.60, P = 0.005); similar associations were observed for at least one MV versus no NRTI MVs (OR = 2.27, 95% CI = 0.76–6.77, P = 0.140) and at least one MV versus no NNRTI MVs (OR = 2.41, 95% CI = 1.12–5.18, P = 0.024). A dose–effect relationship between virological failure and mutational load was found. Pre-existing MVs more than double the risk of virological failure to first-line NNRTI-based ART.
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影响因子：
3.7
作者：
Di Giallonardo F;Zagordi O;Duport Y;Leemann C;Joos B;Künzli-Gontarczyk M;Bruggmann R;Beerenwinkel N;Günthard HF;Metzner KJ
通讯作者：
Metzner KJ
影响因子：
56.3
作者：
Wittkop, Linda;Guenthard, Huldrych F.;Chene, Genevieve
通讯作者：
Chene, Genevieve
DOI：
10.1097/qad.0b013e32834e9d7d
发表时间：
2012-01-14
期刊：
AIDS (London, England)
影响因子：
--
作者：
Li JZ;Paredes R;Ribaudo HJ;Svarovskaia ES;Kozal MJ;Hullsiek KH;Miller MD;Bangsberg DR;Kuritzkes DR
通讯作者：
Kuritzkes DR
影响因子：
3.7
作者：
Snedecor SJ;Khachatryan A;Nedrow K;Chambers R;Li C;Haider S;Stephens J
通讯作者：
Stephens J
影响因子：
7.7
作者：
Vandenbroucke, Jan P.;Pearce, Neil
通讯作者：
Pearce, Neil