Impact of pretreatment low-abundance HIV-1 drug-resistant variants on virological failure among HIV-1/TB-co-infected individuals.
Impact of pretreatment low-abundance HIV-1 drug-resistant variants on virological failure among HIV-1/TB-co-infected individuals.
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DOI：
10.1093/jac/dkaa343
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发表时间：
2020-11-01
期刊：
影响因子：
--
通讯作者：
De Oliveira T
中科院分区：
文献类型：
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作者：
Chimukangara B;Giandhari J;Lessells R;Yende-Zuma N;Sartorius B;Samuel R;Khanyile KS;Stray-Pedersen B;Moodley P;Metzner KJ;Padayatchi N;Naidoo K;De Oliveira T
为了确定治疗前低丰度HIV-1耐药变异体（LA-DRV）对接受NNRTI一线ART治疗的HIV-1/TB合并感染个体的病毒学失败（VF）的影响，我们对170例HIV-1/TB合并感染成人进行了病例对照研究。在接受基于NNRTI的ART治疗≥6个月后，病例至少有一种病毒载量（VL）≥1000 RNA拷贝/mL，对照组持续VL <1000拷贝/mL。我们通过桑格和MiSeq下一代测序（NGS）对血浆病毒进行测序。我们使用斯坦福大学耐药数据库评估了耐药突变（DRM），并分析了≥ 20%、10%、5%和2%阈值时DRM的NGS数据。我们评估了治疗前耐药（PDR）对VF的影响。我们分析了45例病例和125例对照的序列。在≥20%阈值时检测到的PDR总体患病率为4.7%（8/170），病例组高于对照组（8.9% vs 3.2%），P = 0.210。PDR ≥20%的受试者与无PDR的受试者相比，VF的几率几乎高出4倍（校正OR 3.7，95% CI 0.8-18.3），P = 0.104。当纳入≥2%的LA-DRV时，PDR患病率增加至18.2%（31/170）。与未接受治疗的受试者相比，接受治疗前LA-DRV的受试者发生VF的几率仅高1.6倍（调整后OR 1.6，95% CI 0.6-4.3），P = 0.398。治疗前DRM和LA-DRV增加了基于NNRTI的ART发生VF的几率，但无统计学意义。NGS增加了DRM的检测，但在较低阈值下识别有VF风险的参与者方面没有提供额外的益处。需要更多的研究来评估预测VF的突变阈值，以告知在治疗决策中使用NGS。
To determine the impact of pretreatment low-abundance HIV-1 drug-resistant variants (LA-DRVs) on virological failure (VF) among HIV-1/TB-co-infected individuals treated with NNRTI first-line ART. We conducted a case–control study of 170 adults with HIV-1/TB co-infection. Cases had at least one viral load (VL) ≥1000 RNA copies/mL after ≥6 months on NNRTI-based ART, and controls had sustained VLs <1000 copies/mL. We sequenced plasma viruses by Sanger and MiSeq next-generation sequencing (NGS). We assessed drug resistance mutations (DRMs) using the Stanford drug resistance database, and analysed NGS data for DRMs at ≥20%, 10%, 5% and 2% thresholds. We assessed the effect of pretreatment drug resistance (PDR) on VF. We analysed sequences from 45 cases and 125 controls. Overall prevalence of PDR detected at a ≥20% threshold was 4.7% (8/170) and was higher in cases than in controls (8.9% versus 3.2%), P = 0.210. Participants with PDR at ≥20% had almost 4-fold higher odds of VF (adjusted OR 3.7, 95% CI 0.8–18.3) compared with those without, P = 0.104. PDR prevalence increased to 18.2% (31/170) when LA-DRVs at ≥2% were included. Participants with pretreatment LA-DRVs only had 1.6-fold higher odds of VF (adjusted OR 1.6, 95% CI 0.6–4.3) compared with those without, P = 0.398. Pretreatment DRMs and LA-DRVs increased the odds of developing VF on NNRTI-based ART, although without statistical significance. NGS increased detection of DRMs but provided no additional benefit in identifying participants at risk of VF at lower thresholds. More studies assessing mutation thresholds predictive of VF are required to inform use of NGS in treatment decisions.
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DOI：
10.1093/bioinformatics/bty695
发表时间：
2019-03-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
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作者：
Vilsker M;Moosa Y;Nooij S;Fonseca V;Ghysens Y;Dumon K;Pauwels R;Alcantara LC;Vanden Eynden E;Vandamme AM;Deforche K;de Oliveira T
通讯作者：
de Oliveira T
DOI：
10.1093/cid/ciy881
发表时间：
2019-07-02
期刊：
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
影响因子：
--
作者：
Derache A;Iwuji CC;Baisley K;Danaviah S;Marcelin AG;Calvez V;de Oliveira T;Dabis F;Porter K;Pillay D
通讯作者：
Pillay D
影响因子：
56.3
作者：
Wittkop, Linda;Guenthard, Huldrych F.;Chene, Genevieve
通讯作者：
Chene, Genevieve
影响因子：
16.1
作者：
Avila-Rios, Santiago;Garcia-Morales, Claudia;Reyes-Teran, Gustavo
通讯作者：
Reyes-Teran, Gustavo
影响因子：
15.1
作者：
Chimukangara, Benjamin;Lessells, Richard J.;de Oliveira, Tulio
通讯作者：
de Oliveira, Tulio