HIV-1 Subtype C Drug Resistance Mutations in Heavily Treated Patients Failing Integrase Strand Transfer Inhibitor-Based Regimens in Botswana.
HIV-1 Subtype C Drug Resistance Mutations in Heavily Treated Patients Failing Integrase Strand Transfer Inhibitor-Based Regimens in Botswana.
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DOI：
10.3390/v13040594
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发表时间：
2021-03-31
期刊：
影响因子：
--
通讯作者：
Gaseitsiwe S
中科院分区：
文献类型：
--
作者：
Seatla KK;Maruapula D;Choga WT;Ntsipe T;Mathiba N;Mogwele M;Kapanda M;Nkomo B;Ramaabya D;Makhema J;Mmalane M;Mine M;Kasvosve I;Lockman S;Moyo S;Gaseitsiwe S
有有限的真实世界的突变和病毒学结果的数据，治疗经验的人诊断为HIV-1亚型C（HIV-1 C）谁是失败的整合酶链转移抑制剂为基础的方案。审查了2015年5月至2019年9月期间发送的HIV-1基因型耐药检测（GRT）的表格，并招募了在采样时接受度鲁特韦（DTG）或雷特格韦（RAL）cART治疗时病毒学失败的参与者。对残留血浆样本进行HIV-1 Pol基因的桑格测序，并使用斯坦福大学HIV耐药性数据库进行耐药性突变（DRM）分析。从34名个体中生成40个HIV-1C整合酶序列，其中24人在GRT时接受DTG cART，3人接受RAL cART，7人接受未知（DTG或RAL）锚定cART。11/34例（32%）患者存在DTG和其他整合酶抑制剂的DRM。7/11例（64%）患者在采样时暴露于基于RAL的cART。在11例DRM患者中，1例（9%）为2类，6例（55%）为3类，4例（36%）为4类多药耐药HIV-1C。7/11例（64%）目前病毒学抑制。在4名未被病毒学抑制的患者中，3名患者有广泛的DRM，涉及4类抗逆转录病毒药物，1名患者已死亡。对DTG的耐药性更常发生在暴露于RAL cART的患者中。具有4类DRM加上整合酶T97和E157 Q突变的个体似乎具有更差的结果。需要在经治疗的HIV-1C诊断个体中频繁进行VL监测和GRT。
There are limited real-world mutational and virological outcomes data of treatment-experienced persons diagnosed with HIV-1 subtype C (HIV-1 C) who are failing Integrase Strand Transfer Inhibitor-based regimens. Requisition forms sent for HIV-1 genotypic resistance testing (GRT) between May 2015 and September 2019 were reviewed and participants experiencing virologic failure while on dolutegravir (DTG) or raltegravir (RAL) cART at sampling recruited. Sanger sequencing of the HIV-1 Pol gene was performed from residual plasma samples and drug resistance mutational (DRM) analysis performed using the Stanford University HIV drug resistance database. 40 HIV-1C integrase sequences were generated from 34 individuals, 24 of whom were on DTG cART, three on RAL cART and seven on an unknown (DTG or RAL)-anchored cART at time of GRT. 11/34 (32%) individuals had DRMs to DTG and other integrase inhibitors. 7/11 (64%) patients had exposure to a RAL-based cART at the time of sampling. Out of the 11 individuals with DRMs, one (9%) had 2-class, 6 (55%) had 3-class, and 4 (36%) had 4-class multidrug-resistant HIV-1C. 7/11 individuals (64%) are currently virologically suppressed. Of the four individuals not virologically suppressed, three had extensive DRMs involving 4-classes of ARV drugs and one individual has demised. Resistance to DTG occurs more often in patients exposed to RAL cART. Individuals with 4-class DRMs plus integrase T97 and E157Q mutations appear to have worse outcomes. There is a need for frequent VL monitoring and GRT amongst treatment-experienced HIV-1C diagnosed individuals.
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影响因子：
1.2
作者：
Boyd SD;Maldarelli F;Sereti I;Ouedraogo GL;Rehm CA;Boltz V;Shoemaker D;Pau AK
通讯作者：
Pau AK
DOI：
10.2147/dddt.s84850
发表时间：
2015
期刊：
Drug design, development and therapy
影响因子：
--
作者：
Kandel CE;Walmsley SL
通讯作者：
Walmsley SL
影响因子：
16.6
作者：
Siedner MJ;Moorhouse MA;Simmons B;de Oliveira T;Lessells R;Giandhari J;Kemp SA;Chimukangara B;Akpomiemie G;Serenata CM;Venter WDF;Hill A;Gupta RK
通讯作者：
Gupta RK
DOI：
10.1097/qai.0000000000001193
发表时间：
2017-02-01
期刊：
Journal of acquired immune deficiency syndromes (1999)
影响因子：
--
作者：
Huhn GD;Tebas P;Gallant J;Wilkin T;Cheng A;Yan M;Zhong L;Callebaut C;Custodio JM;Fordyce MW;Das M;McCallister S
通讯作者：
McCallister S
在博茨瓦纳（Botswana）的基于Dolutegravir的抗逆转录病毒疗法上经历的治疗中，有四类耐药的HIV-1亚型C经验丰富的个体。
DOI：
10.1097/qad.0000000000001920
发表时间：
2018-08-24
期刊：
AIDS (London, England)
影响因子：
--
作者：
Seatla KK;Avalos A;Moyo S;Mine M;Diphoko T;Mosepele M;Gaolatlhe T;Rowley CF;Ramaabya D;Jarvis JN;Kasvosve I;Gaseitsiwe S
通讯作者：
Gaseitsiwe S