Sylla M, Dolo O, Maiga A I, Traore F T, Coulibaly Y A, Togo J, Fofana D B, Dicko-Traore F, Doumbia S, Orsega S, Diallo S, Murphy R L, Calvez V, Marcelin A G
Department of Pediatrics, University Hospital Gabriel Toure, Bamako, Mali; Unit for Epidemiology and Molecular of HIV Drug Resistance, SEREFO/UCRC, FMOS, University of Sciences, Techniques and Technologies of Bamako (USTTB), Bamako, Mali.
Unit for Epidemiology and Molecular of HIV Drug Resistance, SEREFO/UCRC, FMOS, University of Sciences, Techniques and Technologies of Bamako (USTTB), Bamako, Mali.
Arch Pediatr. 2019 Jul;26(5):254-258. doi: 10.1016/j.arcped.2019.06.002. Epub 2019 Jul 12.
In recent years, children born to HIV-infected mothers have been receiving antiretroviral treatment (ART) with limited or no virologic monitoring, which increases the likelihood of development and accumulation of drug resistance mutations, which itself may limit the effectiveness of future ART. The objective of this study was to evaluate the prevalence of resistance mutations in children infected with HIV-1 experiencing virological failure to second-line ART in the Pediatric Department of Gabriel Touré Hospital in Mali.
Children aged from 5 to 18 infected with HIV-1 on second-line antiretroviral therapy and whose viral load was greater than 1000 copies/mL after observance reinforcement were enrolled. The protease and reverse transcriptase genes were sequenced with ViroSeq. The results were interpreted according to the last version of the Stanford algorithm in 2018. The study was approved by the Ethics Committee of the Faculty of Medicine and Dentistry, University of Sciences, Techniques and Technologies of Bamako (Mali).
Of 216 children, 33 (15.3%) who had a viral load (VL)>1000 copies/mL in second line were recruited and included in the study. The median plasma viral load was 77,000 copies/mL [IQR (28,000-290,000)] and the median CD4 cell count was 310 cells/mm [IQR (152-412)]. The median age was 12 years; 48.5% of patients were treated with a combination of stavudine/lamivudine/nevirapine (Triomune) for first-line treatment and 60.6% with abacavir/lamivudine/lopinavir/ritonavir for the second-line ART. The median treatment duration was 8.5 years [range, 3-13]. Of the 33 children whose treatment failed, the predominant HIV-1 subtype was CRF02_AG (66.7%). The prevalence of resistance to ART classes was 60.61% (20/33) to nucleoside reverse transcriptase inhibitors (NRTIs), 54.51% (18/33) to nonnucleoside reverse transcriptase inhibitors (NNRTIs), and 51.52% (17/33) to protease inhibitors (PIs). Of the patients studied, 90.9% were exposed to lopinavir/ritonavir (LPV/r) but only 15.2% (5/33) developed resistance to LPV/r.
This study demonstrated that LPV/r remains active in most patients after second-line ART failure. In children whose second-line ART fails, particular attention should be paid to their ART and adherence history when considering the next treatment option.
近年来，感染艾滋病毒的母亲所生儿童一直在接受抗逆转录病毒治疗（ART），但病毒学监测有限或没有监测，这增加了耐药突变发生和积累的可能性，而耐药突变本身可能会限制未来抗逆转录病毒治疗的效果。本研究的目的是评估在马里加布里埃尔·图雷医院儿科接受二线抗逆转录病毒治疗病毒学失败的艾滋病毒-1感染儿童中耐药突变的流行情况。
纳入年龄在5至18岁、接受二线抗逆转录病毒治疗且在强化观察后病毒载量大于1000拷贝/毫升的艾滋病毒-1感染儿童。使用ViroSeq对蛋白酶和逆转录酶基因进行测序。根据2018年斯坦福算法的最新版本对结果进行解读。该研究获得了巴马科（马里）科学、技术和工艺大学医学与牙科学院伦理委员会的批准。
在216名儿童中，招募了33名（15.3%）二线治疗时病毒载量（VL）>1000拷贝/毫升的儿童并纳入研究。血浆病毒载量中位数为77,000拷贝/毫升[四分位间距（IQR）（28,000 - 290,000）]，CD4细胞计数中位数为310个细胞/立方毫米[IQR（152 - 412）]。中位年龄为12岁；48.5%的患者一线治疗使用司他夫定/拉米夫定/奈韦拉平（三协唯）联合治疗，60.6%的患者二线抗逆转录病毒治疗使用阿巴卡韦/拉米夫定/洛匹那韦/利托那韦。中位治疗持续时间为8.5年[范围，3 - 13年]。在33名治疗失败的儿童中，主要的艾滋病毒-1亚型是CRF02_AG（66.7%）。对各类抗逆转录病毒药物的耐药率分别为：核苷类逆转录酶抑制剂（NRTIs）60.61%（20/33），非核苷类逆转录酶抑制剂（NNRTIs）54.51%（18/33），蛋白酶抑制剂（PIs）51.52%（17/33）。在研究的患者中，90.9%暴露于洛匹那韦/利托那韦（LPV/r），但只有15.2%（5/33）对LPV/r产生耐药。
本研究表明，二线抗逆转录病毒治疗失败后，LPV/r在大多数患者中仍保持活性。对于二线抗逆转录病毒治疗失败的儿童，在考虑下一个治疗方案时，应特别关注他们的抗逆转录病毒治疗情况和依从性历史。
