Development of HIV drug resistance and therapeutic failure in children and adolescents in rural Tanzania: an emerging public health concern.
Development of HIV drug resistance and therapeutic failure in children and adolescents in rural Tanzania: an emerging public health concern.
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DOI：
10.1097/qad.0000000000001273
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发表时间：
2017-01-02
期刊：
影响因子：
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通讯作者：
KIULARCO Study Group
中科院分区：
文献类型：
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作者：
Muri L;Gamell A;Ntamatungiro AJ;Glass TR;Luwanda LB;Battegay M;Furrer H;Hatz C;Tanner M;Felger I;Klimkait T;Letang E;KIULARCO Study Group
调查坦桑尼亚农村艾滋病毒感染儿童和青少年病毒学失败和获得性耐药相关突变（DRMs）的患病率和决定因素。前瞻性队列研究与横断面分析。所有在Ifakara儿科艾滋病毒诊所就诊并接受抗逆转录病毒治疗（ART）至少12个月的18岁或以下儿童均被纳入研究。对病毒学失败的参与者进行HIV-DRM检测。使用抗逆转录病毒治疗前的样本来区分获得性和传播性耐药性。多变量逻辑回归分析确定了与病毒学失败和HIV-DRM获得相关的因素。在接受抗逆转录病毒治疗的213名儿童中，平均4.3年，25.4%的儿童病毒学失败。与art相关的DRM鉴定率为90%，多级别耐药率为79%。抗逆转录病毒治疗前的数据表明，85%以上的人在治疗期间获得了关键突变。次优依从性[比值比(OR) = 3.90；95%可信区间（CI） 1.11-13.68]、女性（aOR = 2.57; 95% CI 1.03-6.45）和目前基于非核苷类逆转录酶抑制剂的ART （aOR = 7.32; 95% CI 1.51-35.46，与基于蛋白酶抑制剂的ART相比）分别增加了病毒学失败的几率。CD4+ t细胞百分比（aOR = 0.20；每增加10% 0.10-0.40）和ART开始时年龄较大（aOR = 0.84 /每增加一岁；95% CI 0.73-0.97）具有保护作用（也可预测获得性HIV-DRM）。在病毒学失败时，不到5%的儿童符合世卫组织的免疫失败标准。儿童和青少年的病毒学失败率很高，大多数抗逆转录病毒治疗失败的儿童携带HIV-DRM。世卫组织免疫治疗失败标准的敏感性低得令人无法接受。迫切需要进行病毒载量监测，以便为数百万感染艾滋病毒的非洲儿童提供未来的治疗选择。
To investigate the prevalence and determinants of virologic failure and acquired drug resistance-associated mutations (DRMs) in HIV-infected children and adolescents in rural Tanzania. Prospective cohort study with cross-sectional analysis. All children 18 years or less attending the paediatric HIV Clinic of Ifakara and on antiretroviral therapy (ART) for at least 12 months were enrolled. Participants with virologic failure were tested for HIV-DRM. Pre-ART samples were used to discriminate acquired and transmitted resistances. Multivariate logistic regression analysis identified factors associated with virologic failure and the acquisition of HIV-DRM. Among 213 children on ART for a median of 4.3 years, 25.4% failed virologically. ART-associated DRM were identified in 90%, with multiclass resistances in 79%. Pre-ART data suggested that more than 85% had acquired key mutations during treatment. Suboptimal adherence [odds ratio (OR) = 3.90; 95% confidence interval (CI) 1.11–13.68], female sex (aOR = 2.57; 95% CI 1.03–6.45), and current nonnucleoside reverse transcriptase inhibitor-based ART (aOR = 7.32; 95% CI 1.51–35.46 compared with protease inhibitor-based) independently increased the odds of virologic failure. CD4+ T-cell percentage (aOR = 0.20; 0.10–0.40 per additional 10%) and older age at ART initiation (aOR = 0.84 per additional year of age; 95% CI 0.73–0.97) were protective (also in predicting acquired HIV-DRM). At the time of virologic failure, less than 5% of the children fulfilled the WHO criteria for immunologic failure. Virologic failure rates in children and adolescents were high, with the majority of ART-failing children harbouring HIV-DRM. The WHO criteria for immunologic treatment failure yielded an unacceptably low sensitivity. Viral load monitoring is urgently needed to maintain future treatment options for the millions of African children living with HIV.