Pediatr Infect Dis J. 2018 Mar;37(3):e48-e57. doi: 10.1097/INF.0000000000001760.
The expanded use of long-term antiretroviral treatments in infected children may exacerbate the problem of drug resistance mutations selection, which can compromise treatment efficiency.
We describe the temporal trends of HIV drug resistance mutations and the HIV-1 variants during 23 years (1993 to March 2016) in the Madrid cohort of HIV-infected children and adolescents.
We selected patients with at least one available HIV-1 pol sequence/genotypic resistance profile, establishing different groups according to the sampling year of first resistance data. We determined the prevalence of transmitted drug resistance mutations or acquired drug resistance mutations (DRM), the drug susceptibility among resistant viruses and HIV-1 variants characterized by phylogeny across time.
A total of 245 pediatric patients were selected, being mainly female, Spanish native, perinatally infected and carrying HIV-1 subtype B. At first sampling, most pediatric patients were on antiretroviral therapy and heavily pretreated. During 1993 to 2016, transmitted drug resistance mutations was found in 13 (26%) of 50 naive children [non-nucleoside reverse transcriptase inhibitors (NNRTI), 14.6%; nucleoside reverse transcriptase inhibitors (NRTI), 10.4%; protease inhibitors, 8.7%]. DRM appeared in 139 (73.2%) of 190 pretreated patients (NRTI, 64.5%; NNRTI, 36%; protease inhibitors, 35.1%). DRM to NNRTI was higher in last 5 years. Non-B variants infected 14.5% of children and adolescents of the Madrid Cohort, being mainly intersubtype recombinants (76.5%), including complex unique recombinant strains. They caused 3.4% infections before 2000, rising to 85.7% during 2011 to 2016.
Periodic surveillance resistance and molecular epidemiology studies in long-term pretreated HIV-infected pediatric populations are required to optimize treatment regimens. Results will permit a better understanding of long-time dynamics of viral resistance and HIV-1 variants in Spain.
长期抗逆转录病毒治疗在感染儿童中的广泛应用可能会加剧耐药突变选择的问题，从而降低治疗效率。
我们描述了 23 年来（1993 年至 2016 年 3 月）马德里 HIV 感染儿童和青少年队列中 HIV 耐药突变和 HIV-1 变异体的时间趋势。
我们选择了至少有一个可用的 HIV-1 pol 序列/基因型耐药谱的患者，根据首次耐药数据的采样年份建立了不同的组。我们确定了传播耐药突变或获得性耐药突变（DRM）的流行率、耐药病毒的药物敏感性以及通过系统发育随时间变化的 HIV-1 变异体。
共选择了 245 名儿科患者，主要为女性、西班牙本地人、围产期感染和携带 HIV-1 亚型 B。在首次采样时，大多数儿科患者正在接受抗逆转录病毒治疗且已进行了大量的前期治疗。1993 年至 2016 年期间，在 50 名未接受过治疗的儿童中发现了 13 例（26%）传播耐药突变[非核苷类逆转录酶抑制剂（NNRTI），14.6%；核苷类逆转录酶抑制剂（NRTI），10.4%；蛋白酶抑制剂，8.7%]。在 190 名接受过前期治疗的患者中出现了 139 例（73.2%）获得性耐药突变（NRTI，64.5%；NNRTI，36%；蛋白酶抑制剂，35.1%）。最后 5 年，NNRTI 耐药突变率较高。马德里队列中有 14.5%的儿童和青少年感染了非 B 型变异体，主要是亚型间重组（76.5%），包括复杂的独特重组株。它们在 2000 年前导致了 3.4%的感染，在 2011 年至 2016 年期间上升至 85.7%。
需要对长期接受前期治疗的 HIV 感染儿科人群进行定期耐药监测和分子流行病学研究，以优化治疗方案。研究结果将有助于更好地了解西班牙病毒耐药和 HIV-1 变异体的长期动态。
