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危地马拉罗斯福医院临床随访的感染艾滋病毒儿童和青少年中抗逆转录病毒药物获得性耐药的患病率。

Prevalence of acquired resistance to antiretrovirals in children and adolescents living with HIV under clinical follow-up at the Roosevelt Hospital in Guatemala.

作者信息

Alonso S, Salazar E, Gálvez N, Navas J, Quintana C, Orózco N, Prieto L, Navarro M L, Guillén S, Gómez-Alba J M, Medina-Sánchez C, Juarez J, Holguín A

机构信息

Hospital Universitario de Getafe, Madrid 28905, Spain.

Hospital Roosevelt, Ciudad de Guatemala 01011, Guatemala.

出版信息

J Infect Public Health. 2025 Sep;18(9):102827. doi: 10.1016/j.jiph.2025.102827. Epub 2025 May 13.

Abstract

BACKGROUND

Insufficient HIV drug resistance (HIVDR) monitoring in Central America has resulted in widespread circulation of HIV-strains with drug resistance mutations (DRM), compromising antiretroviral therapy (ART). This study aimed to assess the first HIVDR data and DRM patterns in the only HIV-infected pediatric population with resistance information in Guatemala.

METHODS

All HIV-1 infected children and adolescents tested for HIVDR between 2013 and 2021 at Roosevelt Hospital (Guatemala) were retrospectively selected. Their first HIV-1 protease and/or partial retrotranscriptase sequence, when available, was recovered to detect acquired DRMs to three antiretroviral families, and predict resistance to 20 antiretrovirals using the Stanford HIVdb Algorithmv9.5. We compared results with previously recorded DRM data from clinical files. The HIV infecting variant was characterized by phylogeny in those with available sequence.

RESULTS

Ninety-nine children/adolescents were selected, most perinatally-infected (93 %) and without neonatal prophylaxis (92.3 %). The 66 with available sequences harbored HIV-1 subtype B. At first DRM genotyping, all had detectable viral loads (>40cp/ml), 58.6 % experienced virological failure (>1,000cp/ml) despite prior antiretroviral exposure (100 % to NRTI, 77.8 % to NNRTI, 32.3 % to PI and 4 % to INSTI). Most (77.9 %) experienced delayed HIV diagnostic. Half received ART within the first month post-diagnosis. Seventy-nine (79.8%) harbored viruses with DRM: 61 (61.6%) to NRTIs, 70 (70.7%) to NNRTIs and 6 (6.3%) to PIs (major DRMs). Half (52.5 %) presented dual resistance (NRTI+NNRTI) and 5.3 % triple (NRTI+NNRTI+PI). The most frequent DRM to NRTIs were M184V/I/M (47.5 %), to NNRTI K103N/R (48.5 %), and to PIs M46I/L/V (5.3 %). Most (88.4 %) carried PI-susceptible viruses.

CONCLUSION

This study updates HIVDR and HIV-1 variant data in Guatemala, offering the first resistance insights for HIV-infected children and adolescents, showing than PI and INSTI-based regimens may enhance HIV management in this vulnerable pediatric group. Periodic HIVDR monitoring is crucial to control the HIV epidemic in Guatemala.

摘要

背景

中美洲地区对艾滋病毒耐药性(HIVDR)的监测不足,导致携带耐药性突变(DRM)的艾滋病毒毒株广泛传播,影响了抗逆转录病毒疗法(ART)的效果。本研究旨在评估危地马拉唯一有耐药性信息的艾滋病毒感染儿童群体的首批HIVDR数据和DRM模式。

方法

回顾性选取了2013年至2021年期间在危地马拉罗斯福医院接受HIVDR检测的所有HIV-1感染儿童和青少年。若有可用数据,获取他们的首个HIV-1蛋白酶和/或部分逆转录酶序列,以检测对三类抗逆转录病毒药物家族的获得性DRM,并使用斯坦福HIVdb算法v9.5预测对20种抗逆转录病毒药物的耐药性。我们将结果与临床档案中先前记录的DRM数据进行了比较。对有可用序列的患者,通过系统发育分析对感染的艾滋病毒变体进行了特征描述。

结果

选取了99名儿童/青少年,大多数为围产期感染(93%)且未接受新生儿预防措施(92.3%)。66名有可用序列的患者感染的是HIV-1 B亚型。在首次DRM基因分型时,所有人的病毒载量均可检测到(>40拷贝/毫升),58.6%的患者尽管先前接受过抗逆转录病毒治疗(100%接受核苷类逆转录酶抑制剂治疗、77.8%接受非核苷类逆转录酶抑制剂治疗、32.3%接受蛋白酶抑制剂治疗、4%接受整合酶链转移抑制剂治疗),仍出现了病毒学失败(>1000拷贝/毫升)。大多数患者(77.9%)艾滋病毒诊断延迟。一半患者在诊断后第一个月内开始接受抗逆转录病毒治疗。79名(79.8%)患者携带的病毒存在DRM:61名(61.6%)对核苷类逆转录酶抑制剂耐药,70名(70.7%)对非核苷类逆转录酶抑制剂耐药,6名(6.3%)对蛋白酶抑制剂耐药(主要DRM)。一半患者(52.5%)出现双重耐药(核苷类逆转录酶抑制剂+非核苷类逆转录酶抑制剂),5.3%出现三重耐药(核苷类逆转录酶抑制剂+非核苷类逆转录酶抑制剂+蛋白酶抑制剂)。核苷类逆转录酶抑制剂最常见的DRM是M184V/I/M(47.5%),非核苷类逆转录酶抑制剂是K103N/R(48.5%),蛋白酶抑制剂是M46I/L/V(5.3%)。大多数患者(88.4%)携带对蛋白酶抑制剂敏感的病毒。

结论

本研究更新了危地马拉的HIVDR和HIV-1变体数据,为艾滋病毒感染儿童和青少年提供了首个耐药性见解,表明基于蛋白酶抑制剂和整合酶链转移抑制剂的治疗方案可能会改善这一脆弱儿童群体的艾滋病毒管理。定期进行HIVDR监测对于控制危地马拉的艾滋病毒疫情至关重要。

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