Rogo Tanya, DeLong Allison K, Chan Philip, Kantor Rami
Department of Pediatrics.
Center for Statistical Sciences.
Clin Infect Dis. 2015 May 1;60(9):1426-35. doi: 10.1093/cid/civ058. Epub 2015 Jan 30.
Drug resistance development in the human immunodeficiency virus (HIV)-infected pediatric population in the United States can impact long-term antiretroviral therapy (ART) efficacy. Limited formularies and adherence constraints in children jeopardize lifelong-needed ART.
We examined treatment failure, drug resistance, and their correlates in ART-naive and ART-experienced children attending the pediatric HIV clinic in Rhode Island between 1991 and 2012. Pol sequences were obtained for phylogenetic, subtype, and resistance analyses. Associations between selected covariates and virologic failure and resistance were evaluated using generalized additive models and Fisher exact tests.
Data were available for all 56 clinic-attending children. At diagnosis, 33% were aged <1 year, 31% aged 1-4 years, and 37% aged ≥ 5 years; 54% were male, 73% black or Hispanic, 55% US-born, 20% refugees, and 64% perinatally infected. Of 44 ART-experienced children, 57% had virologic failure, most never virologically suppressed. Failure was associated with missed appointments (P = .05) and missed doses (P < .01). Of 40 children with available genotypes, 35% were infected with non-B subtypes; 6% of ART-naive children had resistance; and 73% of ART-experienced children had ≥ 1 major mutation: (16% conferring triple-class, 47% dual-class, and 37% single-class resistance). An epidemiologically confirmed resistance transmission from a perinatally infected teenage male to a newly infected teenage female was demonstrated.
We report high HIV type 1 diversity, extensive drug resistance among ART-experienced children, and horizontal transmission of resistance in the Rh ode Island pediatric HIV clinic. As HIV-infected children mature into adulthood, close monitoring of ART, adherence, and diagnosis disclosure are essential to optimize patient care.
美国感染人类免疫缺陷病毒(HIV)的儿童群体中耐药性的产生会影响长期抗逆转录病毒疗法(ART)的疗效。儿童有限的药物配方和依从性限制危及了终身所需的抗逆转录病毒疗法。
我们调查了1991年至2012年间在罗德岛儿科HIV诊所接受治疗的初治和经治儿童的治疗失败、耐药性及其相关因素。获取pol序列用于系统发育、亚型和耐药性分析。使用广义相加模型和Fisher精确检验评估选定协变量与病毒学失败和耐药性之间的关联。
所有56名就诊儿童的数据均可用。诊断时,33%的儿童年龄小于1岁,31%的儿童年龄在1至4岁之间,37%的儿童年龄大于或等于5岁;54%为男性,73%为黑人或西班牙裔,55%在美国出生,20%为难民,64%为围产期感染。在44名经治儿童中,57%出现病毒学失败,大多数从未实现病毒学抑制。治疗失败与错过预约(P = 0.05)和漏服剂量(P < 0.01)有关。在40名有可用基因型的儿童中,35%感染了非B亚型;6%的初治儿童有耐药性;73%的经治儿童有≥1个主要突变:(16%导致三类耐药,47%导致二类耐药,37%导致一类耐药)。证实了从一名围产期感染的青少年男性到一名新感染的青少年女性的耐药性传播,经流行病学确认。
我们报告了罗德岛儿科HIV诊所中1型HIV的高度多样性、经治儿童中的广泛耐药性以及耐药性的水平传播。随着感染HIV的儿童成长为成年人,密切监测抗逆转录病毒疗法、依从性和诊断披露对于优化患者护理至关重要。