Long-term trends in mortality and AIDS-defining events after combination ART initiation among children and adolescents with perinatal HIV infection in 17 middle- and high-income countries in Europe and Thailand: A cohort study.
Long-term trends in mortality and AIDS-defining events after combination ART initiation among children and adolescents with perinatal HIV infection in 17 middle- and high-income countries in Europe and Thailand: A cohort study.
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DOI：
10.1371/journal.pmed.1002491
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发表时间：
2018-01
期刊：
影响因子：
15.8
通讯作者：
Goodall R
中科院分区：
文献类型：
--
作者：
European Pregnancy and Paediatric HIV Cohort Collaboration (EPPICC) study group in EuroCoord;Judd A;Chappell E;Turkova A;Le Coeur S;Noguera-Julian A;Goetghebuer T;Doerholt K;Galli L;Pajkrt D;Marques L;Collins IJ;Gibb DM;González Tome MI;Navarro M;Warszawski J;Königs C;Spoulou V;Prata F;Chiappini E;Naver L;Giaquinto C;Thorne C;Marczynska M;Okhonskaia L;Posfay-Barbe K;Ounchanum P;Techakunakorn P;Kiseleva G;Malyuta R;Volokha A;Ene L;Goodall R
已公布的关于艾滋病毒感染儿童接近成年时的死亡率和发展为艾滋病的估计数是有限的。我们描述了17个中高收入国家（包括西欧和中欧的一些国家）开始联合抗逆转录病毒治疗（cART）后儿童和青少年死亡和艾滋病定义事件的发生率和风险因素（W&CE）、东欧（俄罗斯和乌克兰）和泰国。对开始cART的18岁以下围产期艾滋病毒感染儿童进行随访，直至其21岁生日、转入成人护理、死亡、失访或末次访视，直至2013年12月31日。计算死亡率和首次艾滋病定义事件。评估了早期/晚期（≤/>6个月cART）死亡和进展为AIDS的基线和时间更新的风险因素。在3,526名儿童中，32%来自英国或爱尔兰，30%来自W&CE的其他地方，18%来自俄罗斯或乌克兰，20%来自泰国。在开始cART时，中位年龄为5.2（IQR 1.4-9.3）岁; 1997-2003年，35%的5岁以下儿童的CD 4淋巴细胞百分比<15%，2011年以后降至15%（p < 0.001）。同样，1997-2003年和2011年以后，53%和18%的5岁以上儿童的CD 4计数<200个细胞/mm 3（p < 0.001）。中位随访时间为5.6（2.9-8.7）年。在94例死亡和237例首次艾滋病定义事件中，分别有43例（46%）和100例（42%）发生在开始cART的6个月内。早期死亡的多变量预测因素包括：出生后第一年;居住在俄罗斯、乌克兰或泰国; cART开始时患有艾滋病;开始接受基于非核苷类逆转录酶抑制剂（NNRTI）的cART治疗方案;严重免疫抑制;年龄别BMI z评分较低。当前严重的免疫抑制，低的当前BMI-年龄z-评分，和当前病毒载量>400 c/mL预测晚期死亡。早期和晚期进展为艾滋病的预测因素相似。研究局限性包括美国疾病控制中心（CDC）疾病B期事件和一些国家的严重不良事件记录不完整;事件分布在很长一段时间内，我们缺乏分析死亡模式和原因随时间变化趋势的能力。在我们的研究中，3,526名围产期感染艾滋病毒的儿童和青少年在欧洲和泰国开始了抗逆转录病毒治疗（ART）。我们观察到超过40%的死亡发生在cART启动后≤6个月。与年龄较大的儿童相比，婴儿的早期死亡风险更大，与W&CE相比，俄罗斯，乌克兰或泰国的风险更大，引起了人们的关注。目前严重的免疫抑制、体重不足和未抑制的病毒载量与开始cART后>6个月的死亡风险较高相关。在一项多国队列研究中，Ali Judd及其同事研究了接受抗逆转录病毒治疗的艾滋病毒感染儿童和青少年的发病率、死亡率和相关风险因素。各种利益攸关方都强调，青少年是全球卫生方面的一个紧迫优先事项。艾滋病毒/艾滋病是全球青少年十大死亡原因之一。对儿童接近成年时的死亡率和发展为艾滋病的估计是有限的。我们调查了西欧和中欧、东欧（俄罗斯、乌克兰）和泰国高收入和中等收入国家中围产期感染艾滋病毒的儿童和青少年的长期死亡风险和艾滋病定义事件。在我们的研究中，来自17个国家的3，526例患者中，开始cART治疗时的中位年龄为5.2岁，中位随访持续时间为5.6年，年龄≥10岁的患者随访9，228人-年，总体随访20，574人-年。我们发现，在东欧国家和泰国，以及目前严重免疫抑制和低BMI的患者中，非常年幼的儿童死亡风险较高。我们描述了一些第一代儿童围产期艾滋病毒生存和达到青春期的结果。我们的研究结果以及其他现有证据表明，需要对感染艾滋病毒的幼儿、严重免疫抑制儿童以及BMI低于其年龄预期的儿童进行持续的强化监测。
Published estimates of mortality and progression to AIDS as children with HIV approach adulthood are limited. We describe rates and risk factors for death and AIDS-defining events in children and adolescents after initiation of combination antiretroviral therapy (cART) in 17 middle- and high-income countries, including some in Western and Central Europe (W&CE), Eastern Europe (Russia and Ukraine), and Thailand. Children with perinatal HIV aged <18 years initiating cART were followed until their 21st birthday, transfer to adult care, death, loss to follow-up, or last visit up until 31 December 2013. Rates of death and first AIDS-defining events were calculated. Baseline and time-updated risk factors for early/late (≤/>6 months of cART) death and progression to AIDS were assessed. Of 3,526 children included, 32% were from the United Kingdom or Ireland, 30% from elsewhere in W&CE, 18% from Russia or Ukraine, and 20% from Thailand. At cART initiation, median age was 5.2 (IQR 1.4–9.3) years; 35% of children aged <5 years had a CD4 lymphocyte percentage <15% in 1997–2003, which fell to 15% of children in 2011 onwards (p < 0.001). Similarly, 53% and 18% of children ≥5 years had a CD4 count <200 cells/mm3 in 1997–2003 and in 2011 onwards, respectively (p < 0.001). Median follow-up was 5.6 (2.9–8.7) years. Of 94 deaths and 237 first AIDS-defining events, 43 (46%) and 100 (42%) were within 6 months of initiating cART, respectively. Multivariable predictors of early death were: being in the first year of life; residence in Russia, Ukraine, or Thailand; AIDS at cART start; initiating cART on a nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimen; severe immune suppression; and low BMI-for-age z-score. Current severe immune suppression, low current BMI-for-age z-score, and current viral load >400 c/mL predicted late death. Predictors of early and late progression to AIDS were similar. Study limitations include incomplete recording of US Centers for Disease Control (CDC) disease stage B events and serious adverse events in some countries; events that were distributed over a long time period, and that we lacked power to analyse trends in patterns and causes of death over time. In our study, 3,526 children and adolescents with perinatal HIV infection initiated antiretroviral therapy (ART) in countries in Europe and Thailand. We observed that over 40% of deaths occurred ≤6 months after cART initiation. Greater early mortality risk in infants, as compared to older children, and in Russia, Ukraine, or Thailand as compared to W&CE, raises concern. Current severe immune suppression, being underweight, and unsuppressed viral load were associated with a higher risk of death at >6 months after initiation of cART. In a multi-country cohort study, Ali Judd and colleagues study morbidity, mortality, and relevant risk factors in children and adolescents with HIV infection receiving antiretroviral treatment. Adolescence has been highlighted as an urgent global priority for health by a diverse range of stakeholders. HIV/AIDS is one of the top 10 leading causes of death in adolescents globally. Estimates of mortality and progression to AIDS as children approach adulthood are limited. We investigated long-term risk of death and AIDS-defining events in children and adolescents with perinatal HIV across high- and middle-income country settings in Western and Central Europe, Eastern Europe (Russia, Ukraine), and Thailand. In our study, in 3,526 patients across 17 countries, median age at cART initiation was 5.2 years, and median duration of follow-up was 5.6 years, with 9,228 person-years of follow-up in those aged ≥10 years and 20,574 person-years overall. We found that there was a higher risk of mortality in very young children, in Eastern European countries and Thailand, and in patients with current severe immune suppression and low BMI. We describe outcomes for some of the first generation of children to survive perinatal HIV and reach adolescence. Our findings, together with other available evidence, suggest an ongoing need for intensive monitoring of very young children with HIV infection, those with severe immunosuppression, and those with a lower BMI than that expected for their age.
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影响因子：
3
作者：
Bamford A;Turkova A;Lyall H;Foster C;Klein N;Bastiaans D;Burger D;Bernadi S;Butler K;Chiappini E;Clayden P;Della Negra M;Giacomet V;Giaquinto C;Gibb D;Galli L;Hainaut M;Koros M;Marques L;Nastouli E;Niehues T;Noguera-Julian A;Rojo P;Rudin C;Scherpbier HJ;Tudor-Williams G;Welch SB;(PENTA Steering Committee)
通讯作者：
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DOI：
10.1097/qai.0b013e318207a55b
发表时间：
2011-04-01
影响因子：
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DOI：
10.1097/qai.0b013e3181e0c4cf
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2010-08
期刊：
Journal of acquired immune deficiency syndromes (1999)
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