The promise of paediatric dolutegravir.
The promise of paediatric dolutegravir.
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DOI：
10.1002/jia2.25660
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发表时间：
2021-01
影响因子：
6
通讯作者：
Siberry GK
中科院分区：
文献类型：
--
作者：
Golin R;Samuel JM;Phelps BR;Persaud U;Malati CY;Siberry GK
2019年，估计有180万艾滋病毒感染儿童（CLHIV）中，只有不到55%接受了挽救生命的抗逆转录病毒治疗（ART）[1]。低收入和中等收入国家（LMIC）的儿童获得最佳儿科ART的机会仍然有限[2]，儿童中的病毒载量抑制（VLS）率仍然低得令人无法接受[3]。为了到2030年实现联合国艾滋病规划署为所有年龄段制定的95-95-95基准[4]，LMIC迫切需要获得强大的，负担得起的和儿童友好的儿科ART方案[2]。自2018年以来，世界卫生组织（WHO）建议使用dolutegravir（DTG），一种整合酶链转移抑制剂，作为所有艾滋病毒感染者（PLHIV）首选的一线ART方案的一部分，其中有批准和可用的剂量[5]。然而，迄今为止，DTG仅以50 mg薄膜包衣片剂的形式在LMIC中可用，该制剂仅可用于体重至少20 kg的儿童[5]。2020年6月，美国食品和药物管理局（US FDA）批准DTG的5 mg分散制剂用于感染艾滋病毒的婴儿和儿童[6]，并于2020年11月，儿科DTG 10 mg刻痕分散片制剂（DTG 10）也获得了美国FDA的初步批准[7]。有了这些批准，LMIC有望在2021年获得通用DTG 10 [8]。DTG分散片的引入是CLHIV最佳治疗的重大进展。根据从成人研究中推断的数据，DTG的疗效上级蛋白酶抑制剂（PI）[9]和非核苷逆转录酶抑制剂（NNRTI）[10]。DTG的引入直接解决了CLHIV中的治疗前耐药性[11]以及基于NNRTI或PI的方案失败后的获得性耐药性[8]。此外，由于耐药性的高遗传屏障，DTG可与优化的NRTI骨架一起沿着使用，作为整个儿童期和成年期的锚药物[8]。这在基因型耐药性测试非常有限的LMIC中尤其重要[12]。儿科DTG也是一种方便的每日一次分散片制剂，可与ABC/3 TC分散制剂一起溶解和给药[6，8]。
In 2019, fewer than 55% of the estimated 1.8 million children living with HIV (CLHIV) received life-saving antiretroviral therapy (ART)[1]. Children in low-and middle-income countries (LMIC) continue to have limited access to optimal paediatric ART [2], and viral load suppression (VLS) rates among children remain unacceptably low [3]. To achieve the UNAIDS 95-95-95 benchmarks for all ages by 2030 [4], there is a pressing need for LMIC to have access to robust, affordable and childfriendly paediatric ART regimens [2]. Since 2018, the World Health Organization (WHO) has recommended the use of dolutegravir (DTG), an integrase strand transfer inhibitor, as part of the preferred first-line ART regimen for all people living with HIV (PLHIV) for whom there is approved and available dosing [5]. However, to date, DTG has only been available in LMIC as a 50 mg, film-coated tablet, a formulation that can only be used by children who weigh at least 20 kg [5].In June 2020, the United States Food and Drug Administration (US FDA) approved a dispersible, 5 mg formulation of DTG for use in infants and children living with HIV [6], and in November 2020, a paediatric DTG 10 mg scored disperisble tablet formulation (DTG10) also received tentative US FDA approval [7]. With these approvals in place, LMIC can expect to have access to generic DTG10 available in 2021 [8]. The introduction of a DTG dispersible tablet is a significant advance in optimal treatment for CLHIV. Based on data extrapolated from studies in adults, DTG’s efficacy is superior to both protease inhibitors (PIs)[9] and non-nucleoside reverse transcriptase inhibitors (NNRTIs)[10]. Introduction of DTG directly addresses pre-treatment drug resistance among CLHIV [11] as well as acquired drug resistance after failed NNRTI-or PI-based regimens [8]. Additionally, due to a high genetic barrier to resistance, DTG can be used along with an optimized NRTI backbone as an anchor drug throughout childhood and adulthood [8]. This is especially critical in LMIC where genotypic drug resistance testing is very limited [12]. Paediatric DTG also comes in a convenient, once-daily, dispersible tablet formulation that can be dissolved and administered alongside dispersible formulations of ABC/3TC [6, 8].
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影响因子：
5
作者：
Brenner, Bluma G.;Wainberg, Mark A.
通讯作者：
Wainberg, Mark A.
影响因子：
6
作者：
Malati, Christine Y.;Golin, Rachel;Phelps, Benjamin R.
通讯作者：
Phelps, Benjamin R.
DOI：
10.1097/qai.0000000000001747
发表时间：
2018-08-15
期刊：
Journal of acquired immune deficiency syndromes (1999)
影响因子：
--
作者：
Abrams EJ;Ananworanich J;Archary M;Ngongondo M;Brouwers P
通讯作者：
Brouwers P
影响因子：
16.1
作者：
Molina, Jean-Michel;Clotet, Bonaventura;Brennan, Clare
通讯作者：
Brennan, Clare