Medical Research Council, Clinical Trials Unit, London, UK.
Curr Opin HIV AIDS. 2012 Jul;7(4):305-16. doi: 10.1097/COH.0b013e328354da1d.
Antiretroviral therapy (ART) has greatly improved the survival of HIV-infected children. However, ART is associated with immediate and long-term adverse events. Pharmacovigilance systems, although imperfect, have been developed in many high-income countries (HICs), but coverage in low- and middle-income countries (LMICs) is poor and uneven. This review covers the recent advances in the understanding of adverse events following perinatal ART exposure, including surveillance from birth cohorts; we also describe the adverse events of antiretroviral drugs among HIV-infected children, focussing particularly on those relevant to LMICs, where more than 90% of HIV-infected children live.
ART is largely safe in both HIV-infected and HIV-exposed uninfected children, in whom no significant increase in birth defects has been noted. Among HIV-infected children, toxicity to some drugs may be less frequent than in adults, possibly related to immature immune systems in younger children. As per WHO guidelines, many countries are moving from stavudine-based to zidovudine-based or abacavir-based fixed-dose combination (with nevirapine/lamivudine) paediatric mini-pills. However, reassuring data are emerging about short-term stavudine use in LMICs, as this remains an important first-line regimen for young children, as well as an alternative to zidovudine for anaemic children. Zidovudine appears to be well tolerated in young children living in nonmalarious areas, and, among African children, concerns about abacavir hypersensitivity have not been substantiated.
Optimization of first-line ART regimens needs to take account of the toxicities in HIV-infected children, in particular as they will take ART much longer than adults and during the period of growth and development. The benefits of ART in pregnancy are clear, but long-term follow-up of ART-exposed infants in LMICs through integrated surveillance systems would be invaluable.
抗逆转录病毒疗法（ART）极大地提高了 HIV 感染儿童的生存率。然而，ART 与即刻和长期不良事件相关。尽管不完善，但许多高收入国家（HICs）已经开发了药物警戒系统，但中低收入国家（LMICs）的覆盖率较差且不均衡。本综述涵盖了围产期接受 ART 后不良事件的最新认识，包括从出生队列进行的监测；我们还描述了 HIV 感染儿童的抗逆转录病毒药物的不良事件，特别关注与 90%以上 HIV 感染儿童生活的 LMICs 相关的不良事件。
在 HIV 感染和 HIV 暴露未感染儿童中，ART 基本安全，未发现明显增加出生缺陷。在 HIV 感染儿童中，一些药物的毒性可能不如成人常见，这可能与年幼儿童不成熟的免疫系统有关。根据世界卫生组织的指南，许多国家正在从基于司他夫定的方案转向基于齐多夫定或阿巴卡韦的固定剂量联合（与奈韦拉平/拉米夫定）儿科迷你丸。然而，在 LMICs 中短期使用司他夫定的令人放心的数据正在出现，因为这仍然是年幼儿童的重要一线方案，也是儿童贫血时替代齐多夫定的方案。齐多夫定在无疟疾地区的幼儿中似乎耐受性良好，在非洲儿童中，对阿巴卡韦过敏的担忧并未得到证实。
需要考虑到 HIV 感染儿童的毒性来优化一线 ART 方案，特别是因为他们将比成人更长时间接受 ART，并且处于生长和发育阶段。ART 在妊娠中的益处是明确的，但通过综合监测系统对 LMICs 中接受 ART 的婴儿进行长期随访将是非常宝贵的。
