Duke Human Vaccine Institute, Duke University School of Medicine, 2 Genome Court MSRBII, Durham, NC, 27710, USA.
Johns Hopkins University School of Medicine, 720 Rutland Avenue, Ross Building 1170, Baltimore, MD, 21205, USA.
Curr HIV/AIDS Rep. 2020 Jun;17(3):237-248. doi: 10.1007/s11904-020-00495-1.
In the absence of antiretroviral therapy (ART), more than 50% of perinatally HIV-infected children die by 2 years of age. Early ART from infancy is therefore a global recommendation and significantly improves immune health, child survival, and disease outcome. However, even early treatment does not prevent or eradicate the latent reservoir necessitating life-long ART. Adherence to life-long ART is challenging for children and longstanding ART during chronic HIV infection led to higher risks of non-AIDS co-morbidities and virologic failure in infected children. Thus, HIV-infected children are an important population for consideration for immune-based interventions to achieve ART-free remission and functional cure. This review summarizes how the uniqueness of the early life immune system can be harnessed for the development of ART-free remission and functional cure, which means complete virus control in absence of ART. In addition, recent advances in therapeutics in the HIV cure field and their potential for the treatment of pediatric HIV infections are discussed.
Preclinical studies and clinical trials demonstrated that immune-based interventions target HIV replication, limit size of virus reservoir, maintain virus suppression, and delay time to virus rebound. However, these studies have been performed so far only in carefully selected HIV-infected adults, highlighting the need to evaluate the efficacy of immune-based therapeutics in HIV-infected children and to design interventions tailored to the early life maturing immune system. Immune-based therapeutics alone or in combination with ART should be actively explored as potential strategies to achieve viral remission and functional cure in HIV-infected pediatric populations.
在没有抗逆转录病毒疗法 (ART) 的情况下，超过 50%的围产期感染 HIV 的儿童在 2 岁前死亡。因此，婴儿早期开始 ART 是全球的推荐方案，可显著改善免疫健康、儿童存活率和疾病结局。然而，即使早期治疗也不能预防或消除潜伏的病毒库，从而需要终生接受 ART。儿童坚持终生接受 ART 存在挑战，长期接受慢性 HIV 感染期间的 ART 会导致非艾滋病合并症和病毒学失败的风险增加。因此，HIV 感染的儿童是考虑免疫干预以实现无 ART 缓解和功能性治愈的重要人群。本文综述了如何利用早期生命免疫系统的独特性来开发无 ART 缓解和功能性治愈，即无需 ART 即可实现完全病毒控制。此外，还讨论了 HIV 治愈领域的治疗学最新进展及其在儿科 HIV 感染治疗中的潜在应用。
临床前研究和临床试验表明，免疫干预可靶向 HIV 复制、限制病毒库大小、维持病毒抑制并延迟病毒反弹时间。然而，到目前为止，这些研究仅在经过精心挑选的 HIV 感染成人中进行，这突出表明需要评估免疫治疗在 HIV 感染儿童中的疗效，并设计针对早期生命成熟免疫系统的干预措施。单独使用免疫治疗或与 ART 联合使用应积极探索作为实现 HIV 感染儿科人群病毒缓解和功能性治愈的潜在策略。
