Ananworanich Jintanat, Puthanakit Thanyawee, Suntarattiwong Piyarat, Chokephaibulkit Kulkanya, Kerr Stephen J, Fromentin Rémi, Bakeman Wendy, Intasan Jintana, Mahanontharit Apicha, Sirivichayakul Sunee, Chomont Nicolas
aThe HIV Netherlands Australia Thailand Research Collaboration bSEARCH, The Thai Red Cross AIDS Research Center cFaculty of Medicine, Department of Medicine dFaculty of Medicine, Department of Pediatrics, Chulalongkorn University eQueen Sirikit National Institute of Child Health fFaculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand gKirby Institute of Infection and Immunity in Society, The University of New South Wales, Sydney, Australia hVaccine and Gene Therapy Institute of Florida, Port St Lucie, Florida, USA.
AIDS. 2014 Apr 24;28(7):1015-20. doi: 10.1097/QAD.0000000000000178.
Understanding the extent to which early antiretroviral therapy (ART) can limit the establishment and persistence of the HIV reservoir is an important step to designing interventions aimed at achieving HIV cure. We measured the markers of HIV persistence and HIV-specific immunity in early treated children.
This is a cross-sectional study that enrolled 15 children older than 2 years of age who initiated ART before 6 months of age and had sustained viral suppression. Total and integrated HIV DNA, and 2-LTR circles in CD4 T cells, HIV antibody response by fourth generation HIV enzyme immunoassay, and CD4 and CD8 T-cell responses to gag/env peptides by intracellular cytokine staining of CD4 and CD8 T cells were measured.
The median current age was 6.3 years and age at ART initiation was 17 weeks. The median duration of viral suppression was 6 years, and all had HIV RNA less than 50 copies/ml. The median CD4 T cells was 44%. The median total HIV DNA was 132 copies/10 CD4 T cells (range 11-1804) and integrated HIV DNA was 17 copies/10 CD4 T cells (range 0-516), and no one had detectable 2-LTR circles. Nine of the 15 children (60%) had undetectable or extremely low integrated HIV DNA (<20 copies/10 CD4 T cells). All except one (93%) had undetectable HIV-specific CD4/CD8 cell responses and seven (47%) had nonreactive enzyme immunoassay.
Early ART resulted in very low levels of markers of HIV persistence and undetectable HIV-specific immune responses in the majority of HIV-infected children who started ART before 6 months of age.
了解早期抗逆转录病毒疗法(ART)能在多大程度上限制HIV储存库的建立和持续存在,是设计旨在实现HIV治愈的干预措施的重要一步。我们测量了早期接受治疗的儿童中HIV持续存在的标志物和HIV特异性免疫。
这是一项横断面研究,纳入了15名2岁以上在6个月龄前开始接受ART且病毒得到持续抑制的儿童。测量了CD4 T细胞中的总HIV DNA和整合HIV DNA、2-LTR环,通过第四代HIV酶免疫测定法检测HIV抗体反应,以及通过CD4和CD8 T细胞的细胞内细胞因子染色检测CD4和CD8 T细胞对gag/env肽的反应。
当前年龄中位数为6.3岁,开始接受ART时的年龄为17周。病毒抑制的中位数持续时间为6年,所有儿童的HIV RNA均低于50拷贝/毫升。CD4 T细胞中位数为44%。总HIV DNA中位数为132拷贝/10个CD4 T细胞(范围为11 - 1804),整合HIV DNA为17拷贝/10个CD4 T细胞(范围为0 - 516),没有人检测到2-LTR环。15名儿童中有9名(60%)的整合HIV DNA检测不到或极低(<20拷贝/10个CD4 T细胞)。除1名儿童外,所有儿童(93%)的HIV特异性CD4/CD8细胞反应检测不到,7名儿童(47%)的酶免疫测定无反应。
早期ART导致大多数在6个月龄前开始接受ART的HIV感染儿童中HIV持续存在的标志物水平非常低,且HIV特异性免疫反应检测不到。