Persaud Deborah, Patel Kunjal, Karalius Brad, Rainwater-Lovett Kaitlin, Ziemniak Carrie, Ellis Angela, Chen Ya Hui, Richman Douglas, Siberry George K, Van Dyke Russell B, Burchett Sandra, Seage George R, Luzuriaga Katherine
Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Department of Epidemiology and the Center for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, Massachusetts.
JAMA Pediatr. 2014 Dec;168(12):1138-46. doi: 10.1001/jamapediatrics.2014.1560.
Combination antiretroviral therapy initiated within several weeks of human immunodeficiency virus (HIV) infection in adults limits proviral reservoirs that preclude HIV cure. Biomarkers of restricted proviral reservoirs may aid in the monitoring of HIV remission or cure.
To quantify peripheral blood proviral reservoir size in perinatally HIV-infected (PHIV+) adolescents and to identify correlates of limited proviral reservoirs.
DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional study including 144 PHIV+ youths (median age, 14.3 years) enrolled in the United States-based Pediatric HIV/AIDS Cohort Study and receiving durable (median duration, 10.2 years) combination antiretroviral therapy, stratified by age at virologic control.
The primary end point was peripheral blood mononuclear cell (PBMC) proviral load after virologic control at different ages. Correlations between proviral load and markers of active HIV production (ie, HIV-specific antibodies, 2-long terminal repeat circles) and markers of immune activation and inflammation were also assessed.
Proviral reservoir size was markedly reduced in the PHIV+ youth who achieved virologic control before 1 year of age (4.2 [interquartile range, 2.6-8.6] copies per 1 million PBMCs) compared with those who achieved virologic control at 1 to 5 years of age (19.4 [interquartile range, 5.5-99.8] copies per 1 million PBMCs) or after 5 years of age (70.7 [interquartile range, 23.2-209.4] copies per 1 million PBMCs; P < .001). A proviral burden of less than 10 copies per 1 million PBMCs in PHIV+ youth was measured in 11 (79%), 20 (40%), and 13 (18%) participants with virologic control before 1 year, at 1 to 5 years, and after 5 years of age, respectively (P < .001). Lower proviral load was associated with undetectable 2-long terminal repeat circles (P < .001) and HIV-negative or indeterminate serostatus (P < .001) but not with concentrations of soluble immune activation markers CD14 and CD163.
Early effective combination antiretroviral therapy with prolonged virologic suppression after perinatal HIV infection leads to negligible peripheral blood proviral reservoirs in adolescence and is associated with negative or indeterminate HIV serostatus. These findings highlight the long-term effect of early effective control of HIV replication on biomarkers of HIV persistence in perinatal infection and the utility of HIV serostatus as a biomarker for small proviral reservoir size, although not necessarily for cure.
在成人感染人类免疫缺陷病毒（HIV）数周内启动的联合抗逆转录病毒疗法可限制前病毒储存库，而这是实现HIV治愈的障碍。受限的前病毒储存库生物标志物可能有助于监测HIV缓解或治愈情况。
量化围产期感染HIV（PHIV+）青少年的外周血前病毒储存库大小，并确定前病毒储存库受限的相关因素。
设计、地点和参与者：一项横断面研究，纳入了144名PHIV+青少年（中位年龄14.3岁），他们参与了美国的儿科HIV/艾滋病队列研究，接受了长期（中位持续时间10.2年）联合抗逆转录病毒疗法，并按病毒学控制时的年龄分层。
主要终点是不同年龄病毒学控制后的外周血单个核细胞（PBMC）前病毒载量。还评估了前病毒载量与活跃HIV产生标志物（即HIV特异性抗体、2-长末端重复序列环）以及免疫激活和炎症标志物之间的相关性。
与1至5岁实现病毒学控制的青少年（每100万个PBMC中有19.4[四分位间距，5.5-99.8]拷贝）或5岁后实现病毒学控制的青少年（每100万个PBMC中有70.7[四分位间距，23.2-209.4]拷贝；P < .001）相比，1岁前实现病毒学控制的PHIV+青少年的前病毒储存库大小显著降低（每100万个PBMC中有4.2[四分位间距，2.6-8.6]拷贝）。在1岁前、1至5岁和5岁后实现病毒学控制的参与者中，分别有11名（79%）、20名（40%）和13名（18%）的PHIV+青少年每100万个PBMC中的前病毒负担低于10拷贝（P < .001）。较低的前病毒载量与无法检测到的2-长末端重复序列环（P < .001）和HIV阴性或不确定血清学状态（P < .001）相关，但与可溶性免疫激活标志物CD14和CD163的浓度无关。
围产期HIV感染后早期有效的联合抗逆转录病毒疗法并长期抑制病毒学，可使青少年外周血前病毒储存库微不足道，并与HIV血清学阴性或不确定状态相关。这些发现突出了早期有效控制HIV复制对围产期感染中HIV持续存在生物标志物的长期影响，以及HIV血清学状态作为小前病毒储存库大小生物标志物的效用，尽管不一定用于治愈。
