Vela Liliana C, Carrere Leah, Naasz Chloe, Kalavacherla Sruthi, Tan Toong Seng, de Armas Lesley, Gao Ce, Yu Xu G, Pahwa Savita G, Luzuriaga Katherine, Lichterfeld Mathias
Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts, USA.
Infectious Disease Division, Brigham and Women's Hospital, Boston, Massachusetts, USA.
JCI Insight. 2024 Nov 14;10(1):e186550. doi: 10.1172/jci.insight.186550.
HIV-1 reservoir cells persist indefinitely during suppressive antiretroviral therapy (ART) in individuals who acquire infection in adulthood, but little is known about the longitudinal evolution of viral reservoir cells during long-term ART started during early infancy. We studied 2 fraternal twins who acquired HIV-1 perinatally, started ART at week 10 after birth and remained on ART for 28 years. We observed that the frequency of genome-intact proviruses, determined by single-genome near-full-length proviral sequencing, declined by approximately 4,000- to 13,000-fold during this period, indicating enhanced decay rates of intact proviruses even after adjusting for dilution effects from somatic growth. Despite analyzing more than one billion PBMC after 28 years of ART in each participant, no intact proviruses were detected in 1 participant, and 1 intact provirus was isolated in the other. The longitudinal decline of defective proviruses in the 2 participants was more similar to proviral decay kinetics reported in individuals who started ART during adulthood; moreover, clonal sequence clusters were readily detectable for defective proviruses but not for intact proviruses after 28 years of ART in the 2 twins. Together, these data suggest decreased long-term stability and increased immunological vulnerability of intact proviruses during long-term ART started in early infancy.
在成年期感染HIV-1的个体接受抑制性抗逆转录病毒疗法（ART）期间，HIV-1储存库细胞会无限期持续存在，但对于婴儿早期开始长期ART治疗期间病毒储存库细胞的纵向演变知之甚少。我们研究了2对同卵双胞胎，他们在围产期感染了HIV-1，出生后第10周开始接受ART治疗，并持续接受ART治疗28年。我们观察到，通过单基因组近全长前病毒测序确定的基因组完整前病毒的频率在此期间下降了约4000至13000倍，这表明即使在调整了体细胞生长的稀释效应后，完整前病毒的衰减率仍有所提高。尽管在每位参与者接受28年ART治疗后分析了超过10亿个外周血单核细胞（PBMC），但在1名参与者中未检测到完整前病毒，在另一名参与者中分离出1个完整前病毒。这2名参与者中缺陷前病毒的纵向下降与成年期开始接受ART治疗的个体中报道的前病毒衰减动力学更为相似；此外，在这2对双胞胎接受28年ART治疗后，缺陷前病毒的克隆序列簇很容易检测到，而完整前病毒则不然。这些数据共同表明，在婴儿早期开始长期ART治疗期间，完整前病毒的长期稳定性降低，免疫脆弱性增加。
