De Rossi A, Masiero S, Giaquinto C, Ruga E, Comar M, Giacca M, Chieco-Bianchi L
Institute of Oncology, InterUniversity Center for Cancer Research, AIDS Reference Center, University of Padova, Italy.
J Clin Invest. 1996 Jan 15;97(2):323-30. doi: 10.1172/JCI118419.
About one-third of vertically HIV-1 infected infants develop AIDS within the first months of life; the remainder show slower disease progression. We investigated the relationship between the pattern of HIV-1 replication early in life and disease outcome in eleven infected infants sequentially studied from birth. Viral load in cells and plasma was measured by highly sensitive competitive PCR-based methods. Although all infants showed an increase in the indices of viral replication within their first weeks of life, three distinct patterns emerged: (a) a rapid increase in plasma viral RNA and cell-associated proviral DNA during the first 4-6 wk, reaching high steady state levels (> 1,000 HIV-1 copies/10(5) PBMC and > 1,000,000 RNA copies/ml plasma) within 2-3 mo of age; (b) a similar initial rapid increase in viral load, followed by a 2.5-50-fold decline in viral levels; (c) a significantly lower (> 10-fold) viral increase during the first 4-6 wk of age. All infants displaying the first pattern developed early AIDS, while infants with slower clinical progression exhibited the second or third pattern. These findings demonstrate that the pattern of viral replication and clearance in the first 2-3 mo of life is strictly correlated with, and predictive of disease evolution in vertically infected infants.
约三分之一垂直感染HIV-1的婴儿在出生后的头几个月内发展为艾滋病;其余婴儿的疾病进展则较为缓慢。我们对11名从出生起就接受连续研究的感染婴儿进行了调查,以研究生命早期HIV-1复制模式与疾病转归之间的关系。通过基于高灵敏度竞争性PCR的方法测量细胞和血浆中的病毒载量。尽管所有婴儿在出生后的头几周内病毒复制指标均有所增加,但出现了三种不同的模式:(a) 在出生后的前4 - 6周内,血浆病毒RNA和细胞相关前病毒DNA迅速增加,在2 - 3月龄时达到高稳态水平(>1000个HIV-1拷贝/10⁵外周血单核细胞且>1000000个RNA拷贝/毫升血浆);(b) 病毒载量最初有类似的快速增加,随后病毒水平下降2.5 - 50倍;(c) 在出生后的前4 - 6周内病毒增加明显较低(>10倍)。所有表现出第一种模式的婴儿都早早患上了艾滋病,而临床进展较慢的婴儿则表现出第二种或第三种模式。这些发现表明,出生后2 - 3个月内的病毒复制和清除模式与垂直感染婴儿的疾病演变密切相关,并可预测疾病演变。