Department of Chemical Engineering, Indian Institute of Science, Bangalore, Karnataka, 560012, India.
Division of Infectious Diseases, St. John's Research Institute, St. John's National Academy of Health Sciences, Bangalore, India.
Sci Rep. 2021 Feb 4;11(1):2990. doi: 10.1038/s41598-021-82293-2.
As the immune system develops with age, children combat infections better. HIV-1, however, targets an activated immune system, potentially rendering children increasingly permissive to HIV-1 infection as they grow. How HIV-1 fitness changes with age in children is unknown. Here, we estimated the within-host basic reproductive ratio, R, a marker of viral fitness, in HIV-1 subtype C-infected children in India, aged between 84 days and 17 years. We measured serial viral load and CD4 T cell counts in 171 children who initiated first-line ART. For 25 children, regular and frequent measurements provided adequate data points for analysis using a mathematical model of viral dynamics to estimate R. For the rest, we used CD4 counts for approximate estimation of R. The viral load decline during therapy was biphasic. The mean lifespans of productively and long-lived infected cells were 1.4 and 27.8 days, respectively. The mean R was 1.5 in children aged < 5 years, increased with age, and approached 6.0 at 18 years, close to 5.8 estimated previously for adults. The tolerogenic immune environment thus compromises HIV-1 fitness in young children. Early treatment initiation, when the R is small, will likely improve viral control, in addition to suppressing the latent reservoir.
随着免疫系统随年龄的增长而发育，儿童抗感染的能力会增强。然而，HIV-1 靶向的是激活的免疫系统，这可能使儿童随着年龄的增长对 HIV-1 感染变得越来越易感。HIV-1 在儿童中的适应度如何随年龄变化尚不清楚。在这里，我们估计了在印度感染 HIV-1 亚型 C 的儿童的宿主内基本繁殖数 R，R 是病毒适应度的一个标志，这些儿童的年龄在 84 天至 17 岁之间。我们测量了 171 名首次接受一线抗逆转录病毒治疗的儿童的连续病毒载量和 CD4 T 细胞计数。对于 25 名儿童，定期和频繁的测量提供了足够的数据点，我们使用病毒动力学的数学模型来分析这些数据，以估计 R。对于其余儿童，我们使用 CD4 计数进行 R 的近似估计。治疗期间病毒载量的下降呈双相性。有活力和长期存活的感染细胞的平均寿命分别为 1.4 天和 27.8 天。<5 岁儿童的平均 R 值为 1.5，随着年龄的增长而增加，并在 18 岁时接近 6.0，接近之前对成年人估计的 5.8。因此，耐受的免疫环境会损害幼儿的 HIV-1 适应度。早期治疗开始时，R 值较小，除了抑制潜伏库外，还可能改善病毒控制。
