Uprety Priyanka, Patel Kunjal, Karalius Brad, Ziemniak Carrie, Chen Ya Hui, Brummel Sean S, Siminski Suzanne, Van Dyke Russell B, Seage George R, Persaud Deborah
W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
Department of Epidemiology/Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
Clin Infect Dis. 2017 Jun 1;64(11):1471-1478. doi: 10.1093/cid/cix192.
BACKGROUND.: Early antiretroviral therapy (ART) limits proviral reservoirs, a goal for human immunodeficiency virus type 1 (HIV-1) remission strategies. Whether this is an immediate or long-term effect of virologic suppression (VS) in perinatal infection is unknown.
METHODS.: We quantified HIV-1 DNA longitudinally for up to 14 years in peripheral blood mononuclear cells (PBMCs) among 61 perinatally HIV-1-infected youths in the Pediatric HIV/AIDS Cohort Study who achieved VS at different ages. Participants in group 1 (n = 13) were <1 year of age and in group 2 (n = 48) from 1 through 5 years of age at VS. Piecewise linear mixed-effects regression models assessed the effect of age at VS on HIV-1 DNA trajectories during VS.
RESULTS.: In the first 2 years following VS, HIV-1 DNA levels decreased by -0.25 (95% confidence interval [CI], -.36 to -.13) log10 copies/million PBMCs per year and was faster with early VS by age 1 year compared with after age 1 (-0.50 and -0.15 log10 copies/million PBMCs per year, respectively). Between years 2 and 14 from VS, HIV-1 DNA decayed by -0.05 (95% CI, -.06 to -.03) log10 copies/million PBMCs per year and was no longer significantly different between groups. The estimated mean half-life of HIV-1 DNA from VS was 15.9 years and was shorter for group 1 compared to group 2 at 5.9 years and 18.8 years, respectively (P = .09). Adjusting for CD4 cell counts had no effect on decay estimates.
CONCLUSIONS.: Early effective, long-term ART initiated from infancy leads to decay of HIV-1-infected cells to exceedingly low concentrations desired for HIV-1 remission strategies.
早期抗逆转录病毒疗法（ART）可限制前病毒储存库，这是1型人类免疫缺陷病毒（HIV-1）缓解策略的一个目标。在围产期感染中，这是病毒学抑制（VS）的即时效应还是长期效应尚不清楚。
在儿科HIV/艾滋病队列研究中，我们对61名围产期感染HIV-1且在不同年龄实现病毒学抑制的青少年的外周血单核细胞（PBMC）中的HIV-1 DNA进行了长达14年的纵向定量分析。第1组（n = 13）在病毒学抑制时年龄小于1岁，第2组（n = 48）在病毒学抑制时年龄为1至5岁。分段线性混合效应回归模型评估了病毒学抑制时的年龄对病毒学抑制期间HIV-1 DNA轨迹的影响。
在病毒学抑制后的前2年，HIV-1 DNA水平每年下降-0.25（95%置信区间[CI]，-0.36至-0.13）log10拷贝/百万PBMC，1岁时早期病毒学抑制比1岁以后下降更快（分别为每年-0.50和-0.15 log10拷贝/百万PBMC）。从病毒学抑制后第2年到第14年，HIV-1 DNA每年衰减-0.05（95%CI，-0.06至-0.03）log10拷贝/百万PBMC，两组之间不再有显著差异。病毒学抑制后HIV-1 DNA的估计平均半衰期为15.9年，第1组比第2组短，分别为5.9年和18.8年（P = 0.09）。校正CD4细胞计数对衰减估计无影响。
从婴儿期开始的早期有效、长期抗逆转录病毒疗法可使HIV-1感染细胞衰减至极低浓度，这是HIV-1缓解策略所期望的。
