HIV-1 潜伏库大小和多样性在短暂治疗中断后保持稳定。
HIV-1 latent reservoir size and diversity are stable following brief treatment interruption.
机构信息
University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Harvard University, Cambridge, Massachusetts, USA.
出版信息
J Clin Invest. 2018 Jul 2;128(7):3102-3115. doi: 10.1172/JCI120194. Epub 2018 Jun 18.
BACKGROUND
The effect of a brief analytical treatment interruption (ATI) on the HIV-1 latent reservoir of individuals who initiate antiretroviral therapy (ART) during chronic infection is unknown.
METHODS
We evaluated the impact of transient viremia on the latent reservoir in participants who underwent an ATI and at least 6 months of subsequent viral suppression in a clinical trial testing the effect of passive infusion of the broadly neutralizing Ab VRC01 during ATI.
RESULTS
Measures of total HIV-1 DNA, cell-associated RNA, and infectious units per million cells (IUPM) (measured by quantitative viral outgrowth assay [QVOA]) were not statistically different before or after ATI. Phylogenetic analyses of HIV-1 env sequences from QVOA and proviral DNA demonstrated little change in the composition of the virus populations comprising the pre- and post-ATI reservoir. Expanded clones were common in both QVOA and proviral DNA sequences. The frequency of clonal populations differed significantly between QVOA viruses, proviral DNA sequences, and the viruses that reactivated in vivo.
CONCLUSIONS
The results indicate that transient viremia from ATI does not substantially alter measures of the latent reservoir, that clonal expansion is prevalent within the latent reservoir, and that characterization of latent viruses that can reactivate in vivo remains challenging.
TRIAL REGISTRATION
ClinicalTrials.gov NCT02463227FUNDING. Funding was provided by the NIH.
背景
在慢性感染期间开始接受抗逆转录病毒治疗（ART）的个体中，短暂分析性治疗中断（ATI）对 HIV-1 潜伏库的影响尚不清楚。
方法
我们评估了在一项临床试验中接受 ATI 且随后至少 6 个月病毒抑制的参与者中转瞬性病毒血症对潜伏库的影响，该试验测试了在 ATI 期间被动输注广泛中和抗体 VRC01 的效果。
结果
在 ATI 前后，HIV-1 DNA 总量、细胞相关 RNA 和每百万个细胞的感染单位（通过定量病毒外生测定法 [QVOA] 测量）（IUPM）的测量值没有统计学差异。来自 QVOA 和前病毒 DNA 的 HIV-1 env 序列的系统发生分析表明，构成 ATI 前后储库的病毒群体组成几乎没有变化。在 QVOA 和前病毒 DNA 序列中均常见扩展克隆。克隆群体的频率在 QVOA 病毒、前病毒 DNA 序列和体内重新激活的病毒之间存在显著差异。
结论
结果表明，ATI 引起的短暂病毒血症不会显著改变潜伏库的测量值，克隆扩增在潜伏库中普遍存在，并且对体内可重新激活的潜伏病毒的特征仍然具有挑战性。
试验注册
ClinicalTrials.gov NCT02463227 资金来源。资金由 NIH 提供。
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