Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Howard Hughes Medical Institute, Baltimore, Maryland, USA.
J Clin Invest. 2020 Nov 2;130(11):5665-5667. doi: 10.1172/JCI141497.
Antiretroviral therapy (ART) generally reduces plasma HIV to undetectable levels, although virus persists in latently infected CD4+ T cells. In some individuals, viremia remains detectable despite adherence to ART and the absence of drug resistance mutations. In this issue of the JCI, Halvas et al. describe HIV RNA sequences from plasma of 8 donors with persistent viremia. Residual viremia was dominated by identical HIV-1 RNA sequences that remained relatively constant over 4 years. Plasma virus matched replication-competent virus cultured from CD4+ T cells. Integration site analysis confirmed the presence of large clones of infected cells. These results indicate that nonsuppressible viremia can be due to expanded clones of infected CD4+ T cells carrying replication-competent virus. The individuals described here represent extreme examples of a phenomenon that is seen in all infected individuals and that is a major barrier to curing HIV infection, the in vivo proliferation of latently infected cells.
抗逆转录病毒疗法（ART）通常可将血浆 HIV 降低至检测不到的水平，尽管病毒仍存在于潜伏感染的 CD4+T 细胞中。在某些个体中，尽管依从性好且不存在耐药性突变，但病毒血症仍可检测到。在本期 JCI 中，Halvas 等人描述了来自 8 名持续性病毒血症供者的血浆中的 HIV RNA 序列。残留的病毒血症主要由相同的 HIV-1 RNA 序列主导，这些序列在 4 年内相对稳定。来自 CD4+T 细胞的培养物与血浆病毒相匹配，具有复制能力的病毒。整合位点分析证实了感染细胞的大克隆的存在。这些结果表明，无法抑制的病毒血症可能是由于携带具有复制能力的病毒的感染 CD4+T 细胞的扩增克隆所致。这里描述的个体代表了所有感染个体中均可见的现象的极端例子，这是治愈 HIV 感染的主要障碍，即潜伏感染细胞的体内增殖。
