Department of Infectious Diseases, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.
Department of Infectious Diseases, Aarhus University Hospital, AarhusDenmark.
Clin Infect Dis. 2022 Nov 14;75(10):1781-1791. doi: 10.1093/cid/ciac249.
Identifying factors that determine the frequency of latently infected CD4+ T cells on antiretroviral therapy (ART) may inform strategies for human immunodeficiency virus (HIV) cure. We investigated the role of CD4+ count at ART initiation for HIV persistence on ART.
Among participants of the Strategic Timing of Antiretroviral Treatment Study, we enrolled people with HIV (PWH) who initiated ART with CD4+ T-cell counts of 500-599, 600-799, or ≥ 800 cells/mm3. After 36-44 months on ART, the levels of total HIV-DNA, cell-associated unspliced HIV-RNA (CA-US HIV-RNA), and two-long terminal repeat HIV-DNA in CD4+ T cells were quantified and plasma HIV-RNA was measured by single-copy assay. We measured T-cell expression of Human Leucocyte Antigen-DR Isotype (HLA-DR), programmed death-1, and phosphorylated signal transducer and activator of transcription-5 (pSTAT5). Virological and immunological measures were compared across CD4+ strata.
We enrolled 146 PWH, 36 in the 500-599, 60 in the 600-799, and 50 in the ≥ 800 CD4 strata. After 36-44 months of ART, total HIV-DNA, plasma HIV-RNA, and HLA-DR expression were significantly lower in PWH with CD4+ T-cell count ≥ 800 cells/mm3 at ART initiation compared with 600-799 or 500-599 cells/mm3. The median level of HIV-DNA after 36-44 months of ART was lower by 75% in participants initiating ART with ≥ 800 vs 500-599 cells/mm3 (median [interquartile range]: 16.3 [7.0-117.6] vs 68.4 [13.7-213.1] copies/million cells, respectively). Higher pSTAT5 expression significantly correlated with lower levels of HIV-DNA and CA-US HIV-RNA. Virological measures were significantly lower in females.
Initiating ART with a CD4+ count ≥ 800 cells/mm3 compared with 600-799 or 500-599 cells/mm3 was associated with achieving a substantially smaller HIV reservoir on ART.
确定抗逆转录病毒治疗（ART）期间潜伏感染的 CD4+T 细胞频率的决定因素，可能为人类免疫缺陷病毒（HIV）的治愈策略提供信息。我们研究了在 ART 期间，CD4+计数在 HIV 持续存在中的作用。
在战略时机抗逆转录病毒治疗研究中，我们招募了 CD4+T 细胞计数为 500-599、600-799 或≥800 个/立方毫米的开始 ART 的 HIV 感染者（PWH）。在接受 ART 36-44 个月后，定量检测 CD4+T 细胞中总 HIV-DNA、细胞相关未剪接 HIV-RNA（CA-US HIV-RNA）和两个长末端重复 HIV-DNA 的水平，并通过单拷贝检测测量血浆 HIV-RNA。我们测量了 T 细胞表达人类白细胞抗原-DR 同种型（HLA-DR）、程序性死亡-1 和磷酸化信号转导和转录激活因子 5（pSTAT5）。在 CD4 层之间比较病毒学和免疫学指标。
我们招募了 146 名 PWH，其中 36 名在 500-599 个/立方毫米，60 名在 600-799 个/立方毫米，50 名在≥800 个/立方毫米。在接受 ART 36-44 个月后，与 600-799 或 500-599 个/立方毫米相比，开始 ART 时 CD4+T 细胞计数≥800 个/立方毫米的 PWH 中，总 HIV-DNA、血浆 HIV-RNA 和 HLA-DR 表达明显更低。在接受 ART 36-44 个月后，与开始 ART 时 CD4+计数为 500-599 个/立方毫米的患者相比，开始 ART 时 CD4+计数为≥800 个/立方毫米的患者的 HIV-DNA 中位数水平降低了 75%（中位数[四分位距]：16.3[7.0-117.6]对 68.4[13.7-213.1]拷贝/百万细胞，分别）。更高的 pSTAT5 表达与更低的 HIV-DNA 和 CA-US HIV-RNA 水平显著相关。女性的病毒学指标明显较低。
与 600-799 或 500-599 个/立方毫米相比，开始 ART 时 CD4+计数≥800 个/立方毫米与 ART 期间实现更小的 HIV 储存库相关。
