Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts Division of Infectious Diseases, Weill Cornell Medicine, New York, New York Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health Department of Microbiology, Boston University School of Medicine, Boston, Massachusetts Department of Infectious Diseases and Microbiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, Pennsylvania Social & Scientific Systems, Inc., Silver Spring, Maryland Department of Medicine, University of North Carolina, Chapel Hill, North Carolina Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
AIDS. 2020 Jan 1;34(1):15-24. doi: 10.1097/QAD.0000000000002406.
We evaluated frequencies of T cells with high PD-1 expression (PD-1) before and after long-term effective antiretroviral therapy (ART), and determined if frequencies on-ART correlated positively with measures of HIV persistence and negatively with HIV-specific responses.
We enrolled individuals who started ART during chronic infection and had durable suppression of viremia for at least 4 years (N = 99). We assessed PD-1 T-cell frequencies at timepoints pre-ART and on-ART using flow cytometry, and evaluated how frequencies on-ART are associated with measures of HIV persistence, HIV-specific immune responses, and immune activation levels.
Pre-ART, PD-1 CD4 T cells correlated positively with viremia and negatively with CD4 T-cell count. At year 1 on-ART, %PD-1 CD4 T cells decreased but then remained stable at 4 and 6-15 years on-ART, whereas %PD-1 CD8 T cells on-ART remained similar to pre-ART. PD-1 CD4 T cells correlated positively with HIV DNA pre-ART and on-ART, and with CD4 T-cell activation on-ART. PD-1 CD4 T cells negatively correlated with HIV Gag-specific and Env-specific T-cell responses but not with CMV-specific or EBV-specific responses. PD-1 CD8 T cells trended towards a negative correlation with responses to Gag and Env, but not to CMV and EBV.
PD-1 T cells persist in blood despite prolonged suppression on ART, correlate with HIV DNA levels, and are associated with lower HIV-specific T-cell responses but not CMV-specific or EBV-specific responses, suggesting that these cells are HIV-specific. The findings support evaluating PD-1 blockade strategies for their effect on HIV persistence and HIV-specific immunity.
我们评估了长期有效抗逆转录病毒治疗（ART）前后高 PD-1 表达（PD-1）T 细胞的频率，并确定了 ART 时的频率是否与 HIV 持续存在呈正相关，与 HIV 特异性反应呈负相关。
我们招募了在慢性感染期间开始 ART 并至少 4 年维持病毒血症抑制的个体（N=99）。我们使用流式细胞术在 ART 前和 ART 时评估 PD-1 T 细胞频率，并评估 ART 时的频率与 HIV 持续存在、HIV 特异性免疫反应和免疫激活水平的相关性。
ART 前，PD-1 CD4 T 细胞与病毒血症呈正相关，与 CD4 T 细胞计数呈负相关。在 ART 第 1 年，%PD-1 CD4 T 细胞减少，但随后在 ART 第 4 年和第 6-15 年保持稳定，而 ART 时的%PD-1 CD8 T 细胞仍与 ART 前相似。PD-1 CD4 T 细胞与 HIV DNA 呈正相关ART 前和 ART，以及 ART 时 CD4 T 细胞激活。PD-1 CD4 T 细胞与 HIV Gag 特异性和 Env 特异性 T 细胞反应呈负相关，但与 CMV 特异性或 EBV 特异性反应无关。PD-1 CD8 T 细胞与 Gag 和 Env 的反应呈负相关趋势，但与 CMV 和 EBV 无关。
尽管在 ART 上长期抑制，PD-1 T 细胞仍在血液中持续存在，与 HIV DNA 水平相关，与 HIV 特异性 T 细胞反应较低有关，但与 CMV 特异性或 EBV 特异性反应无关，提示这些细胞为 HIV 特异性。这些发现支持评估 PD-1 阻断策略对 HIV 持续存在和 HIV 特异性免疫的影响。
