Human immunodeficiency virus (HIV)-induced changes in immune cells during the acute phase of infection can cause irreversible immunological damage and predict the rate of disease progression. Antiretroviral therapy (ART) remains the most effective strategy for successful immune restoration in immunocompromised people living with HIV and the earlier ART is initiated after infection, the better the long-term clinical outcomes. Here we explored the effect of ART on peripheral antigen presenting cell (APC) phenotype and function in women with HIV-1 subtype C infection who initiated ART in the hyperacute phase (before peak viremia) or during chronic infection. Peripheral blood mononuclear cells obtained longitudinally from study participants were used for immunophenotyping and functional analysis of monocytes and dendritic cells (DCs) using multiparametric flow cytometry and matched plasma was used for measurement of inflammatory markers IL-6 and soluble CD14 (sCD14) by enzyme-linked immunosorbent assay. HIV infection was associated with expansion of monocyte and plasmacytoid DC (pDC) frequencies and perturbation of monocyte subsets compared to uninfected persons despite antiretroviral treatment during hyperacute infection. Expression of activation marker CD69 on monocytes and pDCs in early treated HIV was similar to uninfected individuals. However, despite early ART, HIV infection was associated with elevation of plasma IL-6 and sCD14 levels which correlated with monocyte activation. Furthermore, HIV infection with or without early ART was associated with downmodulation of the co-stimulatory molecule CD86. Notably, early ART was associated with preserved toll-like receptor (TLR)-induced IFN-α responses of pDCs. Overall, this data provides evidence of the beneficial impact of ART initiated in hyperacute infection in preservation of APC functional cytokine production activity; but also highlights persistent inflammation facilitated by monocyte activation even after prolonged viral suppression and suggests the need for therapeutic interventions that target residual immune activation.

在感染的急性期，人类免疫缺陷病毒 (HIV) 诱导的免疫细胞变化可导致不可逆的免疫损伤并预测疾病进展的速度。抗逆转录病毒疗法 (ART) 仍然是免疫功能低下的 HIV 感染者成功恢复免疫的最有效策略，感染后越早开始 ART，长期临床结果越好。在这里，我们探讨了 ART 对 HIV-1 C 亚型感染女性的外周抗原呈递细胞 (APC) 表型和功能的影响，这些女性在超急性期（病毒血症高峰之前）或慢性感染期间开始 ART。从研究参与者纵向获得的外周血单个核细胞用于使用多参数流式细胞术对单核细胞和树突细胞 (DC) 进行免疫表型和功能分析，并使用匹配的血浆通过酶测量炎症标志物 IL-6 和可溶性 CD14 (sCD14)。联免疫吸附试验。尽管在超急性感染期间接受了抗逆转录病毒治疗，但与未感染者相比，HIV 感染与单核细胞和浆细胞样 DC (pDC) 频率的扩张和单核细胞亚群的扰动有关。在早期治疗的 HIV 中，单核细胞和 pDC 上活化标记 CD69 的表达与未感染的个体相似。然而，尽管早期 ART，HIV 感染与血浆 IL-6 和 sCD14 水平升高有关，这与单核细胞活化相关。此外，有或没有早期 ART 的 HIV 感染与共刺激分子 CD86 的下调有关。值得注意的是，早期 ART 与保留的 Toll 样受体 (TLR) 诱导的 pDC 的 IFN-α 反应有关。总体而言，该数据提供了在超急性感染中启动 ART 对保持 APC 功能性细胞因子产生活性的有益影响的证据；但也强调了即使在长时间的病毒抑制后，单核细胞激活也会促进持续炎症，并表明需要针对残留免疫激活进行治疗干预。该数据提供了在超急性感染中启动 ART 对保持 APC 功能性细胞因子产生活性的有益影响的证据；但也强调了即使在长时间的病毒抑制后，单核细胞激活也会促进持续炎症，并表明需要针对残留免疫激活进行治疗干预。该数据提供了在超急性感染中启动 ART 对保持 APC 功能性细胞因子产生活性的有益影响的证据；但也强调了即使在长时间的病毒抑制后，单核细胞激活也会促进持续炎症，并表明需要针对残留免疫激活进行治疗干预。