Deeks Steven G, Martin Jeffrey N, Sinclair Elizabeth, Harris Jeff, Neilands Torsten B, Maecker Holden T, Hagos Elilta, Wrin Terri, Petropoulos Christos J, Bredt Barry, McCune Joseph M
Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
J Infect Dis. 2004 Jan 15;189(2):312-21. doi: 10.1086/380098. Epub 2004 Jan 7.
Antiretroviral (ARV)-treated patients often maintain low to moderate levels of viremia, despite the emergence of drug-resistant human immunodeficiency virus (HIV). We studied host and viral factors that may contribute to the control of viral replication in a cohort of 189 adults. Among ARV-treated patients with detectable viremia, there was a bell-shaped relationship between Gag-specific CD4+ T cell responses and viremia, with the highest cellular immune responses observed in patients with plasma HIV RNA levels of 1000-10,000 copies/mL. In contrast, there was a negative association between Gag-specific CD4+ T cell responses and viremia among ARV-untreated individuals with wild-type HIV. Strong cellular immune responses among individuals with drug-resistant HIV predicted subsequent lack of virological progression. Finally, there was a positive correlation between replicative capacity and viremia. Collectively, these data suggest that the selection of drug-resistance mutations may reduce the pathogenic potential of HIV, which leads to a balanced state of enhanced cellular immunity and low-level viremia.
尽管出现了耐药性人类免疫缺陷病毒（HIV），接受抗逆转录病毒（ARV）治疗的患者通常仍维持低至中度的病毒血症水平。我们在189名成年人队列中研究了可能有助于控制病毒复制的宿主和病毒因素。在可检测到病毒血症的接受ARV治疗的患者中，Gag特异性CD4+ T细胞反应与病毒血症之间呈钟形关系，在血浆HIV RNA水平为1000 - 10000拷贝/毫升的患者中观察到最高的细胞免疫反应。相比之下，在感染野生型HIV且未接受ARV治疗的个体中，Gag特异性CD4+ T细胞反应与病毒血症之间呈负相关。耐药HIV个体中的强烈细胞免疫反应预示着随后缺乏病毒学进展。最后，复制能力与病毒血症之间呈正相关。总体而言，这些数据表明耐药性突变的选择可能会降低HIV的致病潜力，从而导致细胞免疫增强和低水平病毒血症的平衡状态。
