Papasavvas Emmanouil, Kostman Jay R, Thiel Brian, Pistilli Maxwell, Mackiewicz Agnieszka, Foulkes Andrea, Gross Robert, Jordan Kimberly A, Nixon Douglas F, Grant Robert, Poulin Jean-Francois, McCune Joseph M, Mounzer Karam, Montaner Luis J
The Wistar Institute, Philadelphia, Pennsylvania 19104, USA.
J Clin Immunol. 2006 Jan;26(1):40-54. doi: 10.1007/s10875-006-7518-8.
The impact of transient viral load blips on anti-HIV-1 immune responses and on HIV-1 rebound following treatment interruption (TI) is not known. Clinical and immunological parameters were measured during 40 weeks of antiretroviral therapy (ART) and following TI in an observational cohort of 16 chronically HIV-1-infected subjects with or without observed viral load blips during ART. During therapy, blips in seven subjects were associated with higher anti-HIV-1 (p24) CD4+ T cell lymphoproliferative responses (p = 0.04), without a significant difference in T cell activation or total anti-HIV-1 CD8+ T cell interferon-gamma (IFN-gamma) responses when compared to nine matched non-blippers. Therapy interruption resulted in a significantly higher viral rebound in blippers by 8 week despite retention of higher lymphoproliferative p24 responses (p = 0.01) and a rise in CD3+ T cell activation (p = 0.04) and anti-HIV-1 CD8+ T cell responses in blippers by week 4 when compared to non-blippers. Past week 4 of interruption, therapy re-initiation criteria were also met by a higher frequency in blippers by week 14 (p < 0.04) with no difference between groups by week 24. These data support that blippers have higher anti-HIV lymphoproliferative responses while on ART but experience equal to higher viral rebound as compared to matched non-blippers upon TI.
短暂性病毒载量波动对抗HIV-1免疫反应以及治疗中断(TI)后HIV-1反弹的影响尚不清楚。在一项观察性队列研究中,对16名慢性HIV-1感染受试者在40周抗逆转录病毒治疗(ART)期间及治疗中断后进行了临床和免疫学参数测量,这些受试者在ART期间有或没有观察到病毒载量波动。在治疗期间,7名出现波动的受试者的抗HIV-1(p24)CD4+T细胞淋巴细胞增殖反应较高(p = 0.04),与9名匹配的未出现波动者相比,T细胞活化或总抗HIV-1 CD8+T细胞干扰素-γ(IFN-γ)反应无显著差异。尽管出现波动者在第4周时保留了较高的淋巴细胞增殖性p24反应(p = 0.01),且CD3+T细胞活化增加(p = 0.04)以及抗HIV-1 CD8+T细胞反应增加,但治疗中断导致出现波动者在第8周时病毒反弹明显更高。与未出现波动者相比,在中断治疗4周后,出现波动者在第14周时达到治疗重新启动标准的频率也更高(p < 0.04),到第24周时两组之间无差异。这些数据支持,出现波动者在接受ART治疗时具有较高的抗HIV淋巴细胞增殖反应,但与匹配的未出现波动者相比,在治疗中断时经历了同等程度或更高的病毒反弹。