Ruiz L, Martinez-Picado J, Romeu J, Paredes R, Zayat M K, Marfil S, Negredo E, Sirera G, Tural C, Clotet B
Retrovirology Laboratory irsiCaixa Foundation, University Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain.
AIDS. 2000 Mar 10;14(4):397-403. doi: 10.1097/00002030-200003100-00013.
To investigate the virological and immunological impact of a structured treatment interruption (STI) in a cohort of HIV-1 chronically infected patients with a further long-lasting effective virus suppression.
Twelve HIV-1 chronically infected adults who had maintained viral suppression (< 20 copies/ml) for more than 2 years, as well as a CD4:CD8 ratio > 1 for a median time of 22 months, were included in the study. Participants interrupted their antiretroviral treatment during a maximum period of 30 days or until a viral load rebound > 3000 copies/ml was detected. The same prior antiretroviral regimen was resumed after STI. Kinetics of plasma viral rebound was evaluated every 2 days during the treatment interruption period. Flow cytometry and cell proliferation assays were performed before and after STI. Genotypic resistance was assessed at the time of treatment resumption.
No adverse events occurred during the interruption period. In two patients no viral rebound was detected after 30 days of treatment interruption. In the remaining 10 patients, viral load became detectable (> 20 copies/ml) at a median time of 14 days after treatment interruption. Afterwards, viral load increased exponentially with a mean t1/2 of 1.6 days. Treatment was successfully resumed in all patients. No resistance-conferring mutations associated with the pre-interruption antiretroviral regimen were detected. The percentage of CD4 and CD8 lymphocytes did not vary during the STI period; however, the level of expression of T-cell activation antigen CD38 on CD8 T cells increased significantly in response to viral rebound. Four patients gained T-helper cell responses to recall antigens (tuberculin and tetanus toxoid), two of who developed an HIV-specific response to p24.
STI in chronically HIV-1-infected patients is not associated with reductions in CD4 T lymphocytes or to clinical complications in this group of patients after 2 years of effective plasma viral suppression. Viral load rebounds in most but not all patients, without evidence of selection of resistance-conferring mutations. Thereafter, viraemia can be effectively controlled by antiretroviral agent reintroduction. HIV-specific T-helper cell responses may be achieved after one cycle of treatment interruption suggesting some degree of immune-stimulation. These data do not discard consecutive cycles of STI as a therapeutic strategy to boost HIV-specific immunity in order to maintain viral replication under effective control.
在一组长期有效抑制病毒的HIV-1慢性感染患者中，研究结构化治疗中断（STI）对病毒学和免疫学的影响。
12名HIV-1慢性感染的成年人被纳入研究，他们已维持病毒抑制状态（<20拷贝/毫升）超过2年，且CD4:CD8比值>1的中位时间为22个月。参与者在最长30天的时间内中断抗逆转录病毒治疗，或直至检测到病毒载量反弹>3000拷贝/毫升。STI后恢复使用相同的先前抗逆转录病毒方案。在治疗中断期间，每2天评估血浆病毒反弹的动力学。在STI前后进行流式细胞术和细胞增殖测定。在恢复治疗时评估基因型耐药性。
中断期间未发生不良事件。2名患者在治疗中断30天后未检测到病毒反弹。在其余10名患者中，治疗中断后中位14天病毒载量变得可检测（>20拷贝/毫升）。此后，病毒载量呈指数增长，平均半衰期为1.6天。所有患者均成功恢复治疗。未检测到与中断前抗逆转录病毒方案相关的耐药性突变。在STI期间，CD4和CD8淋巴细胞的百分比没有变化；然而，随着病毒反弹，CD8 T细胞上T细胞活化抗原CD38的表达水平显著增加。4名患者对回忆抗原（结核菌素和破伤风类毒素）产生了T辅助细胞反应，其中2名患者对p24产生了HIV特异性反应。
在HIV-1慢性感染患者中，经过2年有效的血浆病毒抑制后，STI与CD4 T淋巴细胞减少或该组患者的临床并发症无关。大多数但并非所有患者的病毒载量都会反弹，且没有选择耐药性突变的证据。此后，通过重新引入抗逆转录病毒药物可以有效控制病毒血症。在一个治疗中断周期后可能会实现HIV特异性T辅助细胞反应，这表明有一定程度的免疫刺激。这些数据并不排除将连续的STI周期作为一种治疗策略来增强HIV特异性免疫力，以便在有效控制下维持病毒复制。
