
一旦启动抗逆转录病毒治疗(ART),HIV感染者应坚持终生服药。实际生活中很多情况可能需要暂时中断治疗。在评估某种方案功能性治愈的效果时,需在经过一段时间治疗、血浆HIV降低到一定水平后,停药观察病毒复制情况。若未达到功能性治愈,中断治疗后病毒会反弹。重新启用抗病毒治疗后,病毒能被抑制,但细胞内HIV能否降到停药之前的最低水平,一直被人们所关注。Papasavvas E等分析治疗中断(analytical treatment interruptions,ATI)期间、以及再次启动ART抑制血浆HIV后,细胞内HIV水平的变化。
研究者对23例启动ART达到病毒抑制的慢性HIV感染者在实施ATI的不同时间点【ATI开始前(基线)、ATI期间和重新ART再次抑制HIV后】的周围血单核细胞(PBMC)进行分析。用流式细胞术检测T细胞活化情况,微滴数字聚合酶链反应 (ddPCR)检测细胞HIV DNA和游离的2-长末端重复(2-LTR)环。用逆转录-ddPCR检测细胞HIV多重剪接RNA (tat/rev)、非剪接RNA (gag)和多聚(A)尾(poly(A))。用R软件及JMP Pro进行分析。
结果发现,ATI 期间(中位时间4周),血浆HIV RNA水平显著增加(中位数= 72900拷贝/毫升), CD4+ T细胞计数减少 (中位数= 511.5/μl; P = 0.0001), T细胞活化增加,细胞内HIV DNA和RNA增加。ATI 开始前CD4 HLA-DR T细胞上CD38荧光强度与ATI期间HIV DNA总量水平呈正相关(pol: P = 0.03, Rho = 0.44)。重新开始抗病毒治疗ART后13周血浆HIV 再次被抑制,进而恢复ATI 前的CD4+ T细胞、T细胞活化、细胞内HIV DNA和RNA水平。

图 重新启动ART达到病毒再次抑制后,ATI期间升高的细胞内HIV DNA和RNA水平逐步恢复到治疗中断前水平。
(a) cellular HIV DNA [total HIV DNA ( pol copies) and episomal 2-long terminal repeat (2-LTR) circles] at baseline of ATI while on ART (time point 1), during ATI (time point 2), and following ART-mediated HIV RNA re-suppression (time points 3 and 4). (b) cellular HIV multiply spliced RNA (tat/rev), unspliced (gag), and poly(A) tailed transcripts [poly(A)] at baseline of ATI while on ART (time point 1), during ATI (time point 2), and following ART-mediated HIV RNA re-suppression (time point 3). Data are shown per patient during follow-up with inter-quartile box plots with median and outliers, and significant P values. Different symbols/colors were used per patient as indicated in the side of the figure. Log10 values of each variable were used in the plots to better show the spread of the values (particularly at baseline and post-ATI). ATI, analytical treatment interruption.
文献来源:
Papasavvas E, Lada SM, Joseph J, et al. Analytical antiretroviral therapy interruption does not irreversibly change preinterruption levels of cellular HIV. AIDS. 2018. 32(13): 1763-1772
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