Salpini Romina, D'Anna Stefano, Alkhatib Mohammad, Piermatteo Lorenzo, Tavelli Alessandro, Benedetti Livia, Quiros Roldan Eugenia, Cingolani Antonella, Papalini Chiara, Carrara Stefania, Malagnino Vincenzo, Puoti Massimo, Sarmati Loredana, Ceccherini-Silberstein Francesca, Perno Carlo Federico, Monforte Antonella d'Arminio, Svicher Valentina
Department of Biology, University of Rome Tor Vergata, Rome, Italy.
Department of Experimental Medicine, University of Rome Tor Vergata, Rome, Italy.
Int J Infect Dis. 2025 Jan;150:107294. doi: 10.1016/j.ijid.2024.107294. Epub 2024 Nov 5.
To unravel the still unexplored HBV-replicative kinetics in anti-HBc-positive/HBsAg-negative people-with-HIV (PWH) suspending tenofovir disoproxil-fumarate/tenofovir-alafenamide (TDF/TAF).
A total of 101 anti-HBc-positive/HBsAg-negative PWH switching to TDF/TAF-sparing therapy were included. Serum HBV-DNA and HBV-RNA were quantified by droplet-digital-PCR at switching (T0), within 12 months (T1) and 12-24 months postswitch (T2).
At T0, 33.7% had cryptic HBV-DNA (undetected by commercial assays, median [interquartile range (IQR)]: 2 [1-5] IU/mL) and 22% were positive to HBV-RNA alone (median [IQR]: 4 [3-4] IU/mL), indicating an active HBV-reservoir despite HBsAg-negativity and TDF/TAF-pressure. Notably, anti-HBs-titer <100 mIU/mL independently correlated with cryptic HBV-DNA at T0 (OR [95% CI]: 2.6 [1.02-6.5], P = 0.04). After TDF/TAF-withdrawal, the rate of PWH achieving HBV-DNA >10 IU/mL increased from 12.9% at T1 to 42.6% at T2 (P < 0.0001). Likewise, a rise from 2 to 11% was observed for HBV-DNA >100 IU/mL (P = 0.02); median (IQR) HBV-DNA: 579 (425-770) IU/mL. Notably, HBV-DNA >10 IU/mL at T2 occurred in 70% of PWH with cryptic HBV-DNA, in 38.5% with HBV-RNA alone and in 25% negative to both HBV-markers at T0 (P = 0.01). Cryptic HBV-DNA at T0 and lower nadir CD4+ T-cell-count independently predicted HBV-DNA >10 IU/mL at T2 (OR [95% CI]: 8.2 [1.7-40.6], P = 0.01; OR [95% CI]: 8.1 [1.3-52.1], P = 0.03). Lastly, persistent HBV-DNA positivity was independently associated with a reduced CD4+ T-cell recovery at T2 (OR [95% CI]: 0.07 [0.01-0.77], P = 0.03).
This study underlines the importance to regularly monitor anti-HBc-positive/HBsAg-negative PWH undergoing TDF/TAF-sparing regimen and the role of highly-sensitive HBV markers in optimizing their management.
在停用替诺福韦酯/替诺福韦艾拉酚胺（TDF/TAF）的抗-HBc阳性/HBsAg阴性HIV感染者（PWH）中，揭示尚未探索的HBV复制动力学。
共纳入101例转换为停用TDF/TAF治疗方案的抗-HBc阳性/HBsAg阴性PWH。在转换时（T0）、12个月内（T1）和转换后12 - 24个月（T2），通过液滴数字PCR对血清HBV-DNA和HBV-RNA进行定量。
在T0时，33.7%的患者存在隐匿性HBV-DNA（商业检测未检测到，中位数[四分位间距（IQR）]：2[1 - 5]IU/mL），22%仅HBV-RNA呈阳性（中位数[IQR]：4[3 - 4]IU/mL），这表明尽管HBsAg阴性且有TDF/TAF压力，但仍存在活跃的HBV储存库。值得注意的是，抗-HBs滴度<100 mIU/mL与T0时的隐匿性HBV-DNA独立相关（OR[95%CI]：2.6[1.02 - 6.5]，P = 0.04）。停用TDF/TAF后，HBV-DNA>10 IU/mL的PWH比例从T1时的12.9%增加到T2时的42.6%（P < 0.0001）。同样，HBV-DNA>100 IU/mL的比例从2%上升到11%（P = 0.02）；中位数（IQR）HBV-DNA：579（425 - 770）IU/mL。值得注意的是，T2时HBV-DNA>10 IU/mL在T0时存在隐匿性HBV-DNA的PWH中占70%，仅HBV-RNA阳性者中占38.5%，两种HBV标志物均阴性者中占25%（P = 0.01）。T0时的隐匿性HBV-DNA和较低的CD4 + T细胞计数最低点独立预测T2时HBV-DNA>10 IU/mL（OR[95%CI]：8.2[1.7 - 40.6]，P = 0.01；OR[95%CI]：8.1[1.3 - 52.1]，P = 0.03）。最后，持续的HBV-DNA阳性与T2时CD4 + T细胞恢复降低独立相关（OR[95%CI]：0.07[0.01 - 0.77]，P = 0.03）。
本研究强调了对接受停用TDF/TAF方案的抗-HBc阳性/HBsAg阴性PWH进行定期监测的重要性，以及高灵敏度HBV标志物在优化其管理中的作用。
