Department of Medical Biotechnologies, University of Siena, Siena, Italy.
Department of Medicine, Johns Hopkins, University School of Medicine, Baltimore, MD.
J Acquir Immune Defic Syndr. 2022 Dec 1;91(4):381-389. doi: 10.1097/QAI.0000000000003073.
Clinical trials have demonstrated noninferior viral suppression rates of selected 2-drug regimens (2DRs) over standard 3-drug regimens (3DRs). However, the effect of simplification to 2DRs on HIV-1 reservoir remains to be fully assessed.
Retrospective analyses of samples of virologically suppressed people living with HIV remaining on the same 3DRs or switching to DTG + 3TC or ATV/r + 3TC 2DRs.
Whole blood samples were collected at enrollment and after 48 weeks. Total HIV-1 DNA (tDNA) and intact HIV-1 DNA (iDNA) were quantified by droplet digital polymerase chain reaction and intact proviral DNA assay, respectively. Statistical analysis was performed to identify associations among variables, and multiple linear regression was used to analyze potential predictors of tDNA and iDNA changes over time.
Forty-seven individuals were switched to DTG + 3TC 2DR (N = 23) and ATV/r + 3TC 2DR (N = 24), while 18 remained on 3DRs. tDNA did not change either in the overall population or in the 3DR and 2DR groups. iDNA decreased significantly in the whole data set and in the overall 3DR and 2DR groups ( P = 0.001, P = 0.039 and P = 0.009, respectively). iDNA, but not tDNA, was inversely correlated with the time of viral suppression ( P = 0.002) and time under antiretroviral therapy ( P = 0.006). Higher nadir CD4 + T-cell counts ( P = 0.001) and lower zenith viral load ( P = 0.02) showed an association with the decrease of iDNA, but not with tDNA.
Both tDNA and iDNA dynamics supported noninferior efficacy of 2DRs over 3DRs. iDNA could be more informative than tDNA in analyzing the dynamics of the HIV-1 reservoir under different treatment strategies.
临床试验已经证明,与标准三药治疗方案(3DRs)相比,某些二药治疗方案(2DRs)具有非劣效性的病毒抑制率。然而,简化为 2DRs 对 HIV-1 储存库的影响仍有待充分评估。
对仍在使用相同 3DRs 或改用 DTG+3TC 或 ATV/r+3TC 2DRs 的病毒学抑制的 HIV 感染者的样本进行回顾性分析。
在入组时和 48 周后采集全血样本。通过液滴数字聚合酶链反应和完整前病毒 DNA 测定分别定量检测总 HIV-1 DNA(tDNA)和完整 HIV-1 DNA(iDNA)。进行统计学分析以确定变量之间的关联,并使用多元线性回归分析随时间推移 tDNA 和 iDNA 变化的潜在预测因素。
47 人改用 DTG+3TC 2DR(N=23)和 ATV/r+3TC 2DR(N=24),而 18 人仍在使用 3DR。总体人群和 3DR 和 2DR 组的 tDNA 均未发生变化。整个数据集以及总体 3DR 和 2DR 组的 iDNA 均显著降低(P=0.001,P=0.039 和 P=0.009)。iDNA 与病毒抑制时间(P=0.002)和抗逆转录病毒治疗时间(P=0.006)呈负相关,但 tDNA 则不然。更低的 CD4+T 细胞计数(P=0.001)和更低的病毒载量峰值(P=0.02)与 iDNA 的降低相关,但与 tDNA 无关。
tDNA 和 iDNA 动力学均支持 2DRs 优于 3DRs 的疗效。与 tDNA 相比,iDNA 可能在分析不同治疗策略下 HIV-1 储存库的动态方面更具信息性。