Alteri Claudia, Scutari Rossana, Bertoli Ada, Armenia Daniele, Gori Caterina, Fabbri Gabriele, Mastroianni Claudio Maria, Cerva Carlotta, Cristaudo Antonio, Vicenti Ilaria, Bruzzone Bianca, Zazzi Maurizio, Andreoni Massimo, Antinori Andrea, Svicher Valentina, Ceccherini-Silberstein Francesca, Perno Carlo Federico, Santoro Maria Mercedes
Department of Experimental Medicine and Surgery, University of Rome "Tor Vergata", Via Montpellier 1, 00133, Rome, Italy.
Department of Oncology and Hemato-Oncology, University of Milan, Via Festa del Perdono 7, 20122, Milano, Italia.
Virus Genes. 2019 Jun;55(3):290-297. doi: 10.1007/s11262-019-01649-z. Epub 2019 Feb 22.
Integrase-strand-transfer inhibitors (INSTIs) are known to rapidly reduce HIV-1 plasma viral load, replication cycles, and new viral integrations, thus potentially limiting viral evolution. Here, we assessed the role of INSTIs on HIV-1 V3 evolution in a cohort of 89 HIV-1-infected individuals starting an INSTI- (N = 41, [dolutegravir: N = 1; elvitegravir: N = 3; raltegravir: N = 37]) or a non-INSTI-based (N = 48) combined antiretroviral therapy (cART), with two plasma RNA V3 genotypic tests available (one before [baseline] and one during cART). V3 sequences were analysed for genetic distance (Tajima-Nei model) and positive selection (dN/dS ratio). Individuals were mainly infected by B subtype (71.9%). Median (interquartile-range, IQR) plasma viral load and CD4 + T cell count at baseline were 4.8 (3.5-5.5) log copies/mL and 207 (67-441) cells/mm, respectively. Genetic distance (median, IQR) between the V3 sequences obtained during cART and those obtained at baseline was 0.04 (0.01-0.07). By considering treatment, genetic distance was significantly lower in INSTI-treated than in non-INSTI-treated individuals (median [IQR]: 0.03[0.01-0.04] vs. 0.05[0.02-0.08], p = 0.026). In line with this, a positive selection (defined as dN/dS ≥ 1) was observed in 36.6% of V3 sequences belonging to the INSTI-treated group and in 56.3% of non-INSTI group (p = 0.05). Multivariable logistic regression confirmed the independent correlation of INSTI-based regimens with a lower probability of both V3 evolution (adjusted odds-ratio: 0.35 [confidence interval (CI) 0.13-0.88], p = 0.027) and positive selection (even if with a trend) (adjusted odds-ratio: 0.46 [CI 0.19-1.11], p = 0.083). Overall, this study suggests a role of INSTI-based regimen in limiting HIV-1 V3 evolution over time. Further studies are required to confirm these findings.
整合酶链转移抑制剂（INSTIs）已知可迅速降低HIV-1血浆病毒载量、复制周期和新的病毒整合，从而有可能限制病毒进化。在此，我们评估了INSTIs对89名开始接受基于INSTI（N = 41，[多替拉韦：N = 1；埃替拉韦：N = 3；拉替拉韦：N = 37]）或非INSTI的（N = 48）联合抗逆转录病毒疗法（cART）的HIV-1感染者队列中HIV-1 V3进化的作用，有两次血浆RNA V3基因型检测可用（一次在[基线]之前，一次在cART期间）。分析V3序列的遗传距离（田岛-内模型）和正选择（dN/dS比率）。个体主要感染B亚型（71.9%）。基线时血浆病毒载量和CD4 + T细胞计数的中位数（四分位间距，IQR）分别为4.8（3.5 - 5.5）log拷贝/mL和207（67 - 441）个细胞/mm³。cART期间获得的V3序列与基线时获得的V3序列之间的遗传距离（中位数，IQR）为0.04（0.01 - 0.07）。考虑治疗因素，接受INSTI治疗的个体的遗传距离显著低于未接受INSTI治疗的个体（中位数[IQR]：0.03[0.01 - 0.04]对0.05[0.02 - 0.08]，p = 0.026）。与此一致的是，在接受INSTI治疗组的36.6%的V3序列和非INSTI组的56.3%的V3序列中观察到正选择（定义为dN/dS≥1）（p = 0.05）。多变量逻辑回归证实基于INSTI的治疗方案与较低的V3进化概率（调整后的优势比：0.35[置信区间（CI）0.13 - 0.88]，p = 0.027）和正选择（即使有趋势）（调整后的优势比：0.46[CI 0.19 - 1.11]，p = 0.083）均独立相关。总体而言，本研究表明基于INSTI的治疗方案在限制HIV-1 V3随时间进化方面的作用。需要进一步研究来证实这些发现。
