来自HIV-1感染且病毒学抑制个体的外周血单个核细胞（PBMC）基因型耐药性检测中耐药性和APOBEC编辑的时间趋势。

Temporal trend of drug-resistance and APOBEC editing in PBMC genotypic resistance tests from HIV-1 infected virologically suppressed individuals.

作者信息

Armenia D, Gagliardini R, Alteri C, Svicher V, Cento V, Borghi V, Vergori A, Cicalini S, Forbici F, Fabeni L, Bertoli A, Brugneti M, Gennari W, Malagnino V, Andreoni M, Mussini C, Antinori A, Perno C F, Santoro M M, Ceccherini-Silberstein F

机构信息

UniCamillus, Saint Camillus International University of Health Sciences, Rome, Italy.

National Institute for Infectious Diseases L. Spallanzani, IRCCS, Rome, Italy.

出版信息

J Clin Virol. 2023 Nov;168:105551. doi: 10.1016/j.jcv.2023.105551. Epub 2023 Jul 23.

DOI:10.1016/j.jcv.2023.105551

PMID:37573167

Abstract

BACKGROUND

We aimed at evaluating the temporal trend of drug-resistance and APOBEC editing from HIV-DNA genotypic resistance tests (GRT) in virologically suppressed individuals.

MATERIAL AND METHODS

Major resistance mutations (MRM), genotypic susceptibility score (GSS) for the current regimen and APOBEC-related mutations (APO-M) were evaluated. Potential changes in trends of MRM and APO-M over-time were assessed and predictors of MRM detection or sub-optimal GSS (GSS<2) at HIV-DNA-GRT were estimated through logistic regression analyses.

RESULTS

Among the 1126 individuals included, 396 (35.2%) harboured at least one MRM (23.4% to NRTI, 18.8% to NNRTI, 7.7% to PI and 1.4% to INSTI [N=724]); 132 (12.3%) individuals showed a GSS <2. APO-M and stop codons were found in 229 (20.3%) and 105 (9.3%) individuals, respectively. APO-DRMs were found in 16.8% of individuals and were more likely observed in those individuals with stop codons (40.0%) compared to those without (14.4%, P<0.001). From 2010 to 2021 no significant changes of resistance or APO-M were found. Positive predictors of MRM detection at HIV-DNA GRT were drug abuse, subtype B infection, and a prolonged and complex treatment history. Perinatal infection and having at least 2 stop codons were associated with a current suboptimal regimen.

CONCLUSIONS

In virologically suppressed individuals, resistance in HIV-DNA and the extent of APOBEC editing were generally stable in the last decade. A careful evaluation of APOBEC editing might be helpful to improve the reliability of HIV-DNA GRT. Further investigations are required to understand how to apply the estimation of APOBEC editing in refining genotypic evaluation.

摘要

背景

我们旨在评估病毒学抑制个体中HIV-DNA基因型耐药性检测（GRT）的耐药性和APOBEC编辑的时间趋势。

材料与方法

评估主要耐药突变（MRM）、当前治疗方案的基因型易感性评分（GSS）和APOBEC相关突变（APO-M）。评估MRM和APO-M随时间变化趋势的潜在变化，并通过逻辑回归分析估计HIV-DNA-GRT检测到MRM或次优GSS（GSS<2）的预测因素。

结果

在纳入的1126名个体中，396名（35.2%）至少携带一种MRM（核苷类逆转录酶抑制剂为23.4%，非核苷类逆转录酶抑制剂为18.8%，蛋白酶抑制剂为7.7%，整合酶链转移抑制剂为1.4%[N=724]）；132名（12.3%）个体的GSS<2。分别在229名（20.3%）和105名（9.3%）个体中发现了APO-M和终止密码子。在16.8%的个体中发现了APO-DRM，与没有终止密码子的个体（14.4%，P<0.001）相比，在有终止密码子的个体中更易观察到（40.0%）。从2010年到2021年，未发现耐药性或APO-M有显著变化。HIV-DNA GRT检测到MRM的阳性预测因素是药物滥用、B亚型感染以及长期复杂的治疗史。围产期感染和至少有2个终止密码子与当前的次优治疗方案相关。