未接受抗逆转录病毒治疗和接受司他夫定/齐多夫定治疗的 HIV-1 感染患者外周血单个核细胞中线粒体 DNA 含量。

Mitochondrial DNA content of peripheral blood mononuclear cells in ART untreated & stavudine/zidovudine treated HIV-1-infected patients.

机构信息

Infectious Diseases Laboratory, Y.R. Gaitonde Centre for AIDS Research & Education, Voluntary Health Services Hospital Campus, Chennai, India.

Department of Infectious Diseases, Asha Kirana Hospital, Mysore, India.

出版信息

Indian J Med Res. 2018 Aug;148(2):207-214. doi: 10.4103/ijmr.IJMR_1144_16.

DOI:10.4103/ijmr.IJMR_1144_16

PMID:30381544

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6206766/

Abstract

BACKGROUND & OBJECTIVES: Nucleoside reverse transcriptase inhibitors (NRTIs) are known to cause mitochondrial toxicity. This study was done to estimate mitochondrial DNA (mtDNA) content of peripheral blood mononuclear cells (PBMCs) among human immunodeficiency virus (HIV) infected, NRTI treated and antiretroviral therapy (ART)-naïve patients and evaluate the utility of mtDNA content as a biomarker of mitochondrial toxicity.

METHODS

mtDNA content in PBMCs of 57 HIV-infected ART untreated and 30 ART treated with stavudine (d4T) or zidovudine (AZT) containing regimen were compared against 24 low-risk healthy controls (LoRHC).

RESULTS

There was a significant (P=0.01) reduction in mtDNA content among HIV-infected (104; 80-135) compared to LoRHC (127; 110-167), and it was the same in both the treated (104.8; 88-130) and untreated patients (104.7; 78-142). mtDNA significantly (P=0.014) declined in ART treated patients symptomatic for toxicity (97; 74-111) than the asymptomatic patients (128; 103- 153).

INTERPRETATION & CONCLUSIONS: mtDNA depletion in PBMCs was evident among HIV-infected individuals on ART. Moreover, as mtDNA content was reduced among the patients symptomatic for toxicity than the asymptomatic in both the HIV-infected groups, the current study supports mtDNA content of PBMCs to serve as a biomarker of mitochondrial dysfunction induced by NRTI and HIV. Longitudinal studies with a large sample need to be done to confirm these findings.

摘要

背景与目的

核苷逆转录酶抑制剂（NRTIs）已知会引起线粒体毒性。本研究旨在评估人类免疫缺陷病毒（HIV）感染、NRTI 治疗且未接受抗逆转录病毒治疗（ART）的患者外周血单个核细胞（PBMC）中的线粒体 DNA（mtDNA）含量，并评估 mtDNA 含量作为线粒体毒性生物标志物的效用。

方法

比较了 57 例未经 ART 治疗的 HIV 感染患者和 30 例接受包含司他夫定（d4T）或齐多夫定（AZT）的 ART 治疗的患者的 PBMC 中的 mtDNA 含量与 24 例低风险健康对照者（LoRHC）。

结果

与 LoRHC（127；110-167）相比，HIV 感染患者（104；80-135）的 mtDNA 含量显著降低（P=0.01），且在治疗组（104.8；88-130）和未治疗组（104.7；78-142）中均如此。在有 NRTI 毒性症状的 ART 治疗患者中（97；74-111），mtDNA 显著降低（P=0.014），而无症状患者（128；103-153）中则没有。

结论

在接受 ART 的 HIV 感染者中，PBMC 中的 mtDNA 耗竭是显而易见的。此外，由于在两组 HIV 感染患者中，有 NRTI 毒性症状的患者的 mtDNA 含量均低于无症状患者，因此本研究支持 PBMC 的 mtDNA 含量可作为 NRTI 和 HIV 诱导的线粒体功能障碍的生物标志物。需要进行更多大样本的纵向研究来证实这些发现。