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一种非核苷类逆转录酶抑制剂替代一种核苷类似物对线粒体DNA水平的影响。

Effect of the substitution of one nucleoside analogue by one non-nucleoside reverse transcriptase inhibitor over mitochondrial DNA levels.

作者信息

De Felipe B, Blanco A, Soriano-Sarabia N, Muñoz-Fernández M A, Genebat M, Vallejo A, Leal M

机构信息

Service of Infectious Diseases, Virgen del Rocío University Hospital, Seville, Spain.

出版信息

Infection. 2008 Jun;36(3):266-70. doi: 10.1007/s15010-008-7312-z. Epub 2008 May 3.

Abstract

BACKGROUND

Long-term antiretroviral therapy is associated with several side effects, like mitochondrial toxicity related to nucleoside reverse transcriptase inhibitors (NRTIs). Our objective was to analyze the effect of the substitution of one NRTI by one non-nucleoside reverse transcriptase inhibitor (NNRTI) in the antiretroviral regime of HIV-1-infected patients who were on a regime containing either two NRTIs and one NNRTI, or one NRTI, one NNRTI and one protease inhibitor (PI), over mtDNA level. Decreasing NRTIs could increase mtDNA level.

METHODS

Fifteen HIV-1-infected patients were included in the study. As controls, 17 healthy individuals and 15 HIV-1-infected patients naïve for antiretroviral treatment were also analyzed. mtDNA level was quantified at baseline and after 48 weeks of treatment.

RESULTS

Control groups showed higher levels of mtDNA than the study group (p<0.001). Among this latter group, no statistical differences between baseline and after 48 weeks were found. Naïve HIV-infected patients had lower mtDNA than healthy volunteers (p<0.001). Two patients had two consecutive blips (low viral load increases) but they did not show NNRTI-related resistance mutations.

CONCLUSIONS

This study shows that although this treatment was immunovirologically effective, mtDNA level did not increase at least after 48 weeks.

摘要

背景

长期抗逆转录病毒治疗会引发多种副作用,比如与核苷类逆转录酶抑制剂(NRTIs)相关的线粒体毒性。我们的目标是分析在接受包含两种NRTIs和一种非核苷类逆转录酶抑制剂(NNRTIs),或一种NRTI、一种NNRTI和一种蛋白酶抑制剂(PI)治疗方案的HIV-1感染患者的抗逆转录病毒治疗方案中,用一种NNRTI替代一种NRTI对线粒体DNA(mtDNA)水平的影响。减少NRTIs可能会提高mtDNA水平。

方法

15名HIV-1感染患者被纳入研究。作为对照,还分析了17名健康个体和15名未接受过抗逆转录病毒治疗的HIV-1感染患者。在基线期和治疗48周后对mtDNA水平进行定量分析。

结果

对照组的mtDNA水平高于研究组(p<0.001)。在研究组中,基线期和48周后未发现统计学差异。未接受过治疗的HIV感染患者的mtDNA水平低于健康志愿者(p<0.001)。两名患者出现了两次连续的病毒载量小幅上升(低病毒载量增加),但未显示出与NNRTI相关的耐药突变。

结论

本研究表明,尽管该治疗在免疫病毒学方面有效,但至少在48周后mtDNA水平并未升高。

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