摘要目的 研究高效联合抗反转录病毒治疗(HAART)过程中外周血单核淋巴细胞(PBMC)内线粒体DNA(mtDNA)含量变化规律及其与人类免疫缺陷病毒(HIV)感染相关脂肪营养不良(HIV-LD)的相关性.方法 通过实时定量PCR(real-time PCR),对2002年5月至2008年5月北京协和医院感染内科门诊长期规律随访的33例HIV/AIDS中国成年患者抗病毒治疗基线、半年、2年的mtDNA含量测定,其中出现了HIV-LD的为17例,比较各组间的差异.结果 HIV/AIDS患者治疗基线PBMC mtDNA含量低于健康对照组(9.578比17.195,P＜0.01).HIV-LD组治疗各时点PBMCmtDNA含量均显著低于未出现脂肪营养不良综合征(NLD)组(治疗基线、治疗半年、治疗2年分别为13.619比5.775、6.360比1.387、7.170比1.266).mtDNA含量降低先于临床HIV-LD的出现.使用司他夫定(d4T)方案组患者PBMC mtDNA含量(2-△△Ct)治疗后较基线显著降低,而齐多夫定(AZT)方案组患者治疗前后PBMC mtDNA含量变化不显著(P=0.205).结论 HIV感染和d4T与PBMCmtDNA含量的下降具有密切关系.

abstractsObjective To investigate the change regularity of peripheral blood mononuclear cell ( PBMC) mtDNA ( mitochondrial deoxyribonucleic acid) content and its association with HIV-LD ( human immunodeficiency virus-related lipodystrophy ) in HAART ( highly active antiretroviral therapy). Methods At baseline, Months 6 and 24 of therapy, the cryopreserved PBMC were collected from 33 patients on a regular follow-up at our clinic. Among them, 17 had HIV-LD. Then total DNA was extracted and mtDNA content quantified by real-time PCR (polymerase chain reaction). Results The HIV/AIDS patients had a lower content of PBMC mtDNA (2-△△Ct) than the healthy controls at baseline (9.578 vs 17. 195, P ＜0.01). The mtDNA content was lower in the HIV-LD group than that in the no LD (NLD) group at each timepoint of therapy (13.619 vs5.775, 6.360 vs 1.387, 7. 170 vs 1.266, all P＜0.05). In the HIV-LD group, the half- and 2-year PBMC mtDNA content was markedly lower than those at baseline (both P ＜0. 05 ). And the change of mtDNA content (within half a year) was earlier than the onset of clinical HIV-LD at one year later. In the NLD group, the PBMC mtDNA content have an insignificant change after therapy.The mtDNA content decreased significantly in stavudine (d4T)-containing regimen group after treatment (P ＜0. 01) , but showed no significant change in zidovudine ( AZT) -containing regimen group after therapy.Conclusion The decreased content of PBMC mtDNA after HIV infection and during HAART therapy is associated with HIV-LD. Nucleoside reverse transcriptase inhibitor, especially d4T, plays an important role in the progression of HIV-LD.