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NRTIs’ effect on the sequence of mitochondrial DNA HV 2 in HIV infected patients

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Abstract

Potent combination antiretroviral therapy (cART) has significantly improved the life expectancy of people living with human immunodeficiency virus (HIV), but it has many side effects such as lipodystrophy (LD), hepatic steatosis, and lactic acidosis. Nucleoside reverse transcriptase inhibitors (NRTIs) could damage the mitochondria by inhibiting the human DNA polymerase gamma, leading to mtDNA deletion. However, it remains uncertain whether NRTIs could induce the hypervariable region (HV) mutations of the D loop of mitochondria in Chinese HIV/AIDS patients, and whether that effect is different between individuals with and without LD. Hereby, 30 Chinese AIDS patients who were receiving antiretroviral drugs were recruited, among which 16 had symptomatic LD and 14 did not. Blood samples were collected prior to and after 96 weeks of treatment. Total DNA was extracted from peripheral blood mononuclear cells (PBMCs). Fragments of 728 bp in length containing HV2 were amplified by standard polymerase chain reaction (PCR). Direct DNA-sequencing analysis techniques were used to detect mitochondrial sequence variants between paired longitudinal samples. Alterations were compared with the revised Cambridge Reference Sequence (rCRS) to determine mutation or polymorphism. Results showed that two years after ART, totally seven cases exhibited sequence variations, ve individuals showed 73 → G revised variation (two with and three without LD), while two cases of LD were found to have other nucleotide alterations. There was no new alteration in individuals without LD. In conclusion, NRTIs could induce mutation of mtDNA HV2, which might contribute to the development of LD.

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Authors and Affiliations

  1. Division of Treatment and Care, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, 102206, China

    Ya-Song Wu & Fu-Jie Zhang

  2. Center for Infectious Diseases, Beijing You’an Hospital, Capital Medical University, Beijing, 100069, China

    Xin-Yue Chen, Ying Shi, Hao Wu, De-Xi Chen & Yu Sun

  3. Beijing Ditan Hospital, Beijing, 100015, China

    Fu-Jie Zhang

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  1. Ya-Song Wu
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  2. Xin-Yue Chen
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  4. Hao Wu
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Correspondence to Hao Wu.

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Wu, YS., Chen, XY., Shi, Y. et al. NRTIs’ effect on the sequence of mitochondrial DNA HV 2 in HIV infected patients. Front. Med. China 4, 177–184 (2010). https://doi.org/10.1007/s11684-010-0038-1

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  • DOI: https://doi.org/10.1007/s11684-010-0038-1

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