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

Dhakshinamoorthy Subashini, Thongadi Ramesh Dinesha, Rao B. Srirama, Jayaseelan Boobalan, Selvamuthu Poongulali, Devaraj A. Chitra, Sarvode N. Mothi, Sunil Solomon, Shanmugam Saravanan, Suniti Solomon, Pachamuthu Balakrishnan

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)207-214
Number of pages8
JournalIndian Journal of Medical Research
Volume148
Issue number2
DOIs
StatePublished - Aug 1 2018

Fingerprint

Stavudine
Zidovudine
Mitochondrial DNA
Viruses
HIV-1
Blood Cells
Blood
HIV
Reverse Transcriptase Inhibitors
Toxicity
Nucleosides
Biomarkers
Therapeutics
Longitudinal Studies

Keywords

  • ART naïve
  • HIV
  • Mitochondrial DNA
  • Mitochondrial dysfunction
  • Nucleoside reverse transcriptase inhibitors
  • Peripheral blood mononuclear cells
  • Toxicity

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Subashini, D., Dinesha, T. R., Srirama, R. B., Boobalan, J., Poongulali, S., Chitra, D. A., ... Balakrishnan, P. (2018). Mitochondrial DNA content of peripheral blood mononuclear cells in ART untreated & stavudine/zidovudine treated HIV-1-infected patients. Indian Journal of Medical Research, 148(2), 207-214. https://doi.org/10.4103/ijmr.IJMR_1144_16

Mitochondrial DNA content of peripheral blood mononuclear cells in ART untreated & stavudine/zidovudine treated HIV-1-infected patients. / Subashini, Dhakshinamoorthy; Dinesha, Thongadi Ramesh; Srirama, Rao B.; Boobalan, Jayaseelan; Poongulali, Selvamuthu; Chitra, Devaraj A.; Mothi, Sarvode N.; Solomon, Sunil; Saravanan, Shanmugam; Solomon, Suniti; Balakrishnan, Pachamuthu.

In: Indian Journal of Medical Research, Vol. 148, No. 2, 01.08.2018, p. 207-214.

Research output: Contribution to journalArticle

Subashini, D, Dinesha, TR, Srirama, RB, Boobalan, J, Poongulali, S, Chitra, DA, Mothi, SN, Solomon, S, Saravanan, S, Solomon, S & Balakrishnan, P 2018, 'Mitochondrial DNA content of peripheral blood mononuclear cells in ART untreated & stavudine/zidovudine treated HIV-1-infected patients', Indian Journal of Medical Research, vol. 148, no. 2, pp. 207-214. https://doi.org/10.4103/ijmr.IJMR_1144_16
Subashini, Dhakshinamoorthy ; Dinesha, Thongadi Ramesh ; Srirama, Rao B. ; Boobalan, Jayaseelan ; Poongulali, Selvamuthu ; Chitra, Devaraj A. ; Mothi, Sarvode N. ; Solomon, Sunil ; Saravanan, Shanmugam ; Solomon, Suniti ; Balakrishnan, Pachamuthu. / Mitochondrial DNA content of peripheral blood mononuclear cells in ART untreated & stavudine/zidovudine treated HIV-1-infected patients. In: Indian Journal of Medical Research. 2018 ; Vol. 148, No. 2. pp. 207-214.
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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)-na{\"i}ve 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.",
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AU - Dinesha, Thongadi Ramesh

AU - Srirama, Rao B.

AU - Boobalan, Jayaseelan

AU - Poongulali, Selvamuthu

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AU - Mothi, Sarvode N.

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N2 - 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.

AB - 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.

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KW - HIV

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KW - Peripheral blood mononuclear cells

KW - Toxicity

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