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Epidermal nerve fiber density, oxidative stress, and mitochondrial haplogroups in HIV-infected Thais initiating therapy.
AIDS. 2014 Jul 17; 28(11):1625-33.AIDS

Abstract

OBJECTIVE

We explored associations between mitochondrial DNA (mtDNA) haplogroups, epidermal nerve fiber density (ENFD), and HIV-associated sensory neuropathy (HIV-SN) in a randomized trial of Thai patients initiating antiretroviral therapy (ART).

DESIGN

The South East Asia Research Collaboration with Hawaii 003 study evaluated toxicity of nucleoside reverse transcriptase inhibitors (stavudine vs. zidovudine vs. tenofovir). We present secondary analyses of mtDNA haplogroups and ENFD changes.

METHODS

ENFD, peripheral blood mononuclear cell mitochondrial complex I and IV, and 8-oxo-deoxyguanine (8-oxo-dG) were quantified. Peripheral blood mononuclear cell mtDNA sequences were obtained for haplogroup determination. Multivariate regression of ENFD change was performed.

RESULTS

Paired ENFD was available from 118 patients. Median age, CD4 cell count, and height at entry were 34 years, 172 cells/μl, and 162 cm, respectively. Major haplogroups included M (42%), F (21%), and B (16%). Baseline ENFD, CD4 cell count, randomized ART, and biomarkers did not differ by haplogroup. Haplogroup B patients were older (P=0.02) at baseline, and had an increase in median ENFD (+1.5 vs. -2.9 fibers/mm; P=0.03) and 8-oxo-dG break frequency (+0.05 vs. 0.00; P=0.05) compared to other haplogroups. In a multivariate model, haplogroup B was associated with increased ENFD (β=3.5, P=0.009) at week 24, whereas older age (P=0.02), higher baseline CD4 cell count, (P=0.03), higher complex I level (P=0.03), and higher ENFD (P<0.001) at baseline were all associated with decreased ENFD. Three of the six HIV-SN cases were haplogroup B (P=0.05).

CONCLUSIONS

Thai persons belonging to mtDNA haplogroup B had increased ENFD and 8-oxo-dG on ART, and were more likely to develop HIV-SN. These results suggest that mtDNA variation influences early oxidative damage and ENFD changes.

Authors+Show Affiliations

aVanderbilt University, Nashville, Tennessee bUniversity of Hawaii, Honolulu, Hawaii, USA cSouth East Asia Research Collaboration with Hawaii dThai Red Cross AIDS Research Centre eHIV-NAT, Bangkok fQueen Savang Vadhana Memorial Hospital, Chonburi, Thailand gThe Johns Hopkins University, Baltimore, Maryland, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Randomized Controlled Trial
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

24785954

Citation

Hulgan, Todd, et al. "Epidermal Nerve Fiber Density, Oxidative Stress, and Mitochondrial Haplogroups in HIV-infected Thais Initiating Therapy." AIDS (London, England), vol. 28, no. 11, 2014, pp. 1625-33.
Hulgan T, Levinson RT, Gerschenson M, et al. Epidermal nerve fiber density, oxidative stress, and mitochondrial haplogroups in HIV-infected Thais initiating therapy. AIDS. 2014;28(11):1625-33.
Hulgan, T., Levinson, R. T., Gerschenson, M., Phanuphak, N., Ananworanich, J., Teeratakulpisarm, N., Jadwattanakul, T., LiButti, D. E., Fink, H., McArthur, J. C., Ebenezer, G. J., Hauer, P., Murdock, D., Shikuma, C. M., & Samuels, D. C. (2014). Epidermal nerve fiber density, oxidative stress, and mitochondrial haplogroups in HIV-infected Thais initiating therapy. AIDS (London, England), 28(11), 1625-33. https://doi.org/10.1097/QAD.0000000000000297
Hulgan T, et al. Epidermal Nerve Fiber Density, Oxidative Stress, and Mitochondrial Haplogroups in HIV-infected Thais Initiating Therapy. AIDS. 2014 Jul 17;28(11):1625-33. PubMed PMID: 24785954.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Epidermal nerve fiber density, oxidative stress, and mitochondrial haplogroups in HIV-infected Thais initiating therapy. AU - Hulgan,Todd, AU - Levinson,Rebecca T, AU - Gerschenson,Mariana, AU - Phanuphak,Nittaya, AU - Ananworanich,Jintanat, AU - Teeratakulpisarm,Nipat, AU - Jadwattanakul,Tanate, AU - LiButti,Daniel E, AU - Fink,Heidi, AU - McArthur,Justin C, AU - Ebenezer,Gigi J, AU - Hauer,Peter, AU - Murdock,Deborah, AU - Shikuma,Cecilia M, AU - Samuels,David C, AU - ,, PY - 2014/5/3/entrez PY - 2014/5/3/pubmed PY - 2015/5/20/medline SP - 1625 EP - 33 JF - AIDS (London, England) JO - AIDS VL - 28 IS - 11 N2 - OBJECTIVE: We explored associations between mitochondrial DNA (mtDNA) haplogroups, epidermal nerve fiber density (ENFD), and HIV-associated sensory neuropathy (HIV-SN) in a randomized trial of Thai patients initiating antiretroviral therapy (ART). DESIGN: The South East Asia Research Collaboration with Hawaii 003 study evaluated toxicity of nucleoside reverse transcriptase inhibitors (stavudine vs. zidovudine vs. tenofovir). We present secondary analyses of mtDNA haplogroups and ENFD changes. METHODS: ENFD, peripheral blood mononuclear cell mitochondrial complex I and IV, and 8-oxo-deoxyguanine (8-oxo-dG) were quantified. Peripheral blood mononuclear cell mtDNA sequences were obtained for haplogroup determination. Multivariate regression of ENFD change was performed. RESULTS: Paired ENFD was available from 118 patients. Median age, CD4 cell count, and height at entry were 34 years, 172 cells/μl, and 162 cm, respectively. Major haplogroups included M (42%), F (21%), and B (16%). Baseline ENFD, CD4 cell count, randomized ART, and biomarkers did not differ by haplogroup. Haplogroup B patients were older (P=0.02) at baseline, and had an increase in median ENFD (+1.5 vs. -2.9 fibers/mm; P=0.03) and 8-oxo-dG break frequency (+0.05 vs. 0.00; P=0.05) compared to other haplogroups. In a multivariate model, haplogroup B was associated with increased ENFD (β=3.5, P=0.009) at week 24, whereas older age (P=0.02), higher baseline CD4 cell count, (P=0.03), higher complex I level (P=0.03), and higher ENFD (P<0.001) at baseline were all associated with decreased ENFD. Three of the six HIV-SN cases were haplogroup B (P=0.05). CONCLUSIONS: Thai persons belonging to mtDNA haplogroup B had increased ENFD and 8-oxo-dG on ART, and were more likely to develop HIV-SN. These results suggest that mtDNA variation influences early oxidative damage and ENFD changes. SN - 1473-5571 UR - https://www.unboundmedicine.com/medline/citation/24785954/Epidermal_nerve_fiber_density_oxidative_stress_and_mitochondrial_haplogroups_in_HIV_infected_Thais_initiating_therapy_ L2 - https://doi.org/10.1097/QAD.0000000000000297 DB - PRIME DP - Unbound Medicine ER -