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.
RCT Entities:
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: Christine J McGrath; Julia Njoroge; Grace C John-Stewart; Pamela K Kohler; Sarah F Benki-Nugent; Joan W Thiga; Anthony Etyang; Michael H Chung Journal: J Neurovirol Date: 2012-04-17 Impact factor: 2.643
Authors: Emily R Holzinger; Todd Hulgan; Ronald J Ellis; David C Samuels; Marylyn D Ritchie; David W Haas; Asha R Kallianpur; Cinnamon S Bloss; David B Clifford; Ann C Collier; Benjamin B Gelman; Christina M Marra; Justin C McArthur; J Allen McCutchan; Susan Morgello; David M Simpson; Donald R Franklin; Debralee Rosario; Doug Selph; Scott Letendre; Igor Grant Journal: J Neurovirol Date: 2012-10-17 Impact factor: 2.643
Authors: María Guzmán-Fulgencio; José Luis Jiménez; Mónica García-Álvarez; José María Bellón; Amanda Fernández-Rodriguez; Yolanda Campos; Carmen Rodríguez; Juan González-Garcia; Melchor Riera; Pompeyo Viciana; Ma Ángeles Muñoz-Fernández; Salvador Resino Journal: J Acquir Immune Defic Syndr Date: 2013-06-01 Impact factor: 3.731
Authors: Cm Shikuma; M Gerschenson; J Ananworanich; Vg Valcour; N Teeratakulpisarn; T Jadwattanakul; V Degruttola; C-Y Liang; Jc McArthur; Gj Ebenezer; N Chomchey; P Praihirunkit; P Hongchookiath; P Mathajittiphun; B Nakamoto; P Hauer; P Phanuphak; N Phanuphak Journal: HIV Med Date: 2012-05-11 Impact factor: 3.180
Authors: Todd Hulgan; David C Samuels; William Bush; Ronald J Ellis; Scott L Letendre; Robert K Heaton; Donald R Franklin; Peter Straub; Deborah G Murdock; David B Clifford; Ann C Collier; Benjamin B Gelman; Christina M Marra; Justin C McArthur; J Allen McCutchan; Susan Morgello; David M Simpson; Igor Grant; Asha R Kallianpur Journal: Clin Infect Dis Date: 2015-06-30 Impact factor: 20.999