European mitochondrial DNA haplogroups and metabolic changes during antiretroviral therapy in AIDS Clinical Trials Group Study A5142*
Year: 2010
Type: article
Abstract: BACKGROUND: Mitochondrial DNA (mtDNA) influences metabolic diseases and perhaps antiretroviral therapy (ART) complications. We explored associations between European mtDNA haplogroups and metabolic changes among A5142 participants. METHODS: Seven hundred and fifty-seven ART-naive patients were randomized to one of three class-sparing ART regimens including efavirenz and/or lopinavir/ritonavir with or without nucleoside reverse transcriptase inhibitors (NRTIs). Nonrandomized NRTIs included stavudine, tenofovir, or zidovudine, each with lamivudine. Fasting lipid profiles and whole-body dual-energy X-ray absorptiometry (DEXA) were performed. Nine European mtDNA haplogroups were determined for 231 self-identified non-Hispanic white individuals. Metabolic changes from baseline to 96 weeks were analyzed by haplogroup. RESULTS: Median age was 39 years, 9% were women, and 37, 32, and 30 were randomized to NRTI-containing regimens with either efavirenz or lopinavir/ritonavir, and an NRTI-sparing regimen, respectively. Among NRTI-containing regimens, 51% included zidovudine, 28% tenofovir, and 21% stavudine. Compared with other haplogroups, mtDNA haplogroup I (N = 10) had higher baseline non-HDL cholesterol [160 mg/dl (interquartile range 137-171) vs. 120 mg/dl (104-136); P = 0.005], a decrease in non-HDL cholesterol over 96 weeks [-14% (-20 to 6) vs. +25% (8 to 51); P < 0.001], tended to have more baseline extremity fat, and had more extremity fat loss by DEXA [-13% (-13 to 12) vs. +9% (-13 to 26); P = 0.08] and lipoatrophy (50 vs. 20%; P = 0.04). Haplogroup W (N = 5; all randomized to NRTI-sparing regimens) had the greatest increase in extremity fat [+35.5% (26.8 to 54.9); P = 0.02]. CONCLUSIONS: Lipids and extremity fat were associated with European mtDNA haplogroups in this HIV-infected population. These preliminary results suggest that mitochondrial genomics may influence metabolic parameters before and during ART.
Source: AIDS
Language: English
Subfield: Emergency Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: G101757908, G1033683653, G1065691059, G1068660208, G1143685601, The Ohio State University AIDS Clinical Trials Unit, G123932167, G1276011396, University of Cincinnati AIDS Clinical Trials Unit- UC ACTU, WASHINGTON UNIVERSITY AIDS CLINICAL TRIALS UNIT, The Ohio State University AIDS Clinical Trials Unit, G1339061363, New York University HIV/AIDS Clinical Trial Unit, G1346130624, Atlanta Clinical and Translational Science Institute (UL1), G1479152345, Stanford AIDS Clinical Trials Unit, G1534260048, G154087045, G1586133245, G161582775, UW Clinical HIV Integrated Research Program, Emory HIV/AIDS Clinical Trials Unit, WASHINGTON UNIVERSITY AIDS CLINICAL TRIALS UNIT, G1681955143, Chinese Clinical Trials Unit for HIV Research (CCTU), G174905615, U.T. SOUTHWESTERN ADULT AIDS CLINICAL TRIALS UNIT, G1805005405, G1819583291, G1840998190, G185513119, Vanderbilt HIV Clinical Trials Unit, G1939027404, G1939689254, G1944963898, G2069435444, Role of Mitochondria in HIV Lipoatrophy, G2135258891, G2199452652, G2220623200, G229144670, G2368841045, G2381598486, G2398866917, Miami HIV/AIDS Clinical Therapeutic and Vaccine Trial Unit, G2507544392, G251702431, G2682253789, G2709153970, University of North Carolina AIDS Clinical Trials Unit (UNC ACTU), ADULT AIDS CLINICAL TRIALS UNIT, G299859194, G3116536149, Cornell Clinical Trials Unit, MODEL DEVELOPMENT FOR MATERNAL/FETAL TRANSMISSION OF HIV, G3206835426, G3206931443, G3277483280, Johns Hopkins AIDS Clinical Trials Unit, Role of Mitochondria in HIV Lipoatrophy, General Clinical Research Center, ADULT AIDS CLINICAL TRIALS UNIT (ACTU), G3525517067, Miami Treatment and Prevention Clinical Trials Unit (CTU), AIDS Clinical Trials Group Network, Alabama-Clinical Trials Unit, G367367271, G373348672, UCLA AIDS Prevention and Treatment Clinical Trials Unit, G3788978964, UW Clinical HIV Integrated Research Program, G3810609436, G3873853564, General Clinical Research Center, ADULT AIDS CLINICAL TRIALS UNIT, G4122054131, GENERAL CLINICAL RESEARCH CENTER, General Clinical Research Center, G4166928756, General Clinical Research Center, G4205250407, General Clinical Research Center, G4316068824, G4317913406, Northwestern University Clinical Trial Unit, Colorado AIDS Clinical Trials Unit, Institute of Human Virology Clinical Trials Unit, G473273920, Case Clinical Trials Unit, Stanford AIDS Clinical Trials Unit, General Clinical Research Center, University of Pittsburgh Clinical Trials Unit, G517861501, ADULT THERAPEUTIC CLINICAL TRIALS PROGRAM IN AIDS, UCSF HIV Clinical Trials Unit, New York University HIV/AIDS Clinical Trial Unit, ADULT ACTG CENTRAL GROUP, Improving Antiretroviral Management for HIV, G563474107, Statistical and Data Management Center for the AIDS Clinical Trials Group, UCSD Department of Medicine HIV/AIDS Clinical Trials Unit, The Vanderbilt Institute for Clinical and Translational Research (VICTR) KL2, HIV/AIDS Clinical Trial Unit in NCAIDS, China CDC, General Clinical Research Center, G5937357401, Atlanta Clinical and Translational Science Institute (ACTSI) Renewal, G602580346, Case AIDS Clinical Trials Unit, The Vanderbilt Institute for Clinical and Translational Research (VICTR) TL1, GENERAL CLINICAL RESEARCH CENTER, ADULT AIDS CLINICAL TRIAL UNIT, G6103943158, Partners Healthcare Systems/Harvard Medical School/Boston Medical Center AIDS CTU, The Vanderbilt Institute for Clinical and Translational Research (VICTR) UL1, University of Cincinnati AIDS Clinical Trials Unit- UC ACTU, Colorado AIDS Clinical Trials Unit, UCSF HIV Clinical Trials Unit, AIDS CLINICAL TRIALS UNIT, Partners Healthcare Systems/Harvard Medical School/Boston Medical Center AIDS CTU, Columbia Collaborative HIV/AIDS Clinical Trials Unit, G7348756, G7403049968, HAWAII ACTU - ADULT THERAPEUTIC CLINICAL TRIALS PROGRAM, G749807406, HIV/AIDS Clinical Trials Unit, HIV/AIDS Clinical Trials Unit, AIDS RESEARCH, Institute of Human Virology Clinical Trials Unit, ADULT THERAPEUTIC CLINICAL TRIALS PROGRAM FOR HIV/AIDS, UCSD Collaborative Clinical Trials Unit, Weill Cornell Medicine - Rutgers New Jersey Medical School Clinical Trials Unit, Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections, Emory-CDC CTU, Chicago Clinical Trials Unit, San Diego Center for AIDS Research (SD CFAR), Statistical and Data Management Center (SDMC), Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections (ACTG), Penn Center for AIDS Research, Johns Hopkins University Baltimore India Clinical Trail Unit (JHUBI CTU), The University of North Carolina Center for AIDS Research, Pitt-Ohio State Clinical Trials Unit, Columbia Collaborative HIV/AIDS Clinical Trials Unit, University of North Carolina Global HIV Prevention and Treatment Clinical Trials Unit, Harvard University Center for AIDS Research, UCLA AIDS Prevention and Treatment Clinical Trials Unit, Vanderbilt HIV Clinical Trials Unit (CTU), A-Z Clinical Trials Unit, G939730012, G964886957
OpenAlex ID: W2022166810