Title | T cell activation markers and African mitochondrial DNA haplogroups among non-Hispanic black participants in AIDS clinical trials group study 384. |
Publication Type | Journal Article |
Year of Publication | 2012 |
Authors | Hulgan T, Robbins GK, Kalams SA, Samuels DC, Grady B, Shafer R, Murdock DG, Selph D, Haas DW, Pollard RB |
Corporate Authors | AIDS Clinical Trials Group |
Journal | PLoS One |
Volume | 7 |
Issue | 8 |
Pagination | e43803 |
Date Published | 2012 |
ISSN | 1932-6203 |
Keywords | Acquired Immunodeficiency Syndrome, Adult, African Americans, Anti-HIV Agents, CD4-CD8 Ratio, DNA, Mitochondrial, Female, Gene Frequency, Haplotypes, HIV-1, Humans, Linear Models, Lymphocyte Activation, Male, Middle Aged, Multivariate Analysis, Randomized Controlled Trials as Topic, RNA, Viral, Sequence Analysis, DNA, Statistics, Nonparametric, T-Lymphocytes, Viral Load |
Abstract | INTRODUCTION: Mitochondrial function influences T cell dynamics and is affected by mitochondrial DNA (mtDNA) variation. We previously reported an association between African mtDNA haplogroup L2 and less robust CD4 cell recovery on antiretroviral therapy (ART) in non-Hispanic black ACTG 384 subjects. We explored whether additional T cell parameters in this cohort differed by mtDNA haplogroup. METHODS: ACTG 384 randomized ART-naïve subjects to two different nucleoside regimens with efavirenz, nelfinavir, or both. CD4 and CD8 memory and activation markers were available at baseline and week 48 on most subjects. mtDNA sequencing was performed on whole blood DNA, and haplogroups were determined. We studied non-Hispanic black subjects with HIV RNA <400 copies/mL at week 48. Analyses included Wilcoxon ranksum test and linear regression. RESULTS: Data from 104 subjects were included. Major African mtDNA haplogroups included L1 (N=25), L2 (N=31), and L3 (N=32). Baseline age, HIV RNA, and CD4 cells did not differ between L2 and non-L2 haplogroups. Compared to non-L2 haplogroups, L2 subjects had lower baseline activated CD4 cells (median 12% vs. 17%; p=0.03) and tended toward lower activated CD8 cells (41% vs. 47%; p=0.06). At 48 weeks of ART, L2 subjects had smaller decreases in activated CD4 cells (-4% vs. -11%; p=0.01), and smaller CD4 cell increases (+95 vs. +178; p=0.002). In models adjusting for baseline age, CD4 cells, HIV RNA, and naïve-to-memory CD4 cell ratio, haplogroup L2 was associated with lower baseline (p=0.04) and 48-week change in (p=0.01) activated CD4 cells. CONCLUSIONS: Among ART-naïve non-Hispanic blacks, mtDNA haplogroup L2 was associated with baseline and 48-week change in T cell activation, and poorer CD4 cell recovery. These data suggest mtDNA variation may influence CD4 T cell dynamics by modulating T cell activation. Further study is needed to replicate these associations and identify mechanisms. |
DOI | 10.1371/journal.pone.0043803 |
Alternate Journal | PLoS ONE |
PubMed ID | 22970105 |
PubMed Central ID | PMC3433792 |
Grant List | 5T32GM80178 / GM / NIGMS NIH HHS / United States AI062435 / AI / NIAID NIH HHS / United States AI069415 / AI / NIAID NIH HHS / United States AI069419 / AI / NIAID NIH HHS / United States AI069423 / AI / NIAID NIH HHS / United States AI069424 / AI / NIAID NIH HHS / United States AI069428 / AI / NIAID NIH HHS / United States AI069432 / AI / NIAID NIH HHS / United States AI069434 / AI / NIAID NIH HHS / United States AI069450 / AI / NIAID NIH HHS / United States AI069452 / AI / NIAID NIH HHS / United States AI069465 / AI / NIAID NIH HHS / United States AI069471 / AI / NIAID NIH HHS / United States AI069472 / AI / NIAID NIH HHS / United States AI069474 / AI / NIAID NIH HHS / United States AI069477 / AI / NIAID NIH HHS / United States AI069484 / AI / NIAID NIH HHS / United States AI069495 / AI / NIAID NIH HHS / United States AI069501 / AI / NIAID NIH HHS / United States AI069502 / AI / NIAID NIH HHS / United States AI069511 / AI / NIAID NIH HHS / United States AI069513 / AI / NIAID NIH HHS / United States AI069532 / AI / NIAID NIH HHS / United States AI069556 / AI / NIAID NIH HHS / United States AI077505 / AI / NIAID NIH HHS / United States AI25859 / AI / NIAID NIH HHS / United States AI27661 / AI / NIAID NIH HHS / United States AI34835 / AI / NIAID NIH HHS / United States AI34853 / AI / NIAID NIH HHS / United States AI38844 / AI / NIAID NIH HHS / United States AI38858 / AI / NIAID NIH HHS / United States AI46370 / AI / NIAID NIH HHS / United States AI54999 / AI / NIAID NIH HHS / United States AI69467 / AI / NIAID NIH HHS / United States AI69495 / AI / NIAID NIH HHS / United States AL32782 / / PHS HHS / United States HL087726 / HL / NHLBI NIH HHS / United States NS059330 / NS / NINDS NIH HHS / United States R21 NS059330 / NS / NINDS NIH HHS / United States U01AI068636 / AI / NIAID NIH HHS / United States UL1 TR000445 / TR / NCATS NIH HHS / United States UM1 AI069477 / AI / NIAID NIH HHS / United States |