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T cell activation markers and African mitochondrial DNA haplogroups among non-Hispanic black participants in AIDS clinical trials group study 384.
PLoS One. 2012; 7(8):e43803.Plos

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.

Authors+Show Affiliations

Vanderbilt University School of Medicine, Nashville, Tennessee, USA. todd.hulgan@vanderbilt.eduNo 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
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22970105

Citation

Hulgan, Todd, et al. "T Cell Activation Markers and African Mitochondrial DNA Haplogroups Among non-Hispanic Black Participants in AIDS Clinical Trials Group Study 384." PloS One, vol. 7, no. 8, 2012, pp. e43803.
Hulgan T, Robbins GK, Kalams SA, et al. T cell activation markers and African mitochondrial DNA haplogroups among non-Hispanic black participants in AIDS clinical trials group study 384. PLoS One. 2012;7(8):e43803.
Hulgan, T., Robbins, G. K., Kalams, S. A., Samuels, D. C., Grady, B., Shafer, R., Murdock, D. G., Selph, D., Haas, D. W., & Pollard, R. B. (2012). T cell activation markers and African mitochondrial DNA haplogroups among non-Hispanic black participants in AIDS clinical trials group study 384. PloS One, 7(8), e43803. https://doi.org/10.1371/journal.pone.0043803
Hulgan T, et al. T Cell Activation Markers and African Mitochondrial DNA Haplogroups Among non-Hispanic Black Participants in AIDS Clinical Trials Group Study 384. PLoS One. 2012;7(8):e43803. PubMed PMID: 22970105.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - T cell activation markers and African mitochondrial DNA haplogroups among non-Hispanic black participants in AIDS clinical trials group study 384. AU - Hulgan,Todd, AU - Robbins,Gregory K, AU - Kalams,Spyros A, AU - Samuels,David C, AU - Grady,Benjamin, AU - Shafer,Robert, AU - Murdock,Deborah G, AU - Selph,Doug, AU - Haas,David W, AU - Pollard,Richard B, AU - ,, Y1 - 2012/08/27/ PY - 2012/03/30/received PY - 2012/07/26/accepted PY - 2012/9/13/entrez PY - 2012/9/13/pubmed PY - 2013/1/23/medline SP - e43803 EP - e43803 JF - PloS one JO - PLoS One VL - 7 IS - 8 N2 - 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. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/22970105/T_cell_activation_markers_and_African_mitochondrial_DNA_haplogroups_among_non_Hispanic_black_participants_in_AIDS_clinical_trials_group_study_384_ L2 - https://dx.plos.org/10.1371/journal.pone.0043803 DB - PRIME DP - Unbound Medicine ER -