T Cell Activation Markers and African Mitochondrial DNA Haplogroups among Non-Hispanic Black Participants in AIDS Clinical Trials Group Study 384

Introduction

Mitochondrial function influences T cell dynamics and is affected bymitochondrial DNA (mtDNA) variation. We previously reported an associationbetween African mtDNA haplogroup L2 and less robust CD4 cell recovery onantiretroviral therapy (ART) in non-Hispanic black ACTG 384 subjects. Weexplored whether additional T cell parameters in this cohort differed bymtDNA haplogroup.

Methods

ACTG 384 randomized ART-naïve subjects to two different nucleosideregimens with efavirenz, nelfinavir, or both. CD4 and CD8 memory andactivation markers were available at baseline and week 48 on most subjects.mtDNA sequencing was performed on whole blood DNA, and haplogroups weredetermined. We studied non-Hispanic black subjects with HIV RNA <400copies/mL at week 48. Analyses included Wilcoxon ranksum test and linearregression.

Results

Data from 104 subjects were included. Major African mtDNA haplogroupsincluded L1 (N = 25), L2 (N = 31),and L3 (N = 32). Baseline age, HIV RNA, and CD4 cellsdid not differ between L2 and non-L2 haplogroups. Compared to non-L2haplogroups, L2 subjects had lower baseline activated CD4 cells (median12% vs. 17%; p = 0.03) and tended towardlower activated CD8 cells (41% vs. 47%;p = 0.06). At 48 weeks of ART, L2 subjects had smallerdecreases 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 baselineage, CD4 cells, HIV RNA, and naïve-to-memory CD4 cell ratio, haplogroupL2 was associated with lower baseline (p = 0.04) and48-week change in (p = 0.01) activated CD4 cells.

Conclusions

Among ART-naïve non-Hispanic blacks, mtDNA haplogroup L2 was associatedwith baseline and 48-week change in T cell activation, and poorer CD4 cellrecovery. These data suggest mtDNA variation may influence CD4 T celldynamics by modulating T cell activation. Further study is needed toreplicate these associations and identify mechanisms.