Mitochondrial genomics and CD4 T-cell count recovery after antiretroviral therapy initiation in AIDS clinical trials group study 384.

Grady BJ, Samuels DC, Robbins GK, Selph D, Canter JA, Pollard RB, Haas DW, Shafer R, Kalams SA, Murdock DG, Ritchie MD, Hulgan T, ACTG 384 and DACS 250 Study Teams
J Acquir Immune Defic Syndr. 2011 58 (4): 363-70

PMID: 21792066 · PMCID: PMC3204178 · DOI:10.1097/QAI.0b013e31822c688b

BACKGROUND - Mitochondrial DNA (mtDNA) variation has been associated with time to progression to AIDS and adverse effects from antiretroviral therapy (ART). In this study, full mitochondrial DNA (mtDNA) sequence data from US-based adult participants in the AIDS Clinical Trials Group study 384 was used to assess associations between mtDNA variants and CD4 T-cell recovery with ART.

METHODS - Full mtDNA sequence was determined using chip-based array sequencing. Sequence and CD4 cell count data was available at baseline and after ART initiation for 423 subjects with HIV RNA levels <400 copies per milliliter plasma. The primary outcome was change in CD4 count of ≥100 cells per cubic millimeter from baseline. Analyses were adjusted for baseline age, CD4 cell count, HIV RNA, and naive:memory CD4 cell ratio.

RESULTS - Race-stratified analysis of mtDNA variants with a minor allele frequency >1% revealed multiple mtDNA variants marginally associated (P < 0.05 before Bonferroni correction) with CD4 cell recovery. The most significant single nucleotide polymorphism associations were those tagging the African L2 haplogroup, which was associated with a decreased likelihood of ≥100 cells per cubic millimeter CD4 count increase at week 48 in non-Hispanic blacks (adjusted odds ratio = 0.17; 95% confidence interval = 0.06 to 0.53; P = 0.002).

CONCLUSIONS - An African mtDNA haplogroup was associated with CD4 cell recovery after ART in this clinical trial population. These initial findings warrant replication and further investigation to confirm the role of mtDNA variation in CD4 cell recovery during ART.

MeSH Terms (25)

Acquired Immunodeficiency Syndrome Adolescent Adult Aged Alkynes Anti-HIV Agents Base Sequence Benzoxazines CD4 Lymphocyte Count CD4-Positive T-Lymphocytes Cyclopropanes Drug Therapy, Combination Female Genome, Mitochondrial Haplotypes Humans Male Middle Aged Molecular Sequence Data Nelfinavir Polymorphism, Single Nucleotide RNA, Viral Treatment Outcome Viral Load Young Adult

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