title: Mitochondrial genomics and CD4 T-cell count recovery after antiretroviral therapy initiation in AIDS clinical trials group study 384.
abstract: 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.
authors.affiliation: Vanderbilt University Center for Human Genetics Research, Nashville, TN, USA.
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Grady
authors.forename: David C
authors.initials: DC
authors.lastname: Samuels
authors.forename: Gregory K
authors.initials: GK
authors.lastname: Robbins
authors.forename: Doug
authors.initials: D
authors.lastname: Selph
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Canter
authors.forename: Richard B
authors.initials: RB
authors.lastname: Pollard
authors.forename: David W
authors.initials: DW
authors.lastname: Haas
authors.forename: Robert
authors.initials: R
authors.lastname: Shafer
authors.forename: Spyros A
authors.initials: SA
authors.lastname: Kalams
authors.forename: Deborah G
authors.initials: DG
authors.lastname: Murdock
authors.forename: Marylyn D
authors.initials: MD
authors.lastname: Ritchie
authors.forename: Todd
authors.initials: T
authors.lastname: Hulgan
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000480:Alkynes; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D001483:Base Sequence; D048588:Benzoxazines / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000821:virology; D003521:Cyclopropanes; D004359:Drug Therapy, Combination; D005260:Female; D054629:Genome, Mitochondrial; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D019888:Nelfinavir / Q000627:therapeutic use; D020641:Polymorphism, Single Nucleotide; D012367:RNA, Viral / Q000097:blood; D016896:Treatment Outcome; D019562:Viral Load / Q000187:drug effects; D055815:Young Adult
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D012367:RNA, Viral; D019888:Nelfinavir; C098320:efavirenz