Possible mitochondrial dysfunction and its association with antiretroviral therapy use in children perinatally infected with HIV.
BACKGROUND
Mitochondrial dysfunction has been associated with both human immunodeficiency virus (HIV) infection and exposure to antiretroviral therapy. Mitochondrial dysfunction has not been widely studied in HIV-infected children. We estimated the incidence of clinically defined mitochondrial dysfunction among children with perinatal HIV infection.


METHODS
Children with perinatal HIV infection enrolled in a prospective cohort study (Pediatric AIDS Clinical Trials Group protocols 219 and 219C) from 1993 through 2004 were included. Two clinical case definitions of mitochondrial dysfunction, the Enquête Périnatale Française criteria and the Mitochondrial Disease Classification criteria, were used to classify signs and symptoms that were consistent with possible mitochondrial dysfunction. Adjusted odds ratios of the associations between single and dual nucleoside reverse-transcriptase inhibitor use and possible mitochondrial dysfunction were estimated using logistic regression.


RESULTS
Overall, 982 (33.5%) of 2931 children met 1 or both case definitions of possible mitochondrial dysfunction. Mortality was highest among the 96 children who met both case definitions (20%). After adjusting for confounders, there was a higher risk of possible mitochondrial dysfunction among children who received stavudine regardless of exposure to other medications (odds ratio, 3.44 [95% confidence interval, 1.91-6.20]) or who received stavudine-didanosine combination therapy (odds ratio, 2.23 [95% confidence interval, 1.19-4.21]). Exposure to lamivudine and to lamivudine-stavudine were also associated with an increased risk of mitochondrial dysfunction.


CONCLUSIONS
Receipt of nucleoside reverse-transcriptase inhibitors, especially stavudine and lamivudine, was associated with possible mitochondrial dysfunction in children with perinatal HIV infection. Further studies are warranted to elucidate potential mechanisms of nucleoside reverse-transcriptase inhibitor toxicities.
University of Alabama School of Medicine, Birmingham, AL 35233, USA. mcrain@peds.uab.edu
Marilyn J
MJ
Crain
Miriam C
MC
Chernoff
James M
JM
Oleske
Susan B
SB
Brogly
Kathleen M
KM
Malee
Peggy R
PR
Borum
William A
WA
Meyer
Wendy G
WG
Mitchell
John H
JH
Moye
Heather M
HM
Ford-Chatterton
Russell B
RB
Van Dyke
George R
GR
Seage Iii
D000293:Adolescent; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy / Q000401:mortality / Q000503:physiopathology*; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D028361:Mitochondrial Diseases / Q000150:complications / Q000453:epidemiology / Q000503:physiopathology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000453:epidemiology; D011446:Prospective Studies; D012044:Regression Analysis; D018119:Stavudine / Q000627:therapeutic use; D014481:United States; D015215:Zidovudine / Q000627:therapeutic use
D019380:Anti-HIV Agents; D015215:Zidovudine; D018119:Stavudine