title: Adrenal enzyme impairment in neonates and adolescents treated with ritonavir and protease inhibitors for HIV exposure or infection.
abstract: BACKGROUND
  Human deficiency virus (HIV) protease inhibitors (PIs) are widely used drugs whose effects are pharmacologically enhanced by ritonavir, a potent cytochrome P450 inhibitor. We reported previously that prophylactic postnatal ritonavir-PI therapy in HIV-exposed neonates was associated with increases in plasma 17-hydroxyprogesterone (17-OHP) and dehydroepiandrosterone sulfate (DHEA-S).
  
  
  OBJECTIVE
  To further investigate adrenal function in neonates and adolescents given ritonavir-PI.
  
  
  METHODS
  Adrenal function was assessed prospectively in 3 HIV-exposed neonates given short-term prophylactic treatment and 3 HIV-infected adolescents given long-term treatment. Plasma cortisol, 17-OHP, 17-OH-pregnenolone, DHEA-S, and androstenedione were measured before and after ACTH administration.
  
  
  RESULTS
  None of the patients had clinical signs of adrenal dysfunction. The only neonate exposed to ritonavir-PI in utero had up to 3-fold increases in plasma 17-OHP. Increases in 17-OH-pregnenolone of up to 3.1-fold were noted in 4 of the 6 patients, and all 6 patients had elevations in DHEA-S (up to 20.4-fold increase) and/or DHEA (up to 4.7-fold) and/or androstenedione (up to 5.2-fold). All these parameters improved after treatment completion.
  
  
  CONCLUSIONS
  Neonates and adolescents given ritonavir-PI exhibit a similar adrenal dysfunction profile consistent with an impact on multiple adrenal enzymes. These abnormalities require evaluation, given the potentially long exposure times.
authors.affiliation: Pediatric Endocrinology Gynecology and Diabetology Unit, Assistance Publique-Hôpitaux de Paris (AP-HP) and IMAGINE Institute affiliate, Paris, France.
authors.forename: D
authors.initials: D
authors.lastname: Kariyawasam
authors.forename: A
authors.initials: A
authors.lastname: Simon
authors.forename: K
authors.initials: K
authors.lastname: Laborde
authors.forename: S
authors.initials: S
authors.lastname: Parat
authors.forename: P-F
authors.initials: PF
authors.lastname: Souchon
authors.forename: P
authors.initials: P
authors.lastname: Frange
authors.forename: S
authors.initials: S
authors.lastname: Blanche
authors.forename: M
authors.initials: M
authors.lastname: Polak
mesh_terms: D006907:17-alpha-Hydroxypregnenolone / Q000097:blood; D019326:17-alpha-Hydroxyprogesterone / Q000097:blood; D000293:Adolescent; D000311:Adrenal Glands / Q000187:drug effects* / Q000503:physiopathology; D019380:Anti-HIV Agents / Q000494:pharmacology* / Q000627:therapeutic use; D003687:Dehydroepiandrosterone / Q000097:blood; D019314:Dehydroepiandrosterone Sulfate / Q000097:blood; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007231:Infant, Newborn; D008297:Male; D011480:Protease Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D019438:Ritonavir / Q000494:pharmacology* / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D011480:Protease Inhibitors; D006907:17-alpha-Hydroxypregnenolone; D003687:Dehydroepiandrosterone; D019314:Dehydroepiandrosterone Sulfate; D019326:17-alpha-Hydroxyprogesterone; D019438:Ritonavir; D006854:Hydrocortisone