title: Timing of antiretroviral therapy initiation and its impact on disease progression in perinatal human immunodeficiency virus-1 infection.
abstract: OBJECTIVE
  Treatment with highly active antiretroviral therapy (HAART) reduces overall perinatal human immunodeficiency virus (HIV) type 1-related mortality. The effect of timing of HAART initiation on reduction of morbidity is not well defined. We evaluated the association of timing of HAART initiation on progression to moderate or severe disease.
  
  
  METHODS
  Retrospective, population-based study of 196 perinatally HIV-infected children followed from birth in northern California from 1988 to 2009.
  
  
  RESULTS
  Of 196 children, 58% received HAART and were followed for a median of 6.2 years after HAART initiation. HAART use was associated with improved survival to the age of 5 years: no HAART, 50% versus HAART, 88%; P < 0.0001. However, the advantage of initial HAART over mono or dual therapy transitioning to HAART was small and not statistically significant (P = 0.23). Starting HAART before the development of moderate or severe disease delayed the median age of diagnosis of moderate disease from 0.4 years (interquartile range, [0.3-0.8]) without HAART to 3.0 years ([interquartile range, 1.9-5.8]; P < 0.0001) with HAART. HAART initiation after progression to moderate or severe disease was associated with decreased progression to severe disease or death, respectively (moderate to severe: 8% [3/36] with HAART vs. 84% [70/83] with no HAART, P < 0.0001; severe to death: 9% [6/68] with HAART vs. 73% [49/67] with no HAART, P < 0.0001).
  
  
  CONCLUSIONS
  In perinatal HIV infection, HAART is associated with delayed progression and reduced mortality regardless of disease severity at HAART initiation. This finding reinforces US guidelines regarding HAART initiation at >1 year of age if children present with most clinical category B diagnoses, regardless of CD4 measurements or plasma HIV RNA level.
authors: Department of Medicine, Division of Infectious Diseases and Geographic Medicine, Stanford University, Stanford, CA, USA. Amy.Sturt@hhs.sccgov.org
authors: Amy S
authors: AS
authors: Sturt
authors: Meira S
authors: MS
authors: Halpern
authors: Barbara
authors: B
authors: Sullivan
authors: Yvonne A
authors: YA
authors: Maldonado
mesh_terms: D000293:Adolescent; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D002140:California; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D018450:Disease Progression; D004334:Drug Administration Schedule; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000401:mortality* / Q000503:physiopathology / Q000821:virology; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical; D008297:Male; D012720:Severity of Illness Index; D016019:Survival Analysis; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents