title: Natural history of human immunodeficiency virus disease in perinatally infected children: an analysis from the Pediatric Spectrum of Disease Project.
abstract: OBJECTIVE
  To describe the progression of human immunodeficiency virus (HIV) disease through clinical stages from birth to death among a large number of perinatally infected children.
  
  
  METHODS
  The Pediatric Spectrum of Disease (PSD) project, coordinated by the Centers for Disease Control and Prevention (CDC), has conducted active surveillance for HIV disease since 1988 in seven geographic regions. PSD data are collected from medical and social service records every 6 months through practitioners at each participating hospital clinic. We analyzed data from perinatally HIV-infected children born between 1982 and 1993. The natural history of HIV disease was divided into five progressive stages using the clinical categories in the CDC 1994 pediatric HIV classification system: stage N, no signs or symptoms; stage A, mild signs or symptoms; stage B, moderate signs or symptoms; stage C, severe signs or symptoms; and stage D, death. A five-stage Markov model was fitted to the PSD data. To compare the estimates from the PSD project with the published estimates, we also fitted an alternative Markov model using acquired immunodeficiency syndrome (AIDS; 1987 case definition) in place of stage C and also calculated standard Kaplan-Meier estimates.
  
  
  RESULTS
  A total of 2148 perinatally HIV-infected children were included in the analysis. The estimated mean times spent in each stage were: N, 10 months; A, 4 months; B, 65 months; and C, 34 months. We estimated that a child born with HIV infection has a 50% (95% confidence interval [CI], 40%-60%) chance of severe signs or symptoms developing by 5 years of age and a 75% (95% CI, 68%-82%) chance of surviving to 5 years of age. For a child in stage B, there is a 60% (95% CI, 49%-71%) chance of severe signs or symptoms developing within the next 5 years and a 65% (95% CI, 56%-73%) chance of surviving 5 more years. The estimated mean time from birth to stage C was 6.6 (95% CI, 5.7-7.5) years, and the estimated mean survival time from birth was 9.4 (95% CI, 8.1-10.7) years. From the alternative Markov model, the estimated mean time from birth to AIDS was 4.8 (95% CI, 4.5-5.2) years.
  
  
  CONCLUSIONS
  Markov modeling using the revised pediatric classification system allowed us to describe the natural history of HIV disease in children before diagnosis of AIDS. On average, children progress to moderate symptoms in the second year of life and then remain moderately symptomatic for more than half of their expected lives, underscoring their need for clinical care before the onset of AIDS. The results from the Markov model are useful in family counseling, health care planning, and clinical trial designs.
authors.affiliation: Department of Biostatistics, Rollins School of Public Health, Emory University, Atlanta, Georgia 30322, USA.
authors.forename: H X
authors.initials: HX
authors.lastname: Barnhart
authors.forename: M B
authors.initials: MB
authors.lastname: Caldwell
authors.forename: P
authors.initials: P
authors.lastname: Thomas
authors.forename: L
authors.initials: L
authors.lastname: Mascola
authors.forename: I
authors.initials: I
authors.lastname: Ortiz
authors.forename: H W
authors.initials: HW
authors.lastname: Hsu
authors.forename: J
authors.initials: J
authors.lastname: Schulte
authors.forename: R
authors.initials: R
authors.lastname: Parrott
authors.forename: Y
authors.initials: Y
authors.lastname: Maldonado
authors.forename: R
authors.initials: R
authors.lastname: Byers
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000145:classification / Q000151:congenital / Q000503:physiopathology; D002423:Cause of Death; D002487:Centers for Disease Control and Prevention, U.S.; D002648:Child; D002675:Child, Preschool; D002986:Clinical Trials as Topic; D016001:Confidence Intervals; D003376:Counseling; D018450:Disease Progression; D015658:HIV Infections / Q000145:classification / Q000151:congenital* / Q000503:physiopathology*; D006285:Health Planning; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D015233:Models, Statistical; D011159:Population Surveillance; D012107:Research Design; D015996:Survival Rate; D013997:Time Factors; D014481:United States