title: Incidence of World Health Organization stage 3 and 4 events, tuberculosis and mortality in untreated, HIV-infected children enrolling in care before 1 year of age: an IeDEA (International Epidemiologic Databases To Evaluate AIDS) East Africa regional analysis.
abstract: BACKGROUND
  Few studies have reported CD4%- and age-stratified rates of World Health Organization Stage 3 (WHO3) events, World Health Organization Stage 4 (WHO4) events, tuberculosis (TB) and mortality in HIV-infected infants before initiation of antiretroviral therapy.
  
  
  METHODS
  HIV-infected children enrolled before 1 year of age in the International Epidemiologic Databases to Evaluate AIDS East Africa region (October 1, 2002, to November, 2008) were included. We estimated incidence rates of earliest clinical event (WHO3, WHO4 and TB), before antiretroviral therapy initiation per local guidelines, stratified by current age (< or ≥6 months) and current CD4% (<15%, 15-24%, ≥25%). CD4%-stratified mortality rates were estimated separately for children who did not experience a clinical event ("background" mortality) and for children who experienced an event, including "acute" mortality (≤30 days post event) and "later" mortality (>30 days post event).
  
  
  RESULTS
  Among 847 children (median enrollment age: 4.8 months; median pre-antiretroviral therapy follow up: 10.8 months; 603 (71%) with ≥1 CD4% recorded), event rates were comparable for those aged <6 and ≥6 months. Current CD4% was associated with risk of WHO4 events for children <6 months of age and with all evaluated events for children ≥6 months old (P < 0.05). "Background" mortality was 3.7-8.4/100 person-years (PY). "Acute" mortality (≤30 days post event) was 33.8/100 PY (after TB) and 41.1/100 PY (after WHO3 or WHO4). "Later" mortality (>30 days post event) ranged by CD4% from 4.7 to 29.1/100 PY.
  
  
  CONCLUSIONS
  In treatment-naïve, HIV-infected infants, WHO3, WHO4 and TB events were common before and after 6 months of age and led to substantial increases in mortality. Early infant HIV diagnosis and treatment are critically important, regardless of CD4%.
authors.affiliation: From the *Division of Infectious Diseases and Medical Practice Evaluation Center; †Division of General Medicine and Medical Practice Evaluation Center, Massachusetts General Hospital, Boston, MA; ‡Department of Child Health and Paediatrics, Moi University School of Medicine, Eldoret, Kenya; §Department of Orthopedic Surgery, Brigham and Women's Hospital, Boston, MA; ¶Department of Biostatistics, Indiana University; ‖Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN; **ICAP, Mailman School of Public Health, Columbia University and College of Physicians and Surgeons, Columbia University, NY; ††Family AIDS Care and Education Service (FACES) program, Kisumu, Kenya; ‡‡Department of Pediatrics, University of California, San Francisco, CA; §§Masaka Regional Referral Hospital, AHF-Uganda Cares Masaka, Uganda; and ¶¶Division of Infectious Disease, Indiana University School of Medicine, Indianapolis, IN.
authors.forename: Andrea
authors.initials: A
authors.lastname: Ciaranello
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Lu
authors.forename: Samuel
authors.initials: S
authors.lastname: Ayaya
authors.forename: Elena
authors.initials: E
authors.lastname: Losina
authors.forename: Beverly
authors.initials: B
authors.lastname: Musick
authors.forename: Rachel
authors.initials: R
authors.lastname: Vreeman
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Freedberg
authors.forename: Elaine J
authors.initials: EJ
authors.lastname: Abrams
authors.forename: Lisa
authors.initials: L
authors.lastname: Dillabaugh
authors.forename: Katie
authors.initials: K
authors.lastname: Doherty
authors.forename: John
authors.initials: J
authors.lastname: Ssali
authors.forename: Constantin T
authors.initials: CT
authors.lastname: Yiannoutsos
authors.forename: Kara
authors.initials: K
authors.lastname: Wools-Kaloustian
mesh_terms: D017088:AIDS-Related Opportunistic Infections; D000351:Africa, Eastern / Q000453:epidemiology; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000453:epidemiology* / Q000382:microbiology* / Q000401:mortality; D006801:Humans; D015994:Incidence; D007223:Infant; D008297:Male; D014376:Tuberculosis / Q000453:epidemiology* / Q000401:mortality / Q000821:virology*; D014944:World Health Organization