title: Early antiretroviral treatment reduces risk of bacille Calmette-Guérin immune reconstitution adenitis.
abstract: METHODS
  Two centres in Soweto and Cape Town, South Africa.
  
  
  OBJECTIVE
  To assess the effects of timing of initiation of antiretroviral treatment (ART) and other factors on the risk of bacille Calmette-Guérin (BCG) related regional adenitis due to immune reconstitution inflammatory  syndrome (BCG-IRIS) in human immunodeficiency virus (HIV) infected infants.
  
  
  METHODS
  HIV-infected infants aged 6-12 weeks with CD4 count ≥25% enrolled in the Children with HIV Early Antiretroviral Therapy (CHER) Trial received early (before 12 weeks) or deferred (after immunological  or clinical progression) ART; infants with CD4 count <25% all received early ART. All received BCG vaccination after birth. Reactogenicity to BCG was assessed prospectively during routine study follow-up.
  
  
  RESULTS
  Of 369 infants, 32 (8.7%) developed BCG-IRIS within 6 months of starting  ART, 28 (88%) within 2 months after ART initiation. Of the 32 cases, 30 (93.8%) had HIV-1 RNA > 750 000 copies/ml at initiation. Incidence of BCG-IRIS was 10.9 and 54.3 per 100 person-years (py) among infants with CD4 count ≥25% at enrolment receiving early (at median age 7.4  weeks) vs. deferred (23.2 weeks) ART, respectively (HR 0.24, 95%CI 0.11-0.53, P < 0.001). Infants with CD4 count <25% receiving early ART had intermediate incidence (41.7/100 py). Low CD4 counts and high HIV-1 RNA at initiation were the strongest independent risk factors  for BCG-IRIS.
  
  
  CONCLUSIONS
  Early ART initiation before immunological and/or clinical progression substantially reduces the risk of BCG-IRIS regional adenitis.
authors.affiliation: Children's Infectious Diseases Clinical Research Unit, Department of Paediatrics & Child Health, Stellenbosch University and Tygerberg Children's Hospital, Cape Town, South Africa. hrabie@sun.ac.za
authors.forename: H
authors.initials: H
authors.lastname: Rabie
authors.forename: A
authors.initials: A
authors.lastname: Violari
authors.forename: T
authors.initials: T
authors.lastname: Duong
authors.forename: S A
authors.initials: SA
authors.lastname: Madhi
authors.forename: D
authors.initials: D
authors.lastname: Josipovic
authors.forename: S
authors.initials: S
authors.lastname: Innes
authors.forename: E
authors.initials: E
authors.lastname: Dobbels
authors.forename: E
authors.initials: E
authors.lastname: Lazarus
authors.forename: R
authors.initials: R
authors.lastname: Panchia
authors.forename: A G
authors.initials: AG
authors.lastname: Babiker
authors.forename: D M
authors.initials: DM
authors.lastname: Gibb
authors.forename: M F
authors.initials: MF
authors.lastname: Cotton
mesh_terms: D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001500:BCG Vaccine / Q000009:adverse effects* / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000235:genetics; D006801:Humans; D054019:Immune Reconstitution Inflammatory Syndrome / Q000139:chemically induced* / Q000517:prevention & control; D007223:Infant; D008199:Lymphadenitis / Q000139:chemically induced / Q000517:prevention & control; D008297:Male; D011446:Prospective Studies; D012367:RNA, Viral; D012307:Risk Factors; D013019:South Africa; D013997:Time Factors
chemical_list: D019380:Anti-HIV Agents; D001500:BCG Vaccine; D012367:RNA, Viral