title: Early severe HIV disease precedes early antiretroviral therapy in infants: Are we too late?
abstract: OBJECTIVE
  To describe the degree of HIV disease progression in infants initiating antiretroviral therapy (ART) by three months of age in a programmatic setting in South Africa.
  
  
  METHODS
  This was a programmatic cohort study.
  
  
  METHODS
  Electronic and manual data extraction from databases and antiretroviral registers in 20 public clinics in Cape Town and electronic data extraction from a large ART service at Chris Hani Baragwanath Hospital in Soweto were performed. Records of all infants initiated on ART by three months of age between June 2007 and September 2010 were extracted. Demographics, immunological and clinical stage at ART initiation were analyzed descriptively by chi-square, two-sample t-test and Kaplan-Meier methods.
  
  
  RESULTS
  A total of 403 records were identified: 88 in Cape Town and 315 in Soweto. Median age at ART initiation was 8.4 [interquartile range (IQR): 7.2-9.7] weeks. At ART initiation, 250 infants (62%) had advanced HIV disease (CD4% <25% or absolute CD4<1500 cells/mm(3) or WHO clinical Stage 3 or 4). Median age at ART initiation by site was 10.3 (IQR: 8.2-11.9) weeks in Cape Town and 8.6 (IQR: 7.7-10.0) weeks in Soweto infants (p<0.0001). In Cape Town, 73 infants (83%) had advanced HIV disease at ART initiation, compared to 177 infants (56%) in Soweto (p<0.0001). On logistic regression, each month increase in age at ART initiation lowered the odds of initiating ART in an optimal state (OR: 0.56, CI: 0.36-0.94) and increased the odds of advanced HIV disease at ART initiation (OR: 1.69, CI: 1.05-2.71).
  
  
  CONCLUSIONS
  ART initiation by three months of age may not adequately prevent disease progression. New emphasis on early diagnosis and rapid initiation of ART in the first weeks of life are essential to further reduce infant mortality.
authors.affiliation: Children's Infectious Diseases Clinical Research Unit (KID-CRU), Stellenbosch University and Tygerberg Children's Hospital, Cape Town, South Africa; innes@sun.ac.za.
authors.forename: Steve
authors.initials: S
authors.lastname: Innes
authors.affiliation: Perinatal HIV Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg and Chris Hani Baragwanath Hospital, Soweto, South Africa.
authors.forename: Erica
authors.initials: E
authors.lastname: Lazarus
authors.affiliation: Perinatal HIV Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg and Chris Hani Baragwanath Hospital, Soweto, South Africa.
authors.forename: Kennedy
authors.initials: K
authors.lastname: Otwombe
authors.affiliation: Perinatal HIV Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg and Chris Hani Baragwanath Hospital, Soweto, South Africa.
authors.forename: Afaaf
authors.initials: A
authors.lastname: Liberty
authors.affiliation: Perinatal HIV Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg and Chris Hani Baragwanath Hospital, Soweto, South Africa.
authors.forename: Ramona
authors.initials: R
authors.lastname: Germanus
authors.affiliation: Children's Infectious Diseases Clinical Research Unit (KID-CRU), Stellenbosch University and Tygerberg Children's Hospital, Cape Town, South Africa.
authors.forename: Anita Janse
authors.initials: AJ
authors.lastname: Van Rensburg
authors.affiliation: Anova Health Institute, Paarl, Western Cape, South Africa.
authors.forename: Nelis
authors.initials: N
authors.lastname: Grobbelaar
authors.affiliation: Anova Health Institute, Paarl, Western Cape, South Africa.
authors.forename: Theunis
authors.initials: T
authors.lastname: Hurter
authors.affiliation: Red Cross War Memorial Children's Hospital and the University of Cape Town, Cape Town, South Africa.
authors.forename: Brian
authors.initials: B
authors.lastname: Eley
authors.affiliation: Perinatal HIV Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg and Chris Hani Baragwanath Hospital, Soweto, South Africa.
authors.forename: Avy
authors.initials: A
authors.lastname: Violari
authors.affiliation: Children's Infectious Diseases Clinical Research Unit (KID-CRU), Stellenbosch University and Tygerberg Children's Hospital, Cape Town, South Africa.
authors.forename: Mark F
authors.initials: MF
authors.lastname: Cotton
mesh_terms: D000367:Age Factors; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count / Q000706:statistics & numerical data; D016009:Chi-Square Distribution; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology / Q000401:mortality; D006801:Humans; D007223:Infant; D053208:Kaplan-Meier Estimate; D016015:Logistic Models; D008297:Male; D013019:South Africa / Q000453:epidemiology
chemical_list: D019380:Anti-HIV Agents
keywords: South Africa; antiretroviral therapy; early infant diagnosis; infant HIV; programmatic cohort