title: Incidence of AIDS-defining and Other Cancers in HIV-positive Children in South Africa: Record Linkage Study.
abstract: Little is known on the risk of cancer in HIV-positive children in sub-Saharan Africa. We examined incidence and risk factors of AIDS-defining and other cancers in pediatric antiretroviral therapy (ART) programs in South Africa.
  
  
  
  We linked the records of 5 ART programs in Johannesburg and Cape Town to those of pediatric oncology units, based on name and surname, date of birth, folder and civil identification numbers. We calculated incidence rates and obtained hazard ratios (HR) with 95% confidence intervals (CI) from Cox regression models including ART, sex, age and degree of immunodeficiency. Missing CD4 counts and CD4% were multiply imputed. Immunodeficiency was defined according to World Health Organization 2005 criteria.
  
  
  
  Data of 11,707 HIV-positive children were included in the analysis. During 29,348 person-years of follow-up 24 cancers were diagnosed, for an incidence rate of 82 per 100,000 person-years (95% CI: 55-122). The most frequent cancers were Kaposi sarcoma (34 per 100,000 person-years) and non-Hodgkin Lymphoma (31 per 100,000 person-years). The incidence of non AIDS-defining malignancies was 17 per 100,000. The risk of developing cancer was lower on ART (HR: 0.29; 95% CI: 0.09-0.86), and increased with age at enrollment (>10 vs. <3 years: HR: 7.3; 95% CI: 2.2-24.6) and immunodeficiency at enrollment (advanced/severe versus no/mild: HR: 3.5; 95% CI: 1.1-12.0). The HR for the effect of ART from complete case analysis was similar but ceased to be statistically significant (P = 0.078).
  
  
  
  Early HIV diagnosis and linkage to care, with start of ART before advanced immunodeficiency develops, may substantially reduce the burden of cancer in HIV-positive children in South Africa and elsewhere.
authors.affiliation: From the *Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland; †School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa; ‡Department of Paediatrics and Child Health, Chris Hani Baragwanath Academic Hospital, South Africa; §Harriet Shezi Children's Clinic, University of the Witwatersrand, Wits Reproductive Health and HIV Institute, Johannesburg, South Africa; ¶Department of Paediatrics and Child Health, Charlotte Maxeke Johannesburg Academic Hospital, University of the Witwatersrand, Johannesburg, South Africa; ‖Paediatric Infectious Diseases Unit, Red Cross War Memorial Children's Hospital; **Department of Paediatrics and Child Health, University of Cape Town, Cape Town, South Africa; ††Division of Infectious Diseases, Department of Medicine, University of Stellenbosch and Tygerberg Academic Hospital, Cape Town, South Africa; ‡‡Department of Paediatrics and Child Health, Tygerberg Hospital and Stellenbosch University, Tygerberg, Cape Town, South Africa; §§Khayelitsha ART Program, Médecins Sans Frontières, Cape Town, South Africa; ¶¶Empilweni Services and Research Unit, Rahima Moosa Mother and Child Hospital, University of the Witwatersrand, Johannesburg, South Africa; ‖‖Health Economics and Epidemiology Research Office, Department of Internal Medicine, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; ***Department of Paediatrics and Child Health, Red Cross War Memorial Children's Hospital and the University of Cape Town; and †††South African Medical Research Council, Cape Town, South Africa.
authors.forename: Julia
authors.initials: J
authors.lastname: Bohlius
authors.forename: Nicola
authors.initials: N
authors.lastname: Maxwell
authors.forename: Adrian
authors.initials: A
authors.lastname: Spoerri
authors.forename: Rosalind
authors.initials: R
authors.lastname: Wainwright
authors.forename: Shobna
authors.initials: S
authors.lastname: Sawry
authors.forename: Janet
authors.initials: J
authors.lastname: Poole
authors.forename: Brian
authors.initials: B
authors.lastname: Eley
authors.forename: Hans
authors.initials: H
authors.lastname: Prozesky
authors.forename: Helena
authors.initials: H
authors.lastname: Rabie
authors.forename: Daniela
authors.initials: D
authors.lastname: Garone
authors.forename: Karl-Günter
authors.initials: KG
authors.lastname: Technau
authors.forename: Mhairi
authors.initials: M
authors.lastname: Maskew
authors.forename: Mary-Ann
authors.initials: MA
authors.lastname: Davies
authors.forename: Alan
authors.initials: A
authors.lastname: Davidson
authors.forename: D Cristina
authors.initials: DC
authors.lastname: Stefan
authors.forename: Matthias
authors.initials: M
authors.lastname: Egger
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000150:complications*; D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D006801:Humans; D015994:Incidence; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009369:Neoplasms / Q000453:epidemiology*; D012307:Risk Factors; D013019:South Africa / Q000453:epidemiology