Epidemic Kaposi sarcoma (KS) is caused by human herpesvirus 8 (HHV-8) infection and HIV-induced immunosuppression. HHV-8 prevalence and access to HIV care vary between regions. HHV-8 prevalence is higher in Eastern Africa than Southern Africa, and lower in Europe and Asia. We compared the KS burden in HIV-positive children on combination antiretroviral therapy (ART) between Asia, Europe, Eastern and Southern Africa.
We analyzed cohort data of the International Epidemiologic Databases to Evaluate AIDS Southern Africa (IeDEA-SA), the Collaboration of Observational HIV Epidemiological Research in Europe (COHERE) in EuroCoord, and the TREAT Asia Pediatric HIV Observational Database (TApHOD). We included HIV-positive children aged <16 years who started ART between 1996 and 2014. We calculated KS incidence rates per 100,000 person-years (pys) and hazard ratios (HR) from Cox regression adjusted for region, sex, age at ART start, ART regimen, and ART start year. We used CD4 cell counts and CD4% to define degree of immunodeficiency at ART start according to WHO criteria.
We included 24,383 children from Asia (Cambodia, India, Indonesia, Malaysia, Vietnam, Thailand), Europe (Denmark, France, Germany, Spain, Netherlands, UK), Eastern Africa (Zambia, Zimbabwe) and Southern Africa (South Africa). Median age at ART start was 5.1 years and lower in Southern Africa than in the other regions, see Table. Most children (55%) started ART with advanced or severe immunodeficiency; 10% of children were in CDC stage C. We observed 25 incident KS cases on ART (68% boys; median age at KS diagnosis 10.0 years). KS incidence rates were 85/100,000 pys (95% confidence interval [CI] 55-132) in Eastern Africa, 26/100,000 pys (95% CI 9-82) in Europe, and 9/100,000 pys (95% CI 2-37) in Southern Africa. All KS cases in Europe were in children who originated in sub-Saharan Africa (KS incidence rate 82/100,000 pys). We observed no incident KS in Asia. KS risk increased with age (10-15 versus 0-4 years; adjusted HR 4.1; 95% CI 1.4-12.1) and with advanced stage of HIV/AIDS (CDC stage C versus A/B; adjusted HR 3.1; 95% CI 1.1-8.7) at ART start.
KS risk is substantial in HIV-positive children of sub-Saharan African origin, whether they live in Africa or Europe. In the absence of measures to prevent HHV-8 infection, ART should be initiated in a timely fashion, before advanced HIV/AIDS stage is reached, to reduce KS risk in these children.