Cancer Project Working Group for the Collaboration of Observational HIV Epidemiological Research Europe study in EuroCoord

 Kaposi sarcoma (KS) remains a frequent cancer in HIV-positive patients initiating combination antiretroviral therapy (cART). We examined incidence rates and risk factors for developing KS in different periods since starting cART in patients from European observational HIV-cohorts.  We included HIV-positive adults starting cART after 01/01/1996. We analyzed incidence rates and risk factors for developing KS up to 90, 180 days and one, two, five, and eight years after cART start and fitted univariable and multivariable Cox regression models.  We included 109,461 patients from 21 prospective clinical cohorts in Europe with 916 incident KS cases. The incidence rate per 100,000 person-years was highest six months after starting cART (953, 95% CI 866-1,048) and declined to 82 (95% CI 68-100) after five to eight years. Using multivariable analyses adjusted for exposure group, origin, age, type of first-line regimen and calendar year, low current CD4 cell counts increased the risk of developing KS throughout all observation periods after starting cART. Lack of viral control was not associated with the hazard of developing KS in the first year after cART initiation, but was over time since starting cART increasingly positively associated (p<0.001 for interaction).  In patients who started cART both incidence and risk factors for KS change with time since starting cART. Whereas early after starting cART low CD4 cell count is the dominant risk factor, detectable HIV-1 RNA viral load becomes an increasingly important risk factor in patients who started cART several years ago, independently of immunodeficiency.