Changes in the incidence and predictors of human immunodeficiency virus–associated dementia in the era of highly active antiretroviral therapy

Objective Though effective anti–human immunodeficiency virus (HIV) therapies are now available, they have variable penetration into the brain. We therefore aimed to assess changes over calendar time in the risk for HIV‐associated dementia (HIV‐D), and factors associated with HIV‐D risk. Methods Using Concerted Action on Seroconversion to AIDS and Death in Europe (CASCADE) data, we analyzed factors associated with time from HIV seroconversion to HIV‐D using Cox models with time‐updated covariates. The effect of duration of infection was explored using flexible parametric survival models. Results 222 of 15,380 seroconverters developed HIV‐D. The incidence per 1,000 person‐years was 6.49 pre‐1997 (before highly active antiretroviral therapy was available), declining to 0.66 by 2003 to 2006. Compared with most recent CD4 count ≥ 350 cells/mm 3 , the adjusted relative risk (95% confidence interval) of HIV‐D was 3.47 (1.91–6.28), 10.19 (5.72–18.15), and 39.03 (22.96–66.36) at 200 to 349, 100 to 199, and 0 to 99 cells/mm 3 , respectively. In 2003 to 2006, older age at seroconversion (relative risk = 3.24 per 10‐year increase [95% confidence interval, 2.00–5.24]) and previous acquired immune deficiency syndrome diagnosis (relative risk = 4.92 [95% confidence interval, 1.43–16.92]) were associated with HIV‐D risk, independently of current CD4 count. HIV‐D risk appeared to increase during chronic infection, by 48% at 10 years after seroconversion compared with the lowest risk at 1.8 years. Interpretation HIV‐D incidence has reduced markedly since 1997. However, patients with low (<200 cells/mm 3 ) or even intermediate (200–349 cells/mm 3 ) CD4 counts, previous acquired immune deficiency syndrome diagnosis, longer HIV infection duration, and older age at seroconversion are at increased risk and should be closely monitored for neurocognitive disorders. Ann Neurol 2007