title: Changes in the incidence and predictors of human immunodeficiency virus-associated dementia in the era of highly active antiretroviral therapy.
abstract: 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 > or = 350 cells/mm3, 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/mm3, 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.
  
  
  CONCLUSIONS
  HIV-D incidence has reduced markedly since 1997. However, patients with low (<200 cells/mm3) or even intermediate (200-349 cells/mm3) 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.
authors: Medical Research Council Clinical Trials Unit, London, United Kingdom.
authors: Krishnan
authors: K
authors: Bhaskaran
authors: Cristina
authors: C
authors: Mussini
authors: Andrea
authors: A
authors: Antinori
authors: Ann Sarah
authors: AS
authors: Walker
authors: Maria
authors: M
authors: Dorrucci
authors: Caroline
authors: C
authors: Sabin
authors: Andrew
authors: A
authors: Phillips
authors: Kholoud
authors: K
authors: Porter
mesh_terms: D015526:AIDS Dementia Complex / Q000188:drug therapy* / Q000453:epidemiology*; D000328:Adult; D000367:Age Factors; D017668:Age of Onset; D023241:Antiretroviral Therapy, Highly Active / Q000706:statistics & numerical data*; D018791:CD4 Lymphocyte Count / Q000639:trends; D018450:Disease Progression; D005060:Europe / Q000453:epidemiology; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000401:mortality*; D006679:HIV Seropositivity / Q000453:epidemiology; D018451:Homosexuality, Male; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D012307:Risk Factors; D012309:Risk-Taking; D012720:Severity of Illness Index; D012725:Sexual Behavior; D016019:Survival Analysis; D013997:Time Factors; D019562:Viral Load