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 > 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.
Bhaskaran
Krishnan
K
Medical Research Council Clinical Trials Unit, London, United Kingdom.
Mussini
Cristina
C
Antinori
Andrea
A
Walker
Ann Sarah
AS
Dorrucci
Maria
M
Sabin
Caroline
C
Phillips
Andrew
A
Porter
Kholoud
K
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