title: HIV-associated neurocognitive disorders before and during the era of combination antiretroviral therapy: differences in rates, nature, and predictors.
abstract: Combination antiretroviral therapy (CART) has greatly reduced medical morbidity and mortality with HIV infection, but high rates of HIV-associated neurocognitive disorders (HAND) continue to be reported. Because large HIV-infected (HIV+) and uninfected (HIV-) groups have not been studied with similar methods in the pre-CART and CART eras, it is unclear whether CART has changed the prevalence, nature, and clinical correlates of HAND. We used comparable methods of subject screening and assessments to classify neurocognitive impairment (NCI) in large groups of HIV + and HIV - participants from the pre-CART era (1988-1995; N = 857) and CART era (2000-2007; N = 937). Impairment rate increased with successive disease stages (CDC stages A, B, and C) in both eras: 25%, 42%, and 52% in pre-CART era and 36%, 40%, and 45% in CART era. In the medically asymptomatic stage (CDC-A), NCI was significantly more common in the CART era. Low nadir CD4 predicted NCI in both eras, whereas degree of current immunosuppression, estimated duration of infection, and viral suppression in CSF (on treatment) were related to impairment only pre-CART. Pattern of NCI also differed: pre-CART had more impairment in motor skills, cognitive speed, and verbal fluency, whereas CART era involved more memory (learning) and executive function impairment. High rates of mild NCI persist at all stages of HIV infection, despite improved viral suppression and immune reconstitution with CART. The consistent association of NCI with nadir CD4 across eras suggests that earlier treatment to prevent severe immunosuppression may also help prevent HAND. Clinical trials targeting HAND prevention should specifically examine timing of ART initiation.
authors.affiliation: University of California, San Diego, CA, USA. rheaton@ucsd.edu
authors.forename: Robert K
authors.initials: RK
authors.lastname: Heaton
authors.forename: Donald R
authors.initials: DR
authors.lastname: Franklin
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Ellis
authors.forename: J Allen
authors.initials: JA
authors.lastname: McCutchan
authors.forename: Scott L
authors.initials: SL
authors.lastname: Letendre
authors.forename: Shannon
authors.initials: S
authors.lastname: Leblanc
authors.forename: Stephanie H
authors.initials: SH
authors.lastname: Corkran
authors.forename: Nichole A
authors.initials: NA
authors.lastname: Duarte
authors.forename: David B
authors.initials: DB
authors.lastname: Clifford
authors.forename: Steven P
authors.initials: SP
authors.lastname: Woods
authors.forename: Ann C
authors.initials: AC
authors.lastname: Collier
authors.forename: Christina M
authors.initials: CM
authors.lastname: Marra
authors.forename: Susan
authors.initials: S
authors.lastname: Morgello
authors.forename: Monica Rivera
authors.initials: MR
authors.lastname: Mindt
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Taylor
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Marcotte
authors.forename: J Hampton
authors.initials: JH
authors.lastname: Atkinson
authors.forename: Tanya
authors.initials: T
authors.lastname: Wolfson
authors.forename: Benjamin B
authors.initials: BB
authors.lastname: Gelman
authors.forename: Justin C
authors.initials: JC
authors.lastname: McArthur
authors.forename: David M
authors.initials: DM
authors.lastname: Simpson
authors.forename: Ian
authors.initials: I
authors.lastname: Abramson
authors.forename: Anthony
authors.initials: A
authors.lastname: Gamst
authors.forename: Christine
authors.initials: C
authors.lastname: Fennema-Notestine
authors.forename: Terry L
authors.initials: TL
authors.lastname: Jernigan
authors.forename: Joseph
authors.initials: J
authors.lastname: Wong
authors.forename: Igor
authors.initials: I
authors.lastname: Grant
mesh_terms: D015526:AIDS Dementia Complex / Q000150:complications / Q000188:drug therapy* / Q000453:epidemiology*; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D005260:Female; D006678:HIV / Q000472:pathogenicity*; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy* / Q000453:epidemiology*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D016896:Treatment Outcome; D055815:Young Adult