title: Cognitive change trajectories in virally suppressed HIV-infected individuals indicate high prevalence of disease activity.
abstract: BACKGROUND
  The longitudinal rate and profile of cognitive decline in persons with stable, treated, and virally suppressed HIV infection is not established. To address this question, the current study quantifies the rate of cognitive decline in a cohort of virally suppressed HIV+ persons using clinically relevant definitions of decline, and determine cognitive trajectories taking into account historical and baseline HAND status.
  
  
  METHODS
  Ninety-six HIV+ (clinically stable and virally undetectable) and 44 demographically comparable HIV- participants underwent standard neuropsychological testing at baseline and 18-months follow-up. We described clinically relevant cognitive trajectories based on standard definitions of historical and baseline HAND status and cognitive decline. Historical, moderate to severe HAND was formally diagnosed at the start of the cART era in 15/96 participants based on clinical neurological and neuropsychological assessment. The same standard of care has been applied to all participants at St. Vincent's Hospital Infectious Disease Department for the duration of their HIV infection (median of 20 years).
  
  
  RESULTS
  Relative to HIV- controls (4.5%), 14% of HIV+ participants declined (p = .11), they also scored significantly lower on the global change score (p = .03), processing speed (p = .02), and mental flexibility/inhibition (p = .02) domains. Having HAND at baseline significantly predicted cognitive decline at follow up (p = .005). We determined seven clinically relevant cognitive trajectories taking into account whether participant has a history of HAND prior to study entry (yes/no); their results on the baseline assessment (baseline impairment: yes/no) and their results on the 18-month follow up (decline or stable) which in order of prevalence were: 1) No HAND history, no baseline impairment, 18-month follow-up stable (39%), 2) No HAND history, baseline impairment, 18-month follow-up stable (35%), 3) History of HAND; baseline impairment, 18-month follow-up stable (9%) 4) No history of HAND, baseline impairment, 18-month follow-up decline (7%), 5) History of HAND, no baseline impairment, 18-month follow-up stable (3%), 6) No HAND history, no baseline impairment, 18-month follow-up decline (3%) 7) History of HAND, baseline impairment, 18-month follow-up decline (3%). There was no relationship between cognitive decline (taking into account historical and baseline HAND) and traditional HIV disease biomarkers.
  
  
  CONCLUSIONS
  Despite long-term viral suppression, we found mostly subclinical levels of decline in psychomotor speed and executive functioning (mental flexibility and cognitive inhibition); well-established markers of HAND progression. Moreover, 57% of our cohort is undergoing slow evolution of their disease, challenging the notion of prevalent neurocognitive stability in virally suppressed HIV infection.
authors.affiliation: Psychology Department, Macquarie University, Sydney, NSW, Australia.|Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia.
authors.forename: Chloe
authors.initials: C
authors.lastname: Gott
authors.affiliation: Departments of HIV and Neurology St Vincent's Hospital and Peter Duncan Neurosciences Unit St Vincent's Centre for Applied Medical Research Centre, Darlinghurst, NSW, Australia.
authors.forename: Thomas
authors.initials: T
authors.lastname: Gates
authors.affiliation: Psychology Department, Macquarie University, Sydney, NSW, Australia.|Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia.
authors.forename: Nadene
authors.initials: N
authors.lastname: Dermody
authors.affiliation: Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia.|Departments of HIV and Neurology St Vincent's Hospital and Peter Duncan Neurosciences Unit St Vincent's Centre for Applied Medical Research Centre, Darlinghurst, NSW, Australia.
authors.forename: Bruce J
authors.initials: BJ
authors.lastname: Brew
authors.affiliation: Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia.|Departments of HIV and Neurology St Vincent's Hospital and Peter Duncan Neurosciences Unit St Vincent's Centre for Applied Medical Research Centre, Darlinghurst, NSW, Australia.|Neuroscience Research Australia (NeuRA), Sydney, NSW, Australia.
authors.forename: Lucette A
authors.identifier: http://orcid.org/0000-0002-7711-6373
authors.initials: LA
authors.lastname: Cysique
mesh_terms: D000704:Analysis of Variance; D015415:Biomarkers; D003071:Cognition; D060825:Cognitive Dysfunction; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000453:epidemiology* / Q000523:psychology*; D006801:Humans; D015994:Incidence; D008297:Male; D015995:Prevalence; D000072339:Sexual and Gender Minorities
chemical_list: D015415:Biomarkers