CROI 2017 Abstract e-Book

Abstract eBook

Poster and Themed Discussion Abstracts

351 COGNITIVE TRAJECTORIES IN SUPPRESSED HIV INFECTION INDICATE EVOLVING DISEASE ACTIVITY Chloe Gott 1 , Thomas Gates 2 , Nadene Dermody 1 , Bruce Brew 3 , Lucette Cysique 4 1 Macquarie Univ, North Ryde, NSW, Australia, 2 St Vincent’s Hosp, Sydney, Darlinghurst, NSW, Australia, 3 Univ of New South Wales, Darlinghurst, NSW, Australia, 4 NeuroSci Rsr Australia, Randwick, NSW, Australia Background: While the cross-sectional profile of HIV-associated neurocognitive disorder (HAND) is well described, the longitudinal rate and profile of cognitive decline in persons with stable, treated and virally-suppressed HIV infection is far from established. The aims of the current study were to: 1) quantify incident neurocognitive decline in HIV+ persons relative to controls. 2) determine the profile of cognitive trajectories as a function of historical and baseline HAND status. 3) determine which HIV disease biomarkers contribute to cognitive decline. Methods: Ninety-six HIV+ (97% virally undetectable; median current cART duration=24 months; median HIV duration=19 years, mean age=56 years) and 44 demographically comparable HIV- participants underwent standard neuropsychological testing assessing 7 cognitive domains at baseline and 18-month follow-up. We defined clinically relevant cognitive trajectories based on historical and baseline HAND status and cognitive decline using norms for change corrected for practise effect. Cognitive decline was defined using a continuous global change score (GCS) and dichotomous definition of clinically meaningful cognitive decline (decline/stable; 95% confidence interval, 1-tailed around the HIV- group mean GCS). Results: Relative to HIV- controls (4.5%), 14% of HIV+ participants were defined as having declined (p=.11). However, the HIV+ group scored significantly lower on global change scores (GCS) (p=.03), and showed greater decline in processing speed (p=.02) and mental flexibility/inhibition (p=.02) compared to controls. Having HAND at baseline significantly predicted cognitive decline at follow up (p=.005). We determined seven clinically relevant cognitive trajectories which in order of prevalence were: 1) Always neurocognitively-normal (39%), 2) Baseline impairment, stable (35%), 3) Long-term impairment, stable (9%), 4) Baseline impairment, decline (7%), 5) History of HAND, fully recovered (3%), 6) Incident decline at 18 months (3%), 7) Consistent decline (3%). There was no relationship between cognitive decline (accounting for historical and baseline HAND) and traditional HIV disease biomarkers. Conclusion: Despite long-term viral suppression, we found mostly subclinical levels of decline in psychomotor speed and executive functioning - well-established markers of HAND progression. Moreover, 57% of our cohort were undergoing slow evolution of their disease, challenging the prevalent notion of neurocognitive stability in virally-suppressed HIV infection.

Poster and Themed Discussion Abstracts

352LB LONGITUDINAL ANALYSIS SHOWS NO EVIDENCE FOR ACCELERATED BRAIN AGEING IN TREATED HIV James H. Cole 1 , Matthan W. Caan 2 , Jonathan Underwood 1 , Rosan van Zoest 3 , Davide De Francesco 4 , Alan Winston 1 , Caroline Sabin 5 , David J. Sharp 1 , Peter Reiss 6 , for the CO- morBidity in Relation to AIDS (COBRA) Collaboration 1 Imperial College London, London, United Kingdom, 2 Academic Medical Center Amsterdam, Amsterdam, Netherlands, 3 Amsterdam Institute for Global Health and Development, Amsterdam, Netherlands, 4 UCL, London, United Kingdom, 5 University College London, London, United Kingdom, 6 Stichting HIV monitoring and Academical Medical Center Amsterdam, Amsterdam, Netherlands Background: A major concern for people living with HIV is the reportedly high prevalence of cognitive impairment, which may reflect an exacerbation of the effects of ageing on the brain. Using longitudinal neuroimaging and neuropsychological data from participants in the EU-funded COBRA collaboration, we determined whether successfully treated HIV infection is associated with accelerated age-related changes to brain structure and function. Methods: HIV+ve people with plasma HIV RNA <50 copies/ml on antiretroviral therapy for >1 year and demographically comparable HIV-ve controls were recruited at centres in Amsterdam and London. Participants were assessed at baseline and two years using multi-modal magnetic resonance imaging (T1-weighted, diffusion, resting-state fMRI, arterial spin labelling, spectroscopy), processed to generate global and regional summary metrics of brain structure and function. Neuropsychological assessments (reported as domain T-scores adjusted for age, sex, education) tested the cognitive domains of attention, executive function, language, memory, motor function and processing speed. Between- group comparisons of baseline values and change over time were assessed using linear and mixed-effects regression respectively, with models accounting for age, time between assessments and (for neuroimaging only) intracranial volume and scanner type. Results: At baseline, the 134 HIV+ve people (mean age 57.4 [SD=7.4] years, 6.7% female) had smaller grey matter volume, abnormal white matter microstructure and poorer cognitive function compared to 79 HIV-ve controls (58.8 [7.8] years, 7.6% female). Age-related declines in neuroimaging measures were observed in both groups, e.g., HIV+ve people lost 0.82% of brain volume per year, while HIV-ve controls lost 0.77%. Importantly, there were no group differences in the rates of brain volume loss or change in any neuroimaging measure (p>0.1, Table). Measure of cognitive function showed limited change. In fact global cognition T-score increased in both groups (HIV+ve 0.79, HIV-ve 0.45). There were no group differences in rates of change in cognition (p>0.1), with the exception of attention T-score, where the groups became more similar. Conclusion: While HIV+ve persons had abnormal measures of brain structure and function at baseline, we found no difference in the dynamics of these measures over time between HIV+ve and HIV-ve persons. Our findings suggest that there is no evidence for accelerated brain ageing in successfully treated HIV+ve people.

CROI 2017 138