CROI 2015 Program and Abstracts

Abstract Listing

Poster Abstracts

the individual miRNAs was more robust than that of CD4 nadir CD4 T cell levels. Bioinformatics analyses showed that these miRNAs were predicted to target genes involved in brain development, transcription, apoptosis of neural cells, and innate immune signaling. Conclusions: Our findings revealed differential expression of three cell plasma-derived miRNAs in HAND versus nonHAND patients. These results suggest that plasma miRNAs might be used as biomarkers for HAND and also provide insights into the underlying disease mechanisms. 472 Performance of 4 Tools to Screen for HIV-Associated Cognitive Impairment Judith Schouten 2 ;Tanja Su 2 ; Rosan A. van Zoest 1 ; FerdinandW.Wit 1 ; Ineke G. Stolte 5 ; AlanWinston 3 ; Peter Reiss 1 ; Peter Portegies 4 ; Gert J. Geurtsen 2 ; Ben A. Schmand 2 1 Amsterdam Institute for Global Health and Development, Amsterdam, Netherlands; 2 Academic Medical Center University of Amsterdam, Amsterdam, Netherlands; 3 Imperial College London, London, Netherlands; 4 Onze Lieve Vrouwe Gasthuis, Amsterdam, Netherlands; 5 Public Health Service of Amsterdam, Amsterdam, Netherlands Background: A high prevalence of mild cognitive impairment (CI) has been reported in HIV-infected individuals on combination antiretroviral therapy (cART). An accurate screening tool would be useful to identify those at risk of HIV-associated CI who should undergo neuropsychological assessment (NPA). We assessed diagnostic characteristics of four often advocated screening tools: Mini Mental State Examination (MMSE), HIV Dementia Scale (HDS), Montreal Cognitive Assessment (MoCA), and a 3-item questionnaire published by Simioni et al (Simioni questionnaire). Methods: Each screening tool and NPA were applied to a subset of HIV-uninfected and HIV-infected men on cART and with undetectable viremia ≥ 12 months participating in the AGE h IV Cohort Study and enrolled in a nested cognitive substudy. Two methods were used to diagnose HIV-associated CI based on NPA outcomes: Frascati criteria as published by Antinori et al, and Multivariate Normative Comparison (MNC, comparing the cognitive profile of each HIV-infected individual with the overall cognitive profile of all HIV-negatives). Abnormal screening scores were defined by the following classical thresholds: MMSE ≤ 24/30, MoCA ≤ 25/30, HDS ≤ 10/16, HDS ≤ 14/16 and Simioni questionnaire ≥ 1/3 “yes, definitely”. Diagnostic characteristics and receiver operating characteristic (ROC) analyses of screening tools were assessed using Frascati and MNC as the gold standards. Optimal thresholds were identified by calculating Youden index. Results: HIV-positive and HIV-negative groups were highly comparable regarding age (median age: 54 years), sexual preference (92%MSM), educational level, subjective cognitive complaints, and depressive symptoms. HIV-infected men were infected for a median of 13.5 years and had undetectable viremia for a median of 8.3 years. Median nadir and current CD4-count were 170 and 625 cells/mm 3 . None of the screening tools showed statistically significant between-group differences; sensitivity and specificity were moderate at best (see table). The ROC area under the curve of MMSE, HDS, and MoCA was 0.63, 0.61 and 0.71, and 0.70, 0.67 and 0.58 using Frascati and MNC as gold standard respectively. No large improvements in sensitivity or specificity were seen using optimal thresholds (see table).

Poster Abstracts

Conclusions: Each of the four screening instruments performed poorly in detecting HIV-associated CI. Cognitive deficits in well-suppressed HIV infection are subtle, and no screening instrument so far seems optimal for use in clinical practice.

THURSDAY, FEBRUARY 26, 2015 Session P-G6 Poster Session

Poster Hall

2:30 pm– 4:00 pm Inflammation and Markers of Brain Injury in HAND 473 Astrocyte and Microglial Activation in Acute and Chronic HIV Pre- and Post-cART Michael Peluso 1 ;Victor G.Valcour 2 ; Jintanat Ananworanich 3 ; James L. Fletcher 4 ; SompornTipsuk 4 ; Bonnie Slike 3 ; Nittaya Phanuphak 4 ; Magnus Gisslén 5 ; Henrik Zetterberg 5 ; Serena Spudich 6 RV254/SEARCH 010 & SEARCH 011 StudyTeams 1 Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, US; 2 University of California San Francisco, San Francisco, CA, US; 3 Walter Reed Army Institute of Research, Bethesda, MD, US; 4 Thai Red Cross AIDS Research Centre, Bangkok, Thailand; 5 University of Gothenburg, Gothenburg, Sweden; 6 Yale University, New Haven, CT, US Background: Cerebrospinal fluid (CSF) YKL-40, a putative marker of astrocyte and microglial activation associated with Alzheimer’s disease and multiple sclerosis, is a potentially useful biomarker of processes occurring within the central nervous system (CNS) of HIV-infected individuals. To explore the impact of early HIV infection and early versus later initiation of combination antiretroviral therapy (cART) on the CNS, we measured CSF YKL-40 in subjects with acute HIV infection (AHI) before and after initiation of cART and compared the results with individuals initiating cART during chronic HIV infection (CHI) and HIV-uninfected Thai controls. Methods: AHI (n=33), CHI (n=34) and control (n=18) Thai subjects naïve to cART underwent blood and CSF sampling, followed by immediate cART initiation. CHI subjects met Thai criteria for initiating cART at baseline, having advanced disease typically with CD4 count <300. CSF was sampled at 24 (n=25) and 96 weeks (n=14) in the AHI and at 48 weeks

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CROI 2015