CROI 2017 Abstract e-Book

Abstract eBook

Poster and Themed Discussion Abstracts

340 CNS INFLAMMATION STILL PRESENT AFTER >10 YEARS OF EFFECTIVE ANTIRETROVIRAL THERAPY Gustaf O. Hammarlund 1 , Arvid Edén 1 , Åsa Mellgren 2 , Dietmar Fuchs 3 , Henrik Zetterberg 1 , Lars Hagberg 1 , Staffan Nilsson 4 , Aylin Yilmaz 1 , Magnus Gisslén 1 1 Univ of Gothenburg, Gothenburg, Sweden, 2 South Älvsborgs Hosp, Borås, Sweden, 3 Innsbruck Med Univ, Innsbruck, Austria, 4 Chalmers Univ of Tech, Gothenburg, Sweden Background: Despite long-term viral suppression by antiretroviral therapy (ART), low-grade intrathecal immune activation can be found in a substantial proportion of people living with HIV (PLHIV). However, the clinical significance of ongoing immune activation during virally suppressive ART remains unclear. The aim of this study was to examine residual intrathecal immune activation in relation to signs of neuronal injury and neurocognitive impairment in PLHIV virally suppressed on ART for more than 10 years. Methods: Neurologically asymptomatic PLHIV on ART ≥ 10 years with plasma HIV-RNA levels < 50 copies/mL for ≥ 9.5 years were retrospectively included. HIV-RNA, neopterin (a well characterized marker of microglial/macrophage activation) and neurofilament light protein (NFL), a sensitive marker of neuronal injury, were analyzed in paired plasma and cerebrospinal fluid (CSF) samples in 22 patients. Pre-treatment samples were available in 15 subjects. Cognitive function in five domains was assessed by CogState (a computerized cognitive testing system validated in PLHIV) at follow-up. The CogStateBrief Battery consists of four tests: detection (DET) measuring psychomotor function and attention, identification (ID) assessing speed of information processing and attention, one card learning (OCL) which is a learning test and one back (OB) test which assess working memory. Results: CSF neopterin decreased significantly from in median (IQR) 18.6 (10.9-28.8) to 5.95 (4.6-7.9) nmol/L after treatment initiation (p < 0.001). Twelve of twenty-two (55 %) participants still had CSF neopterin above the upper normal reference limit (5.8 nmol/L) despite > 10 years of ART. CSF NFL, that normally increase with ageing, also decreased during the treatment period from in median (IQR) 1030, (541-1220), to 480 (290-750) ng/L (p < 0.05). No significant correlations were found between CSF neopterin and CSF NFL or neurocognitive performance. No difference was seen in CSF NFL or neurocognitive performance in subjects with normal compared to increased CSF neopterin. Conclusion: ART significantly decreases intrathecal immune activation, but, despite effective treatment for > 10 years, 55% of PLHIV continue to show signs of macrophage/ microglia activation in the central nervous system. Importantly, no associations was found between elevated neopterin and neurocognitive performance or signs of neuronal injury. 341 MONOCYTE ACTIVATION IS ASSOCIATED WITH COGNITION IN SUPPRESSED HIV-INFECTED WOMEN Brandon M. Imp 1 , Leah H. Rubin 2 , Phyllis Tien 3 , Michael Plankey 4 , Elizabeth T. Golub 5 , Audrey French 6 , Victor Valcour 3 , for theWomen's Interagency HIV Study (WIHS) 1 Rutgers Robert Wood Johnson Med Sch, Piscataway, NJ, USA, 2 Univ of Illinois at Chicago, Chicago, IL, USA, 3 Univ of California San Francisco, San Francsico, CA, USA, 4 Georgetown Univ, Washington, DC, 5 The Johns Hopkins Univ, Baltimore, MD, USA, 6 Rush Univ, Chicago, IL, USA Background: Cognitive impairment in HIV-infected individuals persists despite viral suppression. Monocyte-related immune activation is a likely underlying mechanism. We measured immune activation and cognition in a cohort of HIV-infected and -uninfected women from the Women’s Interagency HIV Study (WIHS). Methods: Blood levels of inflammatory markers (soluble CD163 (sCD163), soluble CD14 (sCD14), CRP, and IL-6) and a gut microbial translocation marker (intestinal fatty acid binding protein (I-FABP)) were measured in 253 women (73% HIV-infected). All women completed a one-hour cognitive battery. Neuropsychological testing z-scores were created from internal HIV-negative controls to develop seven composite indices (verbal learning, verbal memory, attention/concentration, executive functioning, psychomotor speed, verbal fluency, and fine motor skills). Markers were compared to concurrent (+/- one semiannual visit) neuropsychological testing performance using multivariable linear regression models adjusted for enrollment site, HIV and HCV status, antidepressants, depressive symptoms, hypertension, income, and number of previous cognitive test exposures. Results: Participants averaged 47 years old, completed 12.9 years of education, and were mostly Black, non-Hispanic (67%). 74%were HIV-infected, where 54% had a CD4 count of >500 cells/mm3 and 50% had an undetectable viral load. Higher sCD163 levels were associated with worse overall performance and worse verbal learning, verbal memory, executive function, psychomotor speed, and fine motor skills (p’s<0.05). Higher sCD14 levels were associated with worse verbal learning, verbal memory, executive function, and psychomotor speed (p’s<0.05). For women with viral suppression, sCD163 remained associated with worse overall performance, verbal memory, psychomotor speed, and fine motor skills (p’s<0.05). sCD14 remained associated with worse executive function (p<0.05). CRP, IL-6, and I-FABP were not associated with worse cognitive performance. Conclusion: Monocyte activation markers were associated with worse cognitive performance, and these associations persisted among HIV-infected women with viral suppression. Persistent inflammatory mechanisms related to monocytes correlate to cognitive outcomes.

Poster and Themed Discussion Abstracts

CROI 2017 134