CROI 2017 Abstract e-Book

Abstract eBook

Poster and Themed Discussion Abstracts

Poster and Themed Discussion Abstracts

389 CEREBROSPINAL FLUID CONCENTRATION OF THE SYNAPTIC MARKER NEUROGRANIN IN HIV Maria C. Brühl 1 , Aylin Yilmaz 2 , Lars Hagberg 2 , Dietmar Fuchs 3 , Kaj Blennow 1 , Henrik Zetterberg 2 , Richard W. Price 4 , Magnus Gisslén 2 1 Sahlgrenska Univ Hosp, Gothenburg, Sweden, 2 Sahlgrenska Academy at the Univ of Gothenburg, Gothenburg, Sweden, 3 Innsbruck Med Univ, Innsbruck, Austria, 4 San Francisco General Hosp, San Fransisco, CA, USA Background: HIV-associated dementia (HAD) that represents the most advanced stage of HIV-associated neurocognitive disorders (HAND) is characterized by evident neuronal damage and loss. The incidence of HAD has decreased substantially since the introduction of combination antiretroviral therapy (cART) but milder forms of HAND persist also in patients on otherwise effective cART. Several biomarkers in CSF have been shown to mirror the late neuronal damage and intrathecal immune activation in people living with HIV (PLHIV), in particular neurofilament light protein (NFL) and neopterin. We hypothesize that synapses are involved early in the neuropathogenic pathways. To test this hypothesis, we have analyzed the synaptic marker neurogranin (NG) in a cohort of PLHIV thoroughly classified by systemic disease progression, CNS symptomatology, and ART. Methods: A cross-sectional study using archived CSF samples from two academic centers: Sahlgrenska University Hospital, Gothenburg, Sweden and San Francisco General Hospital, CA, USA was performed. The study population consisted of 149 PLHIV divided into 6 subgroups in regard to neurological symptoms and CD4 counts and 16 HIV-negative controls. CSF NG, NFL, and neopterin concentrations were measured by ELISA. Results: There were no significant differences in CSF NG levels between the various subgroups, although there was a relatively wide range within each group (figure 1a). CSF NFL concentrations were highest in the HAD group. The results also showed a trend of increased concentrations in participants with lower CD4 counts, all in agreement with earlier studies (figure 1b). A significant correlation was found between CSF NG and CSF NFL concentrations (r = 0,38, p < 0,0001) (figure 1c). Conclusion: With an ageing population of PLHIV on cART it is essential to early identify neurological impairment and discriminate between HAND and other forms of cognitive disorders. CNS immune activation and axonal injury, the latter mirrored by increased CSF NFL levels, are common features in HIV CNS disorder but the HAND neuropathogenesis is still not completely understood. Our hypothesis of early synaptic injury could not be confirmed by increased CSF concentration of the synaptic marker neurogranin in our study population with CNS symptoms. This either indicate that synaptic injury does not precede axonal injury in HIV-associated CNS disease or that CSF neurogranin is not a sensitive enough biomarker for synaptic impairment in HAND, which would contrast its utility in AD.

390 THE HUMAN GUT MICROBIOME AND HIV-ASSOCIATED NEUROCOGNITIVE DISORDERS

Josue Perez-Santiago 1 , Sara Gianella 2 , Ajay Bharti 1 , Debralee Cooksonv 1 , Robert K. Heaton 2 , Igor Grant 2 , Scott Letendre 1 , Scott N. Peterson 3 1 Univ of California San Diego, San Diego, CA, USA, 2 Univ of California San Diego, La Jolla, CA, USA, 3 Sanford Burnham Prebys Med Discovery Inst, La Jolla, CA, USA Background: Although advances in antiretroviral therapy (ART) have dramatically improved longevity, up to half of HIV+ adults still develop HIV associated neurocognitive (NC) disorders (HAND), even after achieving viral suppression. The mechanisms leading to HAND remain unclear, limiting the development of effective interventions. The gut microbiome has been implicated in the development and function of brain circuits that support emotion and cognition. Here we investigated the association between the gut microbiome of subjects with or without HAND.

CROI 2017 157