CROI 2017 Abstract e-Book

Abstract eBook

Poster and Themed Discussion Abstracts

398 BRAIN HIV LATENCY LEADS TO A COMPLEX PATTERN OF NEUROCHEMICAL DYSREGULATION Lucette Cysique 1 , Michael V. Tobia 2 , Thomas Gates 3 , Lauriane Juge 2 , Simon Jones 4 , Caroline Rae 2 , Bruce Brew 4

1 NeuroSci Rsr Australia, Randwick, Australia, 2 Univ of New South Wales, Randwick, Australia, 3 St. Vincent’s Hosp, Sydney, Australia, 4 Univ of New South Wales, Darlinghurst, Australia Background: HIV brain latency may induce neuropathological events in virally suppressed HIV+ persons and persisting HIV-associated neurocognitive disorder (HAND). In the current study, we investigate whether major brain metabolites are impacted by a putative marker of brain HIV latency (CSF BCL11b, a microglia cell transcription factor that inhibits HIV transcription) in conjunction with CSF neopterin, CSF NFL, and CSF tat. Methods: Sample’s characteristics are presented in Table 1. All participants undertook a CSF lumbar puncture at baseline only; a 1H Magnetic Resonance Spectroscopy (MRS) scan, and a neuropsychological testing at both baseline and 18-months later. CSF samples were analyzed for BCL11b, neopterin, NFL, and tat using standard assays. 1H MRS included measurements of N-acetyl Aspartate (NAA), choline (Cho), Creatine (Cr), Myo-inositol (MI), glutamine/glutamate (Glx) in the frontal white matter (FWM), posterior cingulate cortex (PCC), and caudate nucleus area (CA). MRS spectra were measured with reference to the unsuppressed water signal and quantified using JMRUI V.03. Baseline cognitive impairment was based on the Frascati criteria, and cognitive decline was corrected for practice effect. Results: Baseline adjusted regression models for neopterin, NFL and tat showed that a higher CSF BCL11b was consistently associated with lower FWM Cr (when adjusted for neopterin: Std beta=-.30; p=.15; when adjusted for NFL: Std beta=-.51; p=.03; and when adjusted for tat: Std beta=-.47; p=.02). These analyses also revealed that FWM Cho was lower as a function of tat detectability (Std beta=-.51; p=.03). In longitudinal analyses, CSF neopterin was predictive of increased FWM Glx at follow-up, but not at baseline (Std Beta=-.33; p=.02). No CSF biomarkers was associated with baseline HAND, but NFL was associated with history of HAND (p=.02). Finally, a higher level of baseline NFL was predictive of cognitive decline (r=-.53; p=.005). Conclusion: Frontal white matter reduced cellular energy (Creatine decrease), in addition to disruption of cells’ membrane homeostasis (Choline decrease) may indicate HIV brain latency-related neuropathogenesis. Over-time, these dysregulations may lead to Glutamate excitotoxicity (Glx increase), and axonal injury (NFL increase). The latter appears to uniquely predict neurocognitive decline. These pilot data need to be further tested in a larger sample.

Poster and Themed Discussion Abstracts

399 CEREBRAL ENDOTHELIAL FUNCTION CORRELATES WITH PERFORMANCE ON COGNITIVE SCREENING TEST Natasha Mehta 1 , Yanling Li 2 , Yinghuan Hu 2 , Huanling Wang 2 , Weihai Xu 2 , Taisheng Li 2 , Felicia C Chow 1 1 Univ of California San Francisco, San Francisco, CA, USA, 2 Peking Union Med Coll Hosp, Beijing, China

Background: HIV-associated cognitive impairment remains prevalent in people living with HIV infection (PLWH) despite widespread use of combination antiretroviral therapy (ART). Increasing attention has been paid to the role of comorbid vascular disease and cerebrovascular injury in the development of HIV-associated cognitive impairment. We hypothesize that cerebral endothelial dysfunction, a marker of cerebrovascular risk, may be associated with cognitive impairment in PLWH. Methods: We recruited HIV-infected adults followed in the Peking Union Medical College Hospital HIV clinic in Beijing, China. All participants were on combination ART with undetectable plasma HIV RNA level. We used cerebral vasoreactivity (VR), defined as the percentage change in middle cerebral artery mean flow velocity on transcranial Doppler ultrasound (TCD) in response to breath holding, as the primary measure of cerebral endothelial function. Lower cerebral VR is indicative of worse cerebral endothelial function. Cognitive evaluation was performed on the same day as the TCD using the Montreal Cognitive Assessment (MoCA, Chinese Beijing version), a cognitive screening test commonly used in the clinical setting. We constructed linear regression models to estimate the association between cerebral VR and cognitive function. Results: Of 46 participants, the mean age was 42 years, and 15%were women. Thirty-three percent (33%) had a high school education or less. Mean cerebral VR was 1.07 [standard deviation (SD), 0.33], and mean MoCA score was 26.5 (SD 4.2). In models adjusted for education level, older age, female sex, and lower cerebral VR were associated with a lower MoCA score. In a multivariable model adjusted for age, sex and education level, we observed a trend toward a 1-point increase in the MoCA score for every 1 SD increase in mean cerebral VR (p=0.066). We did not find a statistically significant association between either traditional vascular risk factors (e.g., hypertension, smoking) or HIV-related variables (e.g., current or nadir CD4, ART class, duration of ART use) and the MoCA score. Conclusion: Among treated, virally suppressed PLWH, cerebral endothelial function correlated with cognitive performance on the MoCA, independent of age, sex and education level. Further evaluation of TCD-assessed cerebral VR as a potential preclinical marker of cognitive impairment and of cognitive decline in longitudinal studies is warranted. 400 RANDOMIZED TRIAL OF BRAIN FUNCTION CHANGE AFTER STARTING TDF/FTC+ATV/R OR ABC/3TC+EFV Ignacio Pérez-Valero 1 , Alicia Gonzalez-Baeza 1 , Lucia Bailon 1 , Belén Alejos 2 , Rocio Montejano 1 , Victor Hontanon 1 , Helena Melero 3 , Marisa Montes 1 , Carmen Bayon 1 , Jose R. Arribas 1

CROI 2017 162