CROI 2017 Abstract e-Book

Abstract eBook

Poster and Themed Discussion Abstracts

367 SEX-BASED DIFFERENCES IN HIV RESERVOIRS IN BRAIN AND NEUROCOGNITION Michelli Faria de Oliveira 1 , Masato Nakazawa 1 , Andrej Vitomirov 1 , Mitchell Zhao 1 , Ben Gouaux 2 , David Moore 2 , Ronald J. Ellis 2 , Davey M. Smith 1 , Sara Gianella 1 1 Univ of California San Diego, La Jolla, CA, USA, 2 Univ of California San Diego, San Diego, CA, USA Background: While antiretroviral therapy (ART) can reduce HIV RNA below the limit of detection in plasma, HIV DNA reservoirs can persist in anatomic compartments, as the central nervous system. The clinical and biological factors that influence HIV reservoirs in the brain are unknown. Methods: Paired autopsy tissues from frontal cortex [FC, N=61], occipital cortex [OCC, N=53], basal ganglia [BG, N=30]) and peripheral lymph tissue (LT, N=37) were collected from 63 HIV+ adults as part of the National NeuroAIDS Tissue Consortium between 1999-2014. All participants died with documented virologic suppression on ART (<50 or 400 copies/ml, assay-dependent) without evidence of major neurologic conditions. Genomic DNA was extracted by magnetic beads; levels of HIV DNA were measured by ddPCR and normalized by RPP30. Neurocognitive (NC) functioning was assessed at the last visit (median 3 months before death) and participants were categorized as: (1) no NC impairment (NCI) (2) subclinical NCI, (3) mild NCI (4) severe NCI (all HIV-associated), (5) non-HIV associated NCI. Bayesian hierarchical regression model was used to evaluate the relationship between brain regions, sex, and NC functioning after adjusting for significant covariates. Significance of an effect is assessed with the Bayesian p-value and the difference in Leave-One-Out (LOO) criteria: positive value = greater fit. Results: The study cohort is composed of 12 female and 51 males with a median age of 45 years. Median CD4+ at the last visit was 164 [IQR: 80-390] and median estimated duration of infection (EDI) was 14 years [IQR: 10-19]. HIV DNA was detected in 69% of all brain and 100% of peripheral LT samples. BG had higher levels of HIV DNA (17.5 copies/106 cells) compared to FC (15.1, p=0.13) and OC (11.9, p=0.04). Females had higher levels of HIV DNA than males across all brain regions (p=0.05, Figure) but not in peripheral LT (P>0.2) after adjusting for CD4+, EDI, age and year of death. We found a robust significant interaction between sex, HIV DNA, and NC functioning (LOO Difference=1.4). Preliminary results indicate that increased HIV DNA differentially affected NC functioning in women and men, depending on the severity of the impairment. Conclusion: HIV DNA was detected in the majority of brains despite virologic suppression. While levels of HIV DNA were comparable in peripheral LT, women presented higher brain HIV DNA levels than men. These brain HIV reservoirs might differentially affect neurocognition in women and deserve investigation.

Poster and Themed Discussion Abstracts

CROI 2017 146