CROI 2019 Abstract eBook

Abstract eBook

Poster Abstracts

408 LONGITUDINAL PHENOTYPING OF DECLARATIVE MEMORY AMONG WOMEN LIVING WITH HIV Kathryn Fitzgerald 1 , Pauline M. Maki 2 , Yanxun Xu 3 , Wei Jin 3 , Gayle Springer 4 , Kathryn Anastos 5 , Deborah Gustafson 6 , Seble Kassaye 7 , Victor Valcour 8 , Leah H. Rubin 1 1 Johns Hopkins University School of Medicine, Baltimore, MD, USA, 2 University of Illinois at Chicago, Chicago, IL, USA, 3 Johns Hopkins University, Baltimore, MD, USA, 4 Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA, 5 Albert Einstein College of Medicine, Bronx, NY, USA, 6 SUNY Downstate Medical Center, Brooklyn, NY, USA, 7 George Washington University, Washington, DC, USA, 8 University of California San Francisco, San Francisco, CA, USA Background: There is considerable heterogeneity in patterns of cognitive decline in HIV-infected (HIV+) individuals. Age, sex, and race contribute to individual differences in patterns of cognitive decline, including in the domain of verbal memory. Advanced statistical models can be applied to parse out the heterogeneity in cognitive decline and to identify subgroups of individuals who might benefit from interventions tailored to their particular pattern of change and risk factors. Here, we applied a novel statistical method to identify clusters of individuals with distinct patterns of age-related change in declarative memory in HIV+ and HIV-uninfected (HIV-) women. Methods: We included 1530 women from the Women’s Interagency HIV Study who completed the Hopkins Verbal Learning Test at two or more visits. To derive subgroups with similar patterns of decline by HIV-serostatus, we applied a novel modeling strategy that simultaneously considers multiple longitudinal declarative memory outcomes. This model adopts a linear mixed-effects framework to model the trajectory of each cognitive outcome over time, while also jointly clustering individuals via a factor analysis model. We tested for differences in demographic and clinical characteristics between the clusters using a multivariable-adjusted multinomial model. Results: Of the 1530 included participants, 1167 were HIV+ (69% African- American [AA]; 31%white/other [W/O]) and 586 were HIV- (68% AA; 32%W/O). Stratification by race was necessary to optimize clustering. In the HIV+ AA’s, we identified four distinct subgroups with differential patterns of change in memory: a subgroup with minimal decline, two with accelerated decline, and a subgroup with stable impairment in learning and memory ( Fig 1A ). In the HIV- AA’s, we identified three subgroups: one with lesser decline and two with accelerated decline ( Fig 1B ). In multivariable adjusted models, individuals with accelerated decline were more likely to be less educated (P<0.001) and have a history of depression (P<0.001) versus those in the minimal decline subgroups ( Fig 1C ). Similarly classified subgroups were identified in W/O HIV+ and W/O HIV- participants. Conclusion: Our data-driven modeling approach successfully identified clinically meaningful subgroups of individuals with distinct phenotypes of declarative memory decline. Depression was a key, potentially modifiable determinant of membership in a subgroup characterized by more rapid decline.

1 Johns Hopkins University School of Medicine, Baltimore, MD, USA, 2 Johns Hopkins University, Baltimore, MD, USA, 3 Blood Systems Research Institute, San Francisco, CA, USA, 4 Albert Einstein College of Medicine, Bronx, NY, USA, 5 University of Illinois at Chicago, Chicago, IL, USA, 6 Georgetown University, Washington, DC, USA, 7 SUNY Downstate Medical Center, Brooklyn, NY, USA, 8 University of California San Francisco, San Francisco, CA, USA Background: Neurocognitive (NC) impairment persists even among those who are virally suppressed. Virally suppressed women living with HIV (WLWH-VS) demonstrate vulnerabilities across multiple cognitive domains. As there is strong scientific premise for immunological processes contributing to cognitive status, we examined the contribution of early neuroinflammatory profiles to future NC performance. Methods: We selected 49 WLWH who achieved and maintained viral suppression shortly after effective antiretroviral (ARV) initiation, along with a matched sample of 56 HIV- women from the Women’s Interagency HIV Study. Peripheral levels of 42 inflammatory markers were measured using stored samples fromwithin two years of ARV initiation and 1, 7, and 12 years later. 27/49 WLWH-VS and 35/56 HIV- women completed NC testing (e.g., learning, memory, attention) following the 12 year follow-up at ≥1 time points. We searched for latent immune profiles (underlying patterns of marker changes) by adapting a dynamic matrix factorization analytic method that builds upon Tucker decomposition. We calculated the Frobenius residual to choose the number of components and named them based on the markers that contributed the most to each one. We used mixed-effects models to examine changes in immune components over time, which were subsequently correlated with domain-specific (e.g., learning, memory) and global NC performance. Results: Seven latent immune components emerged for WLWH-VS and HIV- women. Immune components 1-4 were common across groups (e.g., immune activation and vascular dysfunction) whereas components 5-7 were distinct (Fig 1A). Early inflammatory profiles predicted subsequent NC performance in both groups but more associations were significant in WLWH-VS (47%) versus HIV- women (20%)(Fig 1B&C). Among WLWH-VS, immune components reflecting greater T-cell recruitment and neuroprotection predicted worse global performance whereas components reflecting oxidative stress and metabolic function predicted domain-specific performance. Among HIV-, immune components predicted global versus domain-specific performance. Conclusion: Seven latent immune components emerged for WLWH-VS and HIV- women. Immune components 1-4 were common across groups (e.g., immune activation and vascular dysfunction) whereas components 5-7 were distinct (Fig 1A). Early inflammatory profiles predicted subsequent NC performance in both groups but more associations were significant in WLWH-VS (47%) versus HIV- women (20%)(Fig 1B&C). Among WLWH-VS,

Poster Abstracts

409 CAPTURING DNA METHYLATION CHANGES IN MONOCYTES WHEN INITIATING ART IN ACUTE HIV

Michael J. Corley 1 , Carlo Sacdalan 2 , Elizabeth Laws 1 , Nitiya Chomchey 2 , Alina P. Pang 1 , Nisakorn Ratnaratorn 2 , Ivo N. SahBandar 1 , Victor Valcour 3 , Eugène Kroon 2 , Robert Paul 4 , Merlin L. Robb 5 , Jintanat Ananworanich 5 , Lishomwa C. Ndhlovu 1 , for the SEARCH010/RV254 and SEARCH013/RV304 study groups

CROI 2019 147

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