CROI 2024 Abstract eBook

Abstract eBook

Poster Abstracts

Results: Cohort characteristics: mean age 53 years, 17% women, 59% White, median CD4+ T-cells 615/µL, 66% AIDS, and nearly all were seropositive for CMV (96.5%) and EBV (100%). CMV DNA was detected in PBMCs in 47.8%, EBV DNA in 95.6%, and HIV DNA in 99.2%. In simple regression, VACS was positively associated with CMV IgG (p<0.001), HIV DNA (p=0.013), EBV DNA (p=0.003), and EBV IgG (p=0.001). In adjusted models, VACS remained associated with CMV IgG (p=0.017, R2= 0.46) and HIV DNA (p=0.07, R2=0.45). VACS was not associated with CMV DNA. CMV IgG was associated with EBV IgG (p=0.008), but not HIV, CMV, or EBV DNA. Conclusion: While limited by cross-sectional, observational design, our findings suggest the immune response to CMV (measured by IgG titers) is a more important predictor of adverse clinical outcomes in PWH than levels of CMV DNA in PBMCs. This may reflect the need for tissue level DNA or the immune dysregulation triggered by CMV may not be directly related to the burden of CMV. While CMV IgG correlated with EBV IgG levels, only CMV IgG was a significant predictor of VACS scores when adjusting for key confounders. This adds support for a CMV specific effect, rather than general hyperglobulinemia. Additional investigation is needed to identify potential therapeutic interventions and assess the relationship with CMV DNA within tissues. The figure, table, or graphic for this abstract has been removed. Changes in HAND Prevalence Among Medicaid Enrollees From 2016-2021 in the US Kashif Iqbal , Tiffany Williams, Jesse G. O'Shea, Kate Buchacz Centers for Disease Control and Prevention, Atlanta, GA, USA Background: HIV-associated neurocognitive disorder (HAND) is a range of progressively severe central nervous system complications associated with HIV infection. The range can be from mild problems with memory, language, and reasoning to the more severe HIV-associated dementia. HAND has declined with the advancement of antiretroviral therapy (ART), however, remains prevalent in older people with HIV (PWH). We describe the prevalence of HAND among PWH among Medicaid enrollees in the U.S. from 2016-2021. Methods: We analyzed data from Truven Health MarketScan Claims and Encounters®, a large database derived from administrative claims for healthcare services provided to Medicaid enrollees. Among enrolled persons aged >18 years, we identified PWH with at least one inpatient or outpatient medical claim with an HIV and subsequent major to mild neurocognitive disorders (NDs) ICD-10-CM diagnosis codes. We used chi-square to compare PWH with an associated NDs diagnosis (HAND) to those without an associated ND diagnosis code (no-HAND) to investigate differences in HAND prevalence by age, sex, race/ ethnicity, and by prescribed ART from 2016-2021. Results: The annual crude prevalence of HAND ranged from 1.6% (512/31,897) in 2016 to 1.9% (558/29,967) in 2020. The prevalence of HAND significantly increased with age (p-value<0.001); highest prevalence was among ages 65+ years (range 3.7% in 2021;5.7% in 2017). Males had a significantly higher prevalence of HAND compared to females in 2016 (1.8% vs 1.4%; p-value= 0.007) and 2017 (1.9% vs 1.6%; p-value= 0.027) but from 2018-2021 there were no differences by sex. In 2016 and 2020 there were differences by race/ethnicity (p-value= 0.0002 and 0.001 respectively), with the highest prevalence of HAND among White persons in 2016 (1.9%) and Black persons in 2020 (2.1%) Among the 190,648 PWH from 2016-2021, the frequency of ART prescriptions ranged from 58% (18,671/31,897) in 2016 to 64% (21,018/32,820) in 2021. Prevalence of HAND was significantly higher among persons without an ART prescription (range 1.8% in 2016-2.2% in 2020) compared to those with an ART prescription (range 1.1% in 2021-1.7% in 2020) for each year (Figure). Conclusion: In this large administrative database of PWH, HAND remains persistent, with some demographic disparities. With the aging population of PWH, strengthening interventions that improve access to ART, promote adherence, and address barriers to clinical care and supportive services for PWH is critical for reducing health disparities.

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VACS 2 0 Shows Improved Discrimination of Neurocognitive Impairment and Frailty in People With HIV Cynthia Yan , Sarah Cooley, Beau Ances Washington University in St Louis, St Louis, MO, USA Background: The Veterans Aging Cohort Study (VACS) 1.0 Index is a generalizable risk index that combines and weights age, CD4 count and human immunodeficiency virus (HIV) type 1 RNA alone (Restricted Index), hemoglobin, FIB-4 Index, hepatitis C virus, and estimated glomerular filtration rate. The VACS 1.0 index more accurately discriminates mortality risk among persons with HIV (PWH) prescribed antiretroviral therapy than traditional HIV markers and age alone. More recently, there have been revisions to VACS 1.0 index. This study examined whether the updated VACS 2.0 index (including serum albumin, body mass index (BMI), and white blood cell (WBC) count) had stronger correlations with cognitive function, brain volume, and frailty in older (≥50 years) PWH compared to the original VACS 1.0. Methods: Neuropsychological performance (NP) Z-scores (learning, retention, executive functioning (EF), psychomotor function/processing speed (PM/ PS), language, and global cognition), and neuroimaging measures (brain volumetrics) were analyzed in PWH (n=162, 88.17% male). A subset of the sample (n = 159) was defined as either frail (n = 18) or non-frail (n = 141) according to the Fried phenotype criteria. Brain volumes, NP scores, and frailty subgroups were analyzed with both VACS scores, albumin, BMI, and WBC count using Pearson's significance tests and independent T-tests. Results: Based on values shown in Table 1, higher VACS scores significantly correlated with lower brain volumes. A higher VACS 2.0 score was associated with lower NP in the EF and PM/PS domains and was primarily driven by albumin. In contrast, VACS 1.0 scores did not correlate with cognition Z-scores. There was no relationship between frailty status and VACS 1.0. PWH who were frail had significantly greater VACS 2.0 scores than non-frail PWH. Conclusion: The addition of serum albumin to the VACS index improved its correlations with NP and frailty in PWH. While low albumin levels may contribute to cognitive decline or frailty, the reverse causality should also be considered. For example, those with frailty or cognitive impairment may struggle to maintain proper nutrition, potentially resulting in decreased albumin levels. Regardless of the direction of causality, these findings suggest that the VACS 2.0 index and albumin are valuable measures for clinicians to improve outcomes in older PWH. Latent Viral Infections Are Associated With Veterans Aging Cohort Study Index in People With HIV Patricia K Riggs , Gordon Honerkamp Smith, Milenka Meneses, Antoine Chaillon, Gemma Caballero, Donald Franklin, Robert K. Heaton, Ronald J. Ellis, Background: People with HIV (PWH) on ART have elevated risk for mortality, frailty, and cognitive impairment. The Veterans Aging Cohort Study (VACS) index is a validated risk score associated with these outcomes in PWH. CMV and EBV coinfections have been implicated in these outcomes and expansion of the HIV reservoir but it is unknown if this is a direct effect of the virus or the immune response. We sought to determine the relationships among quantitative cell associated viral DNA, IgG levels, and VACS index score. Methods: Participants included 485 PWH with comprehensive neuromedical testing, HIV RNA<200 copies/mL on antiretroviral therapy, and stored blood. Digital droplet PCR quantified cell associated CMV, EBV, and HIV DNA in peripheral blood mononuclear cells (PBMCs). EBV VCA IgG and CMV IgG were measured in plasma by ELISA. Using linear regression, we tested the associations between VACS and viral DNA and IgG levels. Model estimates were adjusted for age, sex, race/ethnicity, estimated duration of HIV (EDI), CD4+ T-cells, and AIDS diagnosis. Scott L. Letendre, Sara Gianella Weibel University of California San Diego, San Diego, CA, USA

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CROI 2024 167