CROI 2025 Abstract eBook

Abstract eBook

Poster Abstracts

626

Reduced Cerebral Arterial Transit Time in Obese Females With HIV and Metabolic Syndrome Eric Decloedt 1 , Md Nasir Uddin 2 , Chantel Schreuder 3 , Lauren Jennings 3 , Roland van Rensburg 1 , Ankia Coetzee 1 , Abrar Faiyaz 2 , Nhat Hoang 2 , Catherine Orrell 4 , Giovanni Schifitto 2 1 Stellenbosch University, Cape Town, South Africa, 2 University of Rochester Medical Center, Rochester, NY, USA, 3 Desmond Tutu HIV Foundation, Cape Town, South Africa, 4 University of Cape Town, Cape Town, South Africa Background: The prevalence of obesity, and subsequent metabolic syndrome (MetS), is increasing in persons living with HIV (PLWH) on antiretroviral therapy (ART), with nearly 1 in 4 meeting MetS criteria. African females with HIV are at particular risk of developing obesity complicated by MetS. Obesity increases the risk of cardiovascular and cerebrovascular disease. There is limited data on the association of obesity and MetS in PLWH with biomarkers of cerebrovascular function such as cerebral blood flow (CBF), arterial transit time (ATT), cerebrovascular reactivity (CVR) and microcirculation as measured by intravoxel incoherent motion (IVIM) metrics (diffusion, D; pseudo-diffusion, D*; and perfusion fraction, f). Methods: We conducted a cross-sectional study of PLWH at a primary care clinic in Cape Town, South Africa, suppressed on ART and newly diagnosed with MetS using the Harmonized criteria. Our primary outcome was to assess CVR, derived from resting state functional magnetic resonance imaging, CBF, ATT and water exchange rate Kw assessed via diffusion-prepared multi-delay arterial spin labelling. Brain volumetrics were assessed via T1 weighted imaging, processed with FreeSurfer. Using linear regression, we correlated our imaging findings with a composite MetS severity z-score and body fat composition quantified using dual-energy X-ray absorptiometry (DEXA). Results: We enrolled 27 female participants aged 45.2±10 years with a body mass index (BMI) of 41.9±7.8 kg/m 2 . We found no association between CVR, ATT, Kw, CBF or brain volume in gray and white matter and the MetS z-score based on BMI or waistline. ATT in both gray and white matter was significantly increased with higher body mass indices. Both gray and white matter ATT increased with higher waist circumference, body fat mass, body fat percentage and visceral adipose tissue mass, with body fat percentage most striking (β=16.4, p = 0.012 and β=16.3, p = 0.009, respectively). D* in gray matter was associated with MetS severity z-score based on BMI and waistline (r=0.57, p = 0.005 and r=0.42, p = 0.047, respectively) and body fat mass (r=0.47, p=0.026 in white matter, r=0.44, p=0.035 in gray matter). Conclusions: ATT is an index of vascular resistance that increases in the presence of cerebrovascular disease. We found that in obese African females with HIV and MetS suppressed on ART, ATT increases in proportion to body fat percentage. This finding is also reflected in alterations of the microcirculation, as measured by the IVIM metric D*. HIV Transcripts in Blood May Identify Patients at Lower Risk of Brain Injury in Cure Research Kazuo Suzuki 1 , Angelique Levert 1 , Emma Yoo 1 , Lucette A. Cysique 2 , Takaomi Ishida 3 , Nicholas Olsen 4 , Louise Evans 5 , Bruce Brew 6 , John Zaunders 1 St Vincent's Centre for Applied Medical Research, Darlinghurst, Australia, 2 University of New South Wales Sydney, Sydney, Australia, 3 Denka Co Ltd, Tokyo, Japan, 4 University of New South Wales, Darlinghurst, Australia, 5 Liverpool Hospital, Liverpool, Australia, 6 St Vincent's Hospital, Sydney, Australia Background: Suppressed HIV patients’ PBMC have residual cell associated HIV-1 RNA transcripts (HRT). Elevated HRT, despite ART, associate with viral blips and with brain injury. Most cure studies aim to reduce HIV DNA reservoir but may require initial viral reactivation, risking brain injury from viral blips due to reservoir activity. Under ART, blips are believed to reflect reservoir size, but whether they could be independently due to reservoir activity is unclear. Current understanding of blips does not allow prediction of viral blips. We hypothesized that HRT levels measured by the Double R assay may predict risk of blips, helping identify low risk patients for cure studies. Methods: RNA and DNA were extracted from cells from 5 ml blood samples from 64 patients on suppressive ART at baseline and sequentially for 4y. Of these, 32 had 1 or 2 blips (isolated detectable pVLs <200 cp/ml in the 2y prior to baseline), 29 had no blips, and 3 were Elite Controllers (to serve as benchmarks of functional cure). HRT was measured by the Double R assay. Multivariable mixed-effects logistic regression was used to predict any future blip over 4y. A cut-off value of HRT was determined using Youden’s index with Receiver Operator Characteristic (ROC) curves.

towards improved TrA in participants with baseline impairment randomized to pitavastatin (Z score [95% CI]: 0.075 [0.024, 0.127]) vs placebo (-0.05 [-0.123, 0.023]), p=0.018 and towards worsened NPZ-4 in females randomized to pitavastatin (-0.061 [-0.133,0.011]) vs placebo (0.033 [-0.023, 0.089]), p=0.068 that similarly did not reach threshold for clinical relevance. Other subgroup effects were minimal and not statistically or clinically significant. Conclusions: We found no evidence to suggest a detrimental effect of pitavastatin on a limited battery of neurocognitive assessments among people with HIV at low to moderate cardiovascular risk, even among those with baseline impairment.

625

Number and Effectiveness of Antihypertensives Are Associated With Cognitive Performance in PWH Azin Tavasoli 1 , Bin Tang 2 , Scott L. Letendre 2 , Robert K. Heaton 2 , Ronald Ellis 1 1 University of California San Diego Medical Center, La Jolla, CA, USA, 2 University of California San Diego, La Jolla, CA, USA Background: People with HIV (PWH) experience age-related health problems, including cardiovascular disease and cognitive decline. Some medications used to treat hypertension exhibit anticholinergic properties. This study investigated the effects of cognitive performance on antihypertensive use and mean arterial pressure (MAP) in hypertensive PWH and people without HIV (PWoH), focusing on whether worsening cognitive function influenced antihypertensive use and blood pressure control. Methods: This longitudinal analysis spanned up to seven follow-up visits in multisite, observational cohort studies over five years. Participants were included if they reported hypertension or used antihypertensive medications. Analyses examined the relationship between cognitive performance (global T-score) and the number of antihypertensives reported over time, including a linear mixed effects model with random intercepts and slopes, stratified by HIV status and adjusted for confounding variables such as age, sex, ethnicity, body mass index (BMI), and HIV disease markers. We also analyzed the relationship between summary regression change score (sRCSs) and MAP. Results: The 1158 PWH with hypertension were mostly middle-aged, white, and male. 79.9% were on antiretroviral therapy (ART); 59.7% had plasma HIV RNA ≤ 50 copies/ml. PWoH (n=272) were older than PWH and more likely to be female. In PWH, a significant association between MAP and sRCSs suggested those with greater cognitive improvement had lower MAP (multivariable analysis p=0.0498). In PWH, a 10-unit decrease in global T-score (worsening cognitive performance) was associated with an 8.7% increase in the number of antihypertensives over time (univariable analysis RR=0.916, p=0.027; multivariable analysis RR=0.907, p=0.014). lagged effects of global T-score on antihypertensives were not significant in both PWH and PWoH. A higher number of anticholinergics correlated with the number of antihypertensives (β= 0.45, p=0.001). PWH taking more anticholinergics were more likely to have worse cognitive performance over time (p<0.001). Conclusions: Our findings suggest that healthcare providers may prescribe more antihypertensives to PWH whose cognitive performance declines over time, possibly due to inadequately controlled high blood pressure. Antihypertensives can have anticholinergic effects that may worsen cognitive decline. Conversely, PWH with cognitive improvement had lower MAP, suggesting better blood pressure control may be linked to enhanced cognitive function.

Poster Abstracts

627

CROI 2025 171