CROI 2025 Abstract eBook

Abstract eBook

Oral Abstracts

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Structural Brain Volumes Decrease After SARS-CoV-2 Infection Among People With HIV Jacob Bolzenius 1 , Ferron F. Ocampo 2 , Carlo Sacdalan 3 , Somchai Sriplienchan 3 , Luxe-Naree Poonpitak 3 , Napapon Sailasuta 4 , Julie Ake 5 , Donn Colby 5 , Phillip Chan 6 , Lydie Trautmann 7 , Sandhya Vasan 7 , Trevor Crowell 5 , Kilian Pohl 8 , Serena Spudich 6 , Robert Paul 1 , for the RV254/SEARCH 010 Study Team 1 University of Missouri St Louis, St Louis, MO, USA, 2 University of Toronto, Toronto, Canada, 3 SEARCH, Bangkok, Thailand, 4 University of Hawaii at Manoa, Honolulu, HI, USA, 5 United States Military HIV Research Program, Bethesda, MD, USA, 6 Yale University, New Haven, CT, USA, 7 Henry M Jackson Foundation, Bethesda, MD, USA, 8 Stanford University, Stanford, CA, USA Background: Healthy individuals who contract SARS-CoV-2 exhibit structural brain changes after infection. To assess whether SARS-CoV-2 is associated with unique or additive brain effects among people with HIV (PWH), we capitalized on systematic longitudinal 3T MRIs captured in the RV254 acute HIV (AHI) Thai cohort to compare changes between PWH who did or did not acquire SARS-CoV 2 infection. Methods: RV254 participants are enrolled and offered antiretroviral therapy (ART) during AHI. This analysis included PWH who underwent longitudinal 3T MRI, with the first scan acquired ≥5 months after ART initiation. Participants who then acquired SARS-CoV-2 (COVID+ PWH) between 2 scans were compared to those who completed >2 scans prior to 2020 and thus were SARS-CoV-2 naïve (COVID- PWH). Selected regions included those susceptible to SARS CoV-2 (olfactory cortex, superior frontal gyrus, orbital gyrus, gyrus rectus, hippocampus, and amygdala), and HIV (caudate, pallidum, putamen, thalamus, nucleus accumbens). Volumes were summed across hemispheres and corrected for head size. Longitudinal differences were assessed using a repeated measures MANOVA with a false discovery rate (FDR) correction for multiple comparisons. Results: Fifty RV254 COVID+ PWH (pre-COVID scan at median=5.6 years after

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Major Improvement in Age-Related Health Outcomes in People Living With HIV: A 18-Year Cohort Study Javier Martínez-Sanz 1 , Matilde Sánchez-Conde 1 , Jorge Díaz Álvarez 1 , Marta Rosas Cancio-Suárez 2 , Antoni Abdon Campins Rosselló 3 , Joaquim Peraire 4 , Juan Macias 5 , Xabier Camino Ortiz de Barrón 6 , María Saumoy 7 , Marta Herrero Romero 8 , Maria Jesus Perez Elias 1 , Santiago Moreno 2 , Alejandro Garcia 1 , Adrian Curran 9 , for the Cohorte de la Red de Investigación en Sida (CoRIS) 1 Hospital Ramón y Cajal, Madrid, Spain, 2 Hospital Universitario Ramon y Cajal, Madrid, Spain, 3 Hospital Universitari Son Espases, Palma, Spain, 4 Hospital Universitario de Tarragona Joan XXIII, Tarragona, Spain, 5 University of Sevilla, Sevilla, Spain, 6 Donostia University Hospital, San Sebastián, Spain, 7 Hospital Universitario de Bellvitge, Barcelona, Spain, 8 Hospital Universitario Virgen del Rocio, Sevilla, Spain, 9 Hospital Universitari Vall d'Hebron, Barcelona, Spain Background: Antiretroviral therapy (ART) has transformed HIV from a life threatening infection into a manageable chronic condition, allowing people living with HIV (PLWH) to have a significantly longer lifespan. However, as this population ages, they become increasingly susceptible to non-AIDS-related comorbidities typically associated with aging. Understanding the evolving patterns of these age-related conditions is essential to optimize care for this group. In this study, we analyzed trends in severe non-AIDS events (SNAEs) over different time periods to provide insights into how advances in HIV management have impacted the onset and frequency of these comorbidities.

Oral Abstracts

ART initiation) were compared to 16 COVID- PWH. Subgroups did not differ by age, CD4 count, or HIV RNA detection rate (overall median [IQR] baseline 27 [23-31] years, 632 [476-859] CD4+ cells/µL, 1.5% detectable); baseline CD4/ CD8 ratio was lower in COVID+ PWH ( p =.031). Volumetric trajectories differed significantly by group in the superior frontal ( p <.001), anterior orbital ( p =.014), and medial orbitofrontal (p=.043) gyri, and nucleus accumbens ( p =.037). Only the change between groups in the superior frontal gyrus remained significant after FDR correction ( p =.002), where COVID+ PWH had volumetric decreases (-339 mm3) while COVID- PWH exhibited increases (+393 mm 3 ). Conclusions: In the longitudinal RV254 study, participants acquiring SARS CoV-2 demonstrated evidence of structural brain changes over time compared to those followed prior to the COVID pandemic in regions susceptible to both conditions despite well-controlled HIV viremia. This implicates frontal gray matter in as a potential locus of SARS-CoV-2 impacts among PWH. Additional work will more fully evaluate temporal profiles and mechanisms of brain change relative to both conditions independently as well as their potential synergistic effect on brain integrity.

Methods: Using CoRIS, a Spanish multicenter prospective cohort with more than 20,000 PLWH, we defined three six-year periods: 2006–2011, 2012–2017, and 2018–2023. The primary outcome was a diagnosis of a severe non-AIDS event (SNAE) during follow-up. SNAE was defined as a composite event, including major adverse cardiovascular events (MACE), non-AIDS-defining malignancies, and non-accidental deaths. MACE included nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death. We used the Kaplan Meier method to plot the cumulative probabilities of events for each defined period. We used Cox proportional hazard models to assess the hazard ratios (HR) of events by period adjusted for age, sex, educational level, risk practice, geographic origin, CD4 nadir, baseline CD4/CD8, and baseline VL. We used linear regression to predict the mean age at first event in each period, using the same covariates. Results: A total of 18,659 ART-naïve participants were enrolled in the cohort between 2006 and 2023. The incidence of SNAEs in each period was 1.44 (95%CI 1.29-1.61), 0.95 (95%CI 0.83-1.08), and 0.67 (95%CI 0.57-0.79) per 1000 person years, respectively (p<0.001; Figure 1A). The adjusted HR for SNAEs compared to period 1 was 0.81 (95%CI 0.66-0.99) in period 2 and 0.58 (95%CI 0.45-0.73) in period 3. The adjusted predicted age for the first event was 42.2 (95%CI 39.8 44.6), 45.6 (95%CI 43.5-47.8), and 48.3 (95%CI 45.4-51.3) years, respectively (Figure 1B). Conclusions: The incidence of severe non-AIDS events among PLWH has decreased significantly over time, with a notable delay in the age of onset of these events. This could indicate that improvements in HIV treatment and care contribute to healthier aging in this population.

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CROI 2025