CROI 2025 Abstract eBook

Abstract eBook

Poster Abstracts

Conclusions: Declines in NHL may be due to improved immunity at HIV diagnosis, earlier ART initiation and greater effectiveness over time. Declining lung cancer is observed in other studies of PWH, but drivers for this and sex differences remain unclear (though possibly related to greater decline in smoking rates in men versus women). Increasing breast/prostate cancer merits continued monitoring at the population/individual-level and to further investigate the impact of screening, aging and other factors driving burden of these cancers. Cancer trends in women underscore the need to clarify cancer etiology and improve screening for women with HIV.

previously published RNA-Seq data from cancerous skin KS versus matched normal tissue (n=10 patients) we found the pro-angiogenic vascular endothelial growth factor receptor-3 (VEGFR3/FLT4) significantly upregulated 7-fold ± 1.2. This induction was more pronounced in cell culture with a 50-fold increase after KSHV lytic reactivation. FLT4 signaling pathways promote cell proliferation, migration, and angiogenesis, and dysregulated expression is linked to various cancers, but it’s role in KSHV infection remains unknown. Methods: To probe the role of FLT4 in infection, we performed siRNA depletion of FLT4 in primary lymphatic endothelial cells (LEC) prior to KSHV infection (MOI ~1). We measured viral replication by transcript and protein expression, genome replication, and virion production. We determined significance by paired T-tests between a non-targeting control and the siRNA targeting FLT4. We also performed RNA-sequencing of knockdown samples to interrogate the host transcriptional landscape upon VEGFR3 depletion. Results: We observed significant increases in lytic replication upon FLT4 depletion with increases in viral genome replication (2-fold), viral transcripts and protein (1.5-fold), infectious progeny (4-fold), and nascent particles (10 fold) with no change in viral entry. RNA-sequencing of FLT4-depleted samples revealed enrichment for host genes involving cell contact and communication. Pathway analysis showed inhibition of angiogenic and tumor progression signaling, including FAK signaling and Molecular Mechanisms of Cancer. Conclusions: These data suggest that FLT4 may be suppressing lytic infection yet promoting tumorigenesis. We propose a model in which FLT4 is impeding lytic replication such that KSHV preferentially enters latency where it can more favorably drive pro-angiogenic processes. As such, we are investigating the use of FDA-approved VEGFR inhibitors on the viral life cycle and plan to assess effects on host proliferation and pro-angiogenic processes as a new potential strategy to inhibit KSHV-driven disease. Trends in Common Cancer Diagnoses Among People With HIV in North America, 2006-2020 Sally B. Coburn 1 , Elizabeth Humes 1 , Michael Horberg 2 , Michael Silverberg 3 , Jeffrey Martin 4 , Raynell Lang 5 , Chad Achenbach 6 , Lesley Park 7 , Minh Ly T. Nguyen 8 , Mari Kitahata 9 , Maile Karris 10 , Heidi M. Crane 9 , Joseph J. Eron 11 , Keri N. Althoff 1 , Richard Moore 1 , for the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) of IeDEA 1 The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA, 2 Kaiser Permanente Mid-Atlantic States, Rockville, MD, USA, 3 Kaiser Permanente Northern California, Oakland, CA, USA, 4 University of California San Francisco, San Francisco, CA, USA, 5 University of Calgary, Calgary, Canada, 6 Northwestern University, Chicago, IL, USA, 7 Stanford University, Stanford, CA, USA, 8 Emory University, Atlanta, GA, USA, 9 University of Washington, Seattle, WA, USA, 10 University of California San Diego Medical Center, La Jolla, CA, USA, 11 University of North Carolina at Chapel Hill, Chapel Hill, NC, USA Background: Cancer burden among people with HIV (PWH) has shifted from cancers associated with immunodeficiency to cancers common in the general population. Trends in common cancer diagnoses by sex have not been adequately characterized following the introduction of Treat-All policies and modern ART regimens. We examined incidence trends by sex for common cancers in a consortium of PWH in care from 2006-2020 in the US and Canada. Methods: We estimated sex- and period-specific cancer incidence rates (2006 10; 2011-15; 2016-20) per 100,000 person-years (PY) among PWH participating in the North American AIDS Cohort Collaboration for Research and Design (NA-ACCORD) in cohorts contributing validated cancer diagnoses. We report on the 5 most common cancer diagnoses (excluding non-melanoma skin cancer) by sex: Non-Hodgkin lymphoma (NHL), lung, anal; head/neck and prostate for men; and breast and cervical for women. We age-standardized incidence rates to the US 2000 population. Results: Among 112,757 PWH (86% men, 14% women) in 20 NA-ACCORD cohorts, we included 4,634 incident cancer diagnoses. Median age at first cancer diagnosis was 60 years (IQR 54, 66) for men and 51 (IQR 44, 58) for women. NHL declined over time in men (111-55 cases per 100,000 PY, p<0.05) and women (80-41 cases per 100,000 PY p <0.05). Head/neck cancers were stable in men (mean: 54 cases per 100,000 PY, p>0.05). Cervical cancer was stable (mean: 53 cases per 100,000 PY, p>0.05) over time. Lung cancer declined in men (151-92 cases per 100,000 PY, p<0.05) but was stable in women (90-95 cases per 100,000 PY, p>0.05). Anal cancer was stable in men over time (65-76 cases per 100,000 PY, p>0.05) but increased in women (11-27 cases per 100,000 PY, p<0.05). Breast and prostate cancers were stable or declined from 2006-10 to 2011-15 but had non-significant (p>0.05) increases from 2011-15 to 2016-20.

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Cancer Risk of People With HIV Younger Than 50 Years: Italy, 1997-2023 Camilla Muccini 1 , Pierluca Piselli 2 , Claudia Cimaglia 2 , Alessandra Bandera 3 , Giulia Marchetti 4 , Valentina Mazzotta 2 , Luca Pipitò 5 , Alessandro Tavelli 6 , Stefano Rusconi 4 , Carlo-Federico Perno 7 , Enrico Girardi 8 , Antonella d'Arminio Monforte 6 , Diego Serraino 9 , Antonella Cingolani 10 , for the Icona Foundation Study Group 1 IRCCS San Raffaele Scientific Institute, Milan, Italy, 2 National Institute for Infectious Diseases L Spallanzani, Rome, Italy, 3 IRCCS Fondazione Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy, 4 University of Milan, Milan, Italy, 5 University of Palermo, Palermo, Italy, 6 Icona Foundation, Milan, Italy, 7 Bambino Gesu Children's Hospital, Rome, Italy, 8 IRCCS Lazzaro Spallanzani, Rome, Italy, 9 CRO Aviano National Cancer Institute, Aviano, Italy, 10 Universita Cattolica del Sacro Cuore, Milan, Italy Background: People with HIV (PWH) have an increased risk of cancer compared to the general population, even under antiretroviral therapy (ART); however, specific data in young PWH are lacking. Aim of the study was to assess the cancer risk of PWH aged <50 years in Italy. Methods: Observational study in the Icona cohort enrolling ART-naïve PWH. All participants <50 years at enrolment (Jan1997/Dec 2023) were included. Incident cancers (excluding non-melanoma skin cancers) were categorized as AIDS-defining (ADMs: Kaposi's sarcoma, KS; non-Hodgkin's lymphoma, NHL; invasive cervical cancer, ICC) or non AIDS-defining (NADM: virus and non-virus related). Standardized incidence ratios (SIRs) as risk estimate were calculated by multiplying the person-years (PYs) at risk in PWH by the corresponding specific incidence rates from all Italian cancer registries. SIRs were standardized by sex, age, residence, calendar period. Results: 14,060 PWH were included, contributing to 94,607 PYs of follow up. Overall, 78.7% were men, with a median age of 35 years (interquartile range, 29-41). Overall, 400 (2.8%) PWH developed at least one de novo cancer (229 ADMs, 177 NADMs) during follow-up. PWH had a 2.9-fold increased risk for all cancers compared with the general population (95% CI: 2.6-3.2, Table 1; SIR=3.5 in males and 1.7 in females). Significantly elevated SIRs were observed for ADMs overall (SIR=20.8) and for individual cancer: KS (SIR=186.9), NHL (SIR=6.6), and ICC (SIR=9.3). A 9.4-fold risk increase was noted for virus related NADMs, particularly for anal cancer (SIR=71.7) and Hodgkin lymphoma (SIR=9.2). No evidence for a difference in risk was observed for non virus-related NADMs overall (SIR=0.9, 95% CI: 0.7-1.1), with decreased risks for leukaemia, bladder (SIR=0.5), skin melanoma, and thyroid cancer (SIR=0.6); a significant risk reduction was reported only for breast cancer (SIR=0.5). Conversely, a significant increased risk was observed for trachea/bronchus/lung cancer (SIR=3.2). Conclusions: In PWH <50 years old, cancer risk is almost 3-times higher than in the comparable general population. Higher frequencies of coinfections, smoking and HIV-related chronic inflammation might explain these findings.

Poster Abstracts

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CROI 2025 238