CROI 2025 Abstract eBook

Abstract eBook

Invited Session

newer agents, particularly bictegravir, dolutegravir and tenofovir alafenamide. This presentation will review the available evidence on weight gain in PWH, discuss potential treatment options and highlight research questions important to optimizing weight for PWH.

in HIV neuroinvasion, persistence, and neuroprotection. Recent data will show the establishment and maintenance of infected CD4 T cells in the brain from acute infection to ART-suppression, discuss the role of CD8 T cells in neuropathogenesis and mechanisms T cells play in both controlling HIV infection and the effects that lead to pathological consequences in the brain. Additional data will address the role of T cells during viral rebound after ART interruption and discuss how to harness T cells therapeutically to manage the consequences of HIV persistence in the brain. Dolutegravir Resistance: How Frequent Is It and How Will It Evolve? Nicaise Ndembi Africa Centres for Disease Control and Prevention, Addis Ababa, Ethiopia Background: Today's ART paradigm is characterized by the availability of potent drugs for HIV prevention and treatment, including second-generation integrase strand transfer inhibitors (INSTIs) like dolutegravir (DTG). INSTIs block the integration of viral DNA into the host genome, a critical step in HIV's life cycle. The integrase (IN) gene, a highly conserved region of the HIV genome, plays a key role in the virus's integration process and is targeted by INSTIs. Dolutegravir stands out for its superior efficacy, potency, high resistance barrier, and widespread use, particularly in resource-limited settings, making it a cornerstone of modern HIV treatment and a key contributor to achieving global epidemic control goals by 2030. The wide-scale adoption of DTG-based ART in RLS, coupled with limited treatment options in case of failure, highlights the need to closely monitor the emergence and spread of DTG resistance to ensure long-term and sustained efficacy. Furthermore, as the selection mechanism of drug resistance mutations (DRMs) is subtype-dependent, HIV-1 integrase resistance patterns as well as natural polymorphisms might display distinct pathways in the frame of a broad diversity of HIV-1 clades. We conducted a rapid review of recent literature (2023–2024) on global DTG resistance, analyzing 23 studies, including systematic reviews, scoping reviews, clinical trials, cohort studies, cross-sectional studies, and case reports. Overall, DTG resistance prevalence remains low: 0–1.9% in clinical trials, 0–14% in cohorts, and 0–27% in cross-sectional studies. Key mutations identified include R263K, G118R, N155H, and Q148H/R/K, with resistance influenced by prior treatment history and current formulations. Six scenarios were associated with DTG resistance: 3. ART-experienced individuals w/ virological failure (VF) on DTG & 2 NRTIs 4. ART-experienced individuals w/ virological suppression on DTG & 2 NRTIs 5. ART-experienced individuals w/ suppression on DTG & another ARV 6. ART-experienced individuals w/ suppression on DTG monotherapy Special considerations include (i) perinatally HIV-infected infants at risk of drug resistance from maternal ARVs or sub-therapeutic prophylaxis; and (ii) HIV/TB coinfected patients requiring careful regimen selection. DTG remains highly effective with a strong barrier to resistance. While resistance rates are encouragingly low, ongoing surveillance is crucial. Dolutegravir Resistance: What Are the Implications for Antiretroviral Therapy Programs? Jeremy Nel University of the Witwatersrand, Johannesburg, South Africa Background: DTG-based regimens have simplified management for providers: 1. Resistance to 1st-line DTG-based regimens is still incredibly rare. Therefore limited role for resistance testing in this scenario; can mostly assume non-adherence if viral load elevated. Fewer resistance tests required; less unnecessary switching drug classes, esp. in LMIC. 2. “Blind” switching to DTG-based regimens without requiring a resistance test has also been feasible in many cases. This has allowed regimen simplification & better outcomes. Implications for monitoring 1. More frequent resistance testing will be required. A. Will show an example from WHO/SA context of how thinking is changing. B. Cost implications (will show an estimate) 1. 2. ART-naïve individuals on DTG w/ 2 NRTIs ART-naïve individuals on DTG w/ lamivudine (dual therapy)

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Multiomics in the Brain Howard Fox University of Nebraska, Omaha, NE, USA Background

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Invited Session

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The Central Nervous System Reservoir: Impact for Cure and Ongoing Neuropathology Melissa Churchill Royal Melbourne Institute of Technology, Melbourne, Australia Background: HIV persists in the central nervous system (CNS), and a subset of PWH develop neurocognitive issues despite virally suppression. With a diverse set of infected cells comprising the CNS reservoir, along with the impact of both acute and chronic infection on local inflammation and blood brain barrier integrity, the CNS presents an important and unique challenge, not only for ongoing management, but importantly for cure strategies. Studies have demonstrated the CNS reservoir resides predominantly in resident microglia, the role of astrocytes, resident and circulating T cells is less clear. HIV genomes in the CNS are transcriptionally/translationally active despite viral suppression with transcriptional products and viral proteins detected. As reported for peripheral reservoirs, defective proviral genomes predominate in the CNS in both virally suppressed and viremic PWH. The function of these defective genomes remains unclear, but likely contribute to ongoing neuroinflammation. The frequency of infected cells within the brain is reported to be very low, however, in the cerebrospinal fluid (CSF), levels of cell free virus and HIV+ T cells have been associated with adverse neurological outcomes in PWH. The source of cell free CSF virus remains unclear. With the advent of cure strategies involving activation of virus either by removal of ART or by the administration of latency reversal agents (LRAs) the ability of these strategies to access and impact the CNS is critical. Some LRAs can cross the blood brain barrier (BBB) with little toxicity observed and are capable of activating brain derived HIV in vitro, however, the impact of activating the brain reservoir on local inflammation is less clear. The restrictive nature of BBB may impact other current strategies including immunotherapy and gene therapy approaches; therefore, effectiveness and adverse CNS effects needs consideration. Currently, the development of cure strategies focuses primarily on effectiveness and impacts on the peripheral blood and tissue reservoirs. Clinical trials in both non-human primates (NHPs) and PWH have largely failed to include consideration and analysis of impacts on the CNS. It is critical that future cure strategies consider the CNS and include PWH with a greater predisposition for poor HIV associated neurological outcomes. In this presentation we will discuss the nature and impact of the CNS reservoir, its role in ongoing neuropathology and the potential impact of cure strategies.

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Emerging Role of T Cells in the Central Nervous System Lydie Trautmann Henry M Jackson Foundation, Bethesda, MD, USA

Background: This presentation will address how T cell and specific T cell subsets are revealing new insights in neuroHIV pathogenesis, specifically

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CROI 2025