{"title":"Modeling the fallout: projecting the global impact of donor funding cuts on HIV prevention, treatment, and care.","authors":"Jirair Ratevosian, Paul Ngangula, Khai Hoan Tram","doi":"10.1097/COH.0000000000000977","DOIUrl":"10.1097/COH.0000000000000977","url":null,"abstract":"<p><strong>Purpose of review: </strong>Recent U.S. funding cuts and subsequent terminations to global HIV programs threaten decades-long progress towards ending the HIV epidemic. In response to financial and programmatic uncertainty, mathematical models have projected dire consequences of current and future reductions in aid. This review examines modeling studies published from 20 January through 30 May 2025 and presents a comparative analysis of model estimates and synthesizes key findings.</p><p><strong>Recent findings: </strong>Nine modeling studies examined U.S. and international donor funding reduction scenarios, ranging from a temporary pause to indefinite termination, with most analyses focused on sub-Saharan Africa and PEPFAR-supported programs. Time horizons varied from short-term projections (2025-2026) to long-term estimates spanning the next 20 years. Geographic coverage differed across studies, with some models focused on individual countries (e.g., South Africa) and others projecting outcomes across all low- and middle-income countries (LMICs). Based on consensus projections, global donor funding cuts - including those proposed by the Trump administration - could result in 10 million additional HIV infections, including 1 million among children, and 3 million additional deaths over the next 5 years.</p><p><strong>Summary: </strong>Early modeling studies converge on a clear message, that even partial reductions in external HIV funding pose the risk of reversing decades of progress, with disproportionate effects in high-burden countries reliant on PEPFAR funding. However, estimates vary widely due to heterogenous model structures and varying assumptions regarding funding cuts and adaptability of programs. These models should be interpreted as directional tools to guide decision-making, offering policymakers a tool to assess funding scenarios and anticipate potential consequences. For national governments, the models underscore the urgent need for sustained investment in HIV mitigation programs.</p>","PeriodicalId":93966,"journal":{"name":"Current opinion in HIV and AIDS","volume":" ","pages":"621-631"},"PeriodicalIF":4.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144983821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Mapping the anatomical distribution and persistence of HIV-infected cell clones in tissues: implications for HIV cure strategies.","authors":"Marion Pardons","doi":"10.1097/COH.0000000000000970","DOIUrl":"10.1097/COH.0000000000000970","url":null,"abstract":"<p><strong>Purpose of review: </strong>This review summarizes recent literature about current approaches to track HIV-infected T cell clones, their anatomical distribution and phenotypic features under antiretroviral therapy (ART) suppression, as well as the implications of clonal expansion for HIV cure strategies.</p><p><strong>Recent findings: </strong>Multiple studies have shown that clones of infected cells are shared between anatomical sites, highlighting their trafficking throughout the body. Newly generated data further confirm a lack of HIV compartmentalization between anatomical sites, suggesting the absence of viral replication in blood and tissues under ART despite previous reports of low antiretroviral penetration in certain tissues. Recent observations also suggest that infected cells belonging to the same clone may display different phenotypes depending on their anatomical location, although direct proof of the plasticity of infected T cell clones is still lacking.</p><p><strong>Summary: </strong>Postmortem studies have identified HIV-infected cells in almost all tissues analyzed, highlighting the importance of studying tissues to gain further insights into HIV persistence and clonality. Sensitive approaches that enable simultaneous analysis of the T-cell receptor and phenotypic traits of HIV-infected clones from matched blood and tissue samples will be key to unravel antigen specificity, as well as the distribution of infected clones across anatomical compartments and their phenotypic plasticity, ultimately facilitating the development of therapeutic strategies.</p>","PeriodicalId":93966,"journal":{"name":"Current opinion in HIV and AIDS","volume":" ","pages":"519-525"},"PeriodicalIF":4.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144983896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Use of implementation theories, models, and frameworks in PrEP implementation research from 2022-2025: innovation and participation.","authors":"Christopher G Kemp","doi":"10.1097/COH.0000000000000978","DOIUrl":"10.1097/COH.0000000000000978","url":null,"abstract":"<p><strong>Purpose of review: </strong>Use of implementation theories, models, and frameworks (TMFs) in HIV research is growing substantially, yet their impact may be limited by superficial application and poor alignment with community needs. This review highlights recent examples of TMF use in pre-exposure prophylaxis (PrEP) implementation studies and discusses how to increase their accessibility and utility for more equitable implementation.</p><p><strong>Recent findings: </strong>Studies from 2022-2025 ( n = 26) demonstrate more sophisticated TMF use, often layering frameworks and integrating participatory approaches and co-creation. Key themes include treating TMFs as boundary objects to facilitate partner dialogue, grounding theory in lived experience, and developing specific program theories.</p><p><strong>Summary: </strong>TMFs can support equitable PrEP implementation when applied flexibly and in partnership with communities. Researchers and practitioners can use TMFs as adaptable tools for dialogue and as the basis for further co-creation. Structured, participatory methods that help co-adapt frameworks and develop context-specific theories of change are crucial for translating assessment into effective, actionable strategies and improving HIV prevention outcomes.</p>","PeriodicalId":93966,"journal":{"name":"Current opinion in HIV and AIDS","volume":" ","pages":"578-586"},"PeriodicalIF":4.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144994825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Integrating socio-behavioral, ethics, community, and translational science considerations in HIV cure research.","authors":"Karine Dubé, Ali Ahmed, John A Sauceda","doi":"10.1097/COH.0000000000000955","DOIUrl":"10.1097/COH.0000000000000955","url":null,"abstract":"<p><strong>Purpose of review: </strong>HIV cure research efforts are expanding globally, yet several critical areas in the socio-behavioral, ethics, community engagement, and translational aspects remain underexplored. This article critically reviews the relevant literature from the past 5 years (2021-2025), highlights key gaps, and offers recommendations for future research.</p><p><strong>Recent findings: </strong>The multidisciplinary literature on HIV cure research is expanding, but urgent attention is required in several areas. These include the integration of socio-behavioral, ethics, and community engagement perspectives into HIV cure trials, with an increased emphasis on translation to resource-limited settings. The intersection of socio-behavioral sciences, ethics, and translational science requires more tailored research to ensure the deployment of socially impactful interventions.</p><p><strong>Summary: </strong>Critical areas for further research include: increased scholarship in socio-behavioral sciences and ethics alongside scientific advancements in HIV cure research; expanding formative research in resource-limited settings and enhancing integration within analytical treatment interruption (ATI)-inclusive trials; continued implementation of the behavioral and social sciences research functional framework and evidence-based approaches into trial designs; strengthening psychosocial support and ethical frameworks for trial participants; and redressing power imbalances between scientific disciplines, ensuring socio-behavioral, ethics and community considerations are central, not secondary, to HIV cure research efforts worldwide.</p>","PeriodicalId":93966,"journal":{"name":"Current opinion in HIV and AIDS","volume":" ","pages":"565-573"},"PeriodicalIF":4.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12431633/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145034801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The female microbiome in HIV prevention, pathogenesis, and treatment.","authors":"Brandilyn A Peters, Mykhaylo Usyk, Robert D Burk","doi":"10.1097/COH.0000000000000986","DOIUrl":"10.1097/COH.0000000000000986","url":null,"abstract":"<p><strong>Purpose of review: </strong>To summarize the relationship of vaginal and gut microbiomes with HIV transmission, pathogenesis, and treatment, focusing on women's health.</p><p><strong>Recent findings: </strong>Bacterial vaginosis (i.e., vaginal microbiome dysbiosis) is a well established risk factor for HIV acquisition, and recent research focused on molecular mechanisms and biomarkers for HIV acquisition related to vaginal microbiota. Recent clinical trials reported on probiotics to treat bacterial vaginosis with the goal of HIV prevention; however, durability of treatment response remains sub-optimal. The vaginal microbiome may impact efficacy of preexposure prophylaxis (PrEP) and antiretroviral therapy (ART) in vaginal tissue, with recent literature examining vaginal microbiota and long-acting PrEP vaginal rings. Some research also suggests effects of PrEP or ART initiation on the vaginal microbiome. Regarding the gut microbiome, associations with HIV status may differ more by sexual practices than biological sex, and sex-specific roles of gut microbiota in HIV pathogenesis and treatment are unknown. Interactions of the gut microbiome with estrogens could underlie a role of gut microbiota in health of women with HIV.</p><p><strong>Summary: </strong>The vaginal microbiome remains an important factor in HIV acquisition, prevention, and treatment in women. The gut microbiome has roles in HIV pathogenesis and treatment, but women-specific effects are unclear.</p>","PeriodicalId":93966,"journal":{"name":"Current opinion in HIV and AIDS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145305014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Prospects for therapeutic T-cell vaccine strategies for HIV cure.","authors":"Beatriz Mothe, Christian Brander","doi":"10.1097/COH.0000000000000965","DOIUrl":"10.1097/COH.0000000000000965","url":null,"abstract":"<p><strong>Purpose of review: </strong>This review article aims to summaries the advances in T-cell vaccination as a component of HIV cure strategies. Recent clinical trials of therapeutic vaccination showing small but intriguing efficacy signals, provide the field with the data necessary to embark on informed combination strategies that build on these advances. The review focusses on aspects of T-cell immunogen design and vector use for vaccination, and discusses the effects of adjuvants and combination strategies on vaccine-induced immunity and their impact on virus control in people with HIV who undergo an analytical treatment interruption.</p><p><strong>Recent findings: </strong>Vaccine-induced virus-specific T-cell immunity has been linked to relative control of viral replication in several recent clinical trials. Different immunogen concepts have also entered clinical trials, but for only a few are there immunogenicity and efficacy data available. New initiatives that leverage innate immune mechanisms show some interesting prospect to improve antiviral immunity. The available data also indicate that the preexisting T-cell immunity plays an important role in the strength and breadth of the vaccine-induced immunity.</p><p><strong>Summary: </strong>With some efficacy data supporting the role of antiviral T-cell immunity, strategies that improve this response further can be delineated and incorporated into future, more potent combination approaches.</p>","PeriodicalId":93966,"journal":{"name":"Current opinion in HIV and AIDS","volume":" ","pages":"463-471"},"PeriodicalIF":4.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12337920/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144602627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pavitra Ramdas, Ramón A Lujan, Prakriti Mudvari, Liliana Pérez, Eli A Boritz
{"title":"Single cell technologies and the biology of HIV-infected CD4 T-cell reservoirs.","authors":"Pavitra Ramdas, Ramón A Lujan, Prakriti Mudvari, Liliana Pérez, Eli A Boritz","doi":"10.1097/COH.0000000000000968","DOIUrl":"10.1097/COH.0000000000000968","url":null,"abstract":"<p><strong>Purpose of review: </strong>Although populations of rare HIV-infected CD4 T cells that persist under antiretroviral therapy (ART) are believed to be a major barrier to HIV cure, technical obstacles have made it impossible to determine whether these cells possess distinctive attributes that enable their persistence. Here we review the development of technologies that have begun to allow HIV-infected cells in their natural state to be described comprehensively.</p><p><strong>Recent findings: </strong>As widely used platforms that analyze single-cells within water-in-oil droplets have yielded information about HIV-infected CD4 T cells ex vivo, adaptations of these platforms and custom workflows that address additional technical obstacles specific to some HIV-infected cells have also been developed. These advancements, combined with analyses of defined participant cohorts, tissue-derived cells, and unique clinical scenarios, have provided mounting evidence that HIV-infected cells under ART have distinctive host transcriptomic and epigenetic profiles that may help explain their persistence in vivo.</p><p><strong>Summary: </strong>Single-cell analytical technologies that can comprehensively describe the biology of HIV-infected cells under ART promise new discoveries that may accelerate development of safe and scalable HIV cure strategies.</p>","PeriodicalId":93966,"journal":{"name":"Current opinion in HIV and AIDS","volume":"20 5","pages":"474-480"},"PeriodicalIF":4.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12333547/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144796482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Advancing HIV cure: insights from developing chronic hepatitis b therapies for functional cure.","authors":"Ana Verma, Raymond T Chung","doi":"10.1097/COH.0000000000000956","DOIUrl":"https://doi.org/10.1097/COH.0000000000000956","url":null,"abstract":"<p><strong>Purpose of review: </strong>Similarly to HIV, HBV assumes a highly stable nuclear form and becomes integrated into the host genome, posing a significant challenge to complete eradication. The purpose of this review is to highlight the recent progress on various therapies that are being explored to achieve functional cure (FC) of chronic Hepatitis B (CHB).</p><p><strong>Recent findings: </strong>The current standard-of-care for CHB is either nucleos(t)ide analogues (NA) or PegIFN-α, but neither alone is sufficient to achieve functional cure. However, NA cessation alone or followed by PegIFN-α shows promise for increasing functional cure rates and decreasing viral relapse rates. While first generation capsid-assembly modulators (CAMs) had virtually no impact on HBsAg, newer, more potent CAMs may have an effect on cccDNA and produce reductions in HBsAg levels. Small-interfering RNAs (siRNAs) can lower HBsAg, but do not appear to result in sustained HBsAg clearance. A similar agent, bepirovirsen (an antisense oligonucleotide), appears to be more effective in producing modest FC rates; this may be due to its possible induction of the innate immune response.</p><p><strong>Summary: </strong>Given the persistence of cccDNA and integrated DNA, together with HBsAg-induced immune dysfunction, successful treatment for CHB to induce FC is likely to require a combination of agents that inhibit viral replication, reduce HBsAg levels, and boost the antiviral immune response.</p>","PeriodicalId":93966,"journal":{"name":"Current opinion in HIV and AIDS","volume":"20 5","pages":"449-455"},"PeriodicalIF":4.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144796481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Single-cell sequencing technologies: a multiomics toolbox for investigating HIV-1 persistence.","authors":"Alberto Bosque, Rasmi Thomas","doi":"10.1097/COH.0000000000000966","DOIUrl":"https://doi.org/10.1097/COH.0000000000000966","url":null,"abstract":"","PeriodicalId":93966,"journal":{"name":"Current opinion in HIV and AIDS","volume":"20 5","pages":"472-473"},"PeriodicalIF":4.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144796483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Roadmap for spatial transcriptomics of HIV in tissues.","authors":"Qijie Guan, Amare Eshetu, Ya-Chi Ho","doi":"10.1097/COH.0000000000000961","DOIUrl":"10.1097/COH.0000000000000961","url":null,"abstract":"<p><strong>Purpose of review: </strong>Mechanisms of HIV persistence in tissues are distinct from that in the blood. Spatial transcriptomic profiling examines HIV-infected cells, surrounding neighborhoods, and tissue microenvironment in unprecedented resolution. Spatial profiling captures cytokine gradients, distances between HIV-infected cells and immune effectors (and their function versus exhaustion), and cell-cell interactions. We present an overview of spatial transcriptomic platforms and a workflow of quality controls, sanity check, and bioinformatic analysis.</p><p><strong>Recent findings: </strong>The selection of spatial profiling methods should base on the research question, resolution, breadth of coverage, the expression level of RNA of interest, tissue quality, and tissue size. Advanced spatial transcriptomic profiling can capture RNA molecules at high resolution (<1 μm) and thus enable near-single cell profiling at genome-wide (~20 000 genes) breadth. Specifically, poly-A-based mRNA capture can identify previously unknown targets, while targeted RNA capture increases sensitivity in low-quality tissues. In targeted capture, however, the increase in target numbers frequently decreases sensitivity. Coupling ATAC-seq, protein capture, and T cell receptor sequencing to spatial platforms is ongoing.</p><p><strong>Summary: </strong>Spatial transcriptomic profiling uncovers mechanisms of HIV persistence in tissues and informs therapeutic strategies. Investigators should ensure the rigor of analysis, validate findings, and avoid reporting signatures with unknown biological significance.</p>","PeriodicalId":93966,"journal":{"name":"Current opinion in HIV and AIDS","volume":" ","pages":"502-511"},"PeriodicalIF":4.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144585952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}