Current opinion in HIV and AIDS最新文献

{"title":"Type I, N332-glycan-dependent and Type II, N332-glycan-independent V3-glycan antibodies against HIV-1.","authors":"Ignacio Relano-Rodriguez, Amelia Escolano","doi":"10.1097/COH.0000000000001063","DOIUrl":"10.1097/COH.0000000000001063","url":null,"abstract":"<p><strong>Purpose of review: </strong>The V3-glycan supersite is a recurrent target of HIV-1 broadly neutralizing antibodies (bNAbs) and a major focus of vaccine and therapeutic development. Classical V3-glycan bNAbs engage the epitope through contacts with the glycan at position N332 of the HIV envelope. This review summarizes new findings demonstrating that V3-glycan epitope recognition is not restricted to N332-glycan-dependent antibodies and provides clarification about the new classification of V3-glycan antibodies.</p><p><strong>Recent findings: </strong>A new class of N332-glycan-independent V3-glycan antibodies has been identified. Two new human bNAbs, EPTC112 and 007, target the V3-glycan epitope in an N332-glycan-independent manner and exhibit complementary neutralization activity to classical N332-glycan-dependent bNAbs. In addition, WIN332, the first immunogen rationally designed to elicit N332-glycan-independent V3-glycan antibodies, has induced this antibody class in macaques. These findings have prompted the proposal of a revised classification and nomenclature for V3-glycan antibodies, in which canonical N332-glycan-dependent antibodies are designated as Type I, whereas the newly identified N332-glycan-independent antibodies are designated as Type II.</p><p><strong>Summary: </strong>The identification of Type II V3-glycan bNAbs demonstrates that broad neutralization can be achieved through previously unrecognized modes of Env recognition. Coupled with the ability of WIN332 to induce this antibody class, these findings expand the landscape for antibody discovery, therapeutic development, and vaccine design.</p>","PeriodicalId":93966,"journal":{"name":"Current opinion in HIV and AIDS","volume":" ","pages":"426-432"},"PeriodicalIF":4.0,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148835711","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":"Induction of HIV broadly neutralizing antibodies with vaccination in humans in discovery medicine trials.","authors":"Barton F Haynes, Chen-Hao Yeh, Lindsey R Baden","doi":"10.1097/COH.0000000000001070","DOIUrl":"10.1097/COH.0000000000001070","url":null,"abstract":"<p><strong>Purpose of review: </strong>Since our last review of progress in inducing HIV broadly neutralizing antibodies (bnAbs) in 2023, advances have been made in achieving bnAb induction in humans. The purpose of this review is to discuss this progress and to outline remaining tasks needed to complete a prototype HIV vaccine.</p><p><strong>Recent findings: </strong>Several published clinical trials have succeeded in inducing bnAb precursors of multiple types, including membrane proximal external region (MPER), CD4 + -mimicking CD4 + -binding site (bs) and HCDR3-dominant CD4bs. Trials are underway or nearing completion for inducing V2-apex and V3-glycan bnAb precursors.</p><p><strong>Summary: </strong>Progress is being made in developing vaccine immunogens that induce bnAb B cell lineages in humans. The next tasks are to design boosting immunogens that complete bnAb affinity maturation, and to do so for two to three different bnAb specificities to prevent transmitted-founder virus escape during HIV transmission. A final task is to utilize a vaccine platform that will induce high-tittered, durable serum bnAb activity capable of providing protection for multiple years.</p>","PeriodicalId":93966,"journal":{"name":"Current opinion in HIV and AIDS","volume":" ","pages":"442-449"},"PeriodicalIF":4.0,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148972722","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":"Weight gain, adipose tissue remodeling and cardiometabolic disease in people with HIV.","authors":"Jennifer Gorwood, Jacqueline Capeau, Véronique Béréziat, Claire Lagathu","doi":"10.1097/COH.0000000000001069","DOIUrl":"10.1097/COH.0000000000001069","url":null,"abstract":"<p><strong>Purpose of review: </strong>Weight gain and associated adipose tissue remodeling have been partly linked to HIV infection and to some current antiretroviral therapy (ART) regimens in ART-naive and ART-controlled people with HIV (PWH). This review addresses recent findings on adipose tissue distribution and remodeling in PWH, receiving dolutegravir, bictegravir and/or tenofovir alafenamide (TAF), highlighting how visceral adiposity contributes to cardiometabolic comorbidities.</p><p><strong>Recent findings: </strong>Preclinical models exposed to dolutegravir, bictegravir, tenofovir disoproxil fumarate (TDF) and/or TAF demonstrate alterations in adipose tissue, including mitochondrial dysfunction, fibrosis, inhibited beiging, and insulin resistance. Transcriptomic studies of abdominal subcutaneous fat from ART-controlled PWH further revealed elevated inflammation, fibrosis and insulin resistance. Increased visceral adiposity raises the risk of cardiometabolic disorders such as insulin resistance and diabetes, metabolic-dysfunction-associated steatotic liver disease and cardiovascular diseases. Reversing weight gain linked to ART, by switching regimens or adding antiobesity medications like the GLP-1 receptor agonist semaglutide, has shown potential in reducing adipose tissue remodeling, visceral adiposity and cardiometabolic risk factors.</p><p><strong>Summary: </strong>Weight gain and increased visceral adiposity partly driven by some ARTs are associated with higher cardiometabolic risk. HIV and ART can either activate or suppress the fat beiging/browning phenotype. Reversing weight gain and visceral adiposity in at-risk PWH is a critical clinical goal.</p>","PeriodicalId":93966,"journal":{"name":"Current opinion in HIV and AIDS","volume":"21 6","pages":"480-487"},"PeriodicalIF":4.0,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149120516","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":"Fundamental B-cell biology factors impacting HIV vaccine development.","authors":"Kristy M Waldrep, Mauricio V Padilla, Robert K Abbott","doi":"10.1097/COH.0000000000001071","DOIUrl":"10.1097/COH.0000000000001071","url":null,"abstract":"<p><strong>Purpose of review: </strong>To cover recent work on fundamental immunological mechanisms and strategies to elicit successful priming and boosting of B cells in HIV vaccine efforts.</p><p><strong>Recent findings: </strong>HIV vaccine research has reached substantial milestones in recent years, showing successful priming and early boosting of desired precursor B cells in humans - the first steps toward an effective HIV vaccine. Moreover, recent studies have started to unravel key vaccine strategies that are important for both sequential immunization and eliciting durable vaccine responses, including immunogen engineering, novel adjuvants, extended antigen dosing regimens, booster timing, and modulating antigen avidity.</p><p><strong>Summary: </strong>A successful HIV vaccine will likely require elicitation of broadly neutralizing antibodies (bnAbs) and sustainment of sufficient serum bnAb titers. At the cellular level, induction of effective germinal center reactions, as well as sufficient bnAb-secreting long-lived plasma cells (LLPC) in the final boost, will likely be required.</p>","PeriodicalId":93966,"journal":{"name":"Current opinion in HIV and AIDS","volume":" ","pages":"416-425"},"PeriodicalIF":4.0,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148972789","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":"Weight gain in people with HIV in Africa and Asia: a review of causes, consequences, and management implications.","authors":"Willem Daniel Francois Venter, Simiso Mandisa Sokhela, Jen Manne-Goehler","doi":"10.1097/COH.0000000000001074","DOIUrl":"10.1097/COH.0000000000001074","url":null,"abstract":"<p><strong>Purpose of review: </strong>To examine weight gain epidemiology in people with HIV (PLWH) across Africa and Asia, focusing on data published in the preceding 18 months, and to identify clinical and programmatic implications, acknowledging that regionally derived evidence remains sparse.</p><p><strong>Recent findings: </strong>New population-level data from East Africa demonstrate that the nutrition transition is accelerating faster than ART-related weight gain. Thus, HIV-negative individuals gained more weight than PLWH on ART over the transition to dolutegravir regimens in rural Kenya and Uganda. In Asian cohorts, men gained more weight than women after ART initiation. This is the reverse of the sex-specific changes in body weight seen in Africa, and this is particularly worrisome because standard BMI thresholds systematically underestimate cardiometabolic risk in this population. Programmatic data from Uganda have shown that dolutegravir exposure doubles the risk of incident hypertension even after adjustment for BMI change. ART switch trials conducted in high-income settings (DEFINE, ACTG A5391) confirm that regimen changes do not reverse established obesity; however, emerging data from a South African randomized trial (Opti-DOR) suggest that regimen at ART initiation influences weight trajectory. GLP-1 therapies demonstrate compelling efficacy for both weight loss and cardiometabolic health improvement in PLWH, including in Africa, but remain economically inaccessible.</p><p><strong>Summary: </strong>Weight gain in people with HIV in Africa and Asia reflects the convergence of the nutrition transition, ART pharmacology, and immune reconstitution, disproportionately affecting women in African cohorts and men in Asian cohorts. Cardiometabolic consequences, particularly hypertension, are now robustly documented in African programmatic data, but equivalent evidence from Asia remains sparse. Switching ART does not reverse established obesity, although regimen choice at initiation influences weight trajectory. Access to antiobesity medications may be the defining health policy challenge for these populations over the next decade.</p>","PeriodicalId":93966,"journal":{"name":"Current opinion in HIV and AIDS","volume":"21 6","pages":"460-466"},"PeriodicalIF":4.0,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149120527","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":"Zooming in on T-cell protection.","authors":"Tomáš Hanke","doi":"10.1097/COH.0000000000001062","DOIUrl":"10.1097/COH.0000000000001062","url":null,"abstract":"<p><strong>Purpose of review: </strong>This review aims to deepen our appreciation of the intricate interactions underpinning CD8 + T-cell-mediated immunity to HIV-1, from the whole-cell level to the structure and function of signalling molecules driving diverse transcriptional programmes and differentiation states.</p><p><strong>Recent findings: </strong>Unravelling the signals that trigger T-cell activation, elucidating the dynamic architecture of the immunological synapse, and comprehensive, high-resolution tissue cell atlases are transforming our understanding of T-cell biology during viral infections.</p><p><strong>Summary: </strong>This review links multiple processes that together generate T-cell immunity with possible implications for vaccine development. It begins by examining the role of T-cell-mediated responses in protection against HIV-1 and the importance of targeting vulnerable epitopes on HIV-1 proteins to suppress viral replication. It then zooms in on the initiation of T-cell activation, differentiation, and effector functions, mediated by the formation of the immunological synapse, co-stimulatory signalling, and cytokine networks, which drive coordinated actions of multiple transcription factors and chromatin remodelling. It emphasizes the importance of T-cell diversity, the continuum of cellular differentiation states, tissue localization, and memory formation in shaping effective antiviral immunity.</p>","PeriodicalId":93966,"journal":{"name":"Current opinion in HIV and AIDS","volume":" ","pages":"403-409"},"PeriodicalIF":4.0,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148803406","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":"Preclinical and clinical trials for vaccine induction of CD4-binding site neutralizing antibodies.","authors":"Catarina Mendes Silva, Rogier W Sanders, Tom G Caniels","doi":"10.1097/COH.0000000000001065","DOIUrl":"10.1097/COH.0000000000001065","url":null,"abstract":"<p><strong>Purpose of review: </strong>To summarize current preclinical and clinical efforts to induce CD4bs-directed broadly neutralizing antibodies (bnAbs) against HIV-1 Env using germline-targeting and lineage-based vaccination strategies, and to highlight how differences in immunogen design, particularly along gradients of precursor affinity and structural constraint, shape VRC01-class responses and inform subsequent shaping and polishing steps in vaccine regimens.</p><p><strong>Recent findings: </strong>Phase 1 trials of CD4bs-directed germline-targeting immunogens have shown that VRC01-class precursors can be reproducibly expanded in humans. Smaller gp120-based immunogens exhibit higher precursor affinity and recruit larger, more diverse VRC01-class pools, whereas native-like trimers prime fewer lineages but drive more on-track somatic hypermutation, early glycan accommodation, and neutralization of heterologous viruses. In parallel, preclinical work is centred around the selection of shaping and polishing immunogens, alternative dosing strategies, and controlled-release or mRNA-LNP platforms to extend maturation.</p><p><strong>Summary: </strong>With proof-of-concept for VRC01-class priming being achieved, the next challenge is to induce strong serum antibodies and memory B cells with breadth and potency. Progress toward a protective CD4bs-directed HIV-1 vaccine will require further optimization of adjuvants, delivery systems, and sequential immunogen design to balance precursor recruitment with structural constraint and to sustain affinity maturation across multidose regimens, ultimately driving rare lineages to durable bnAb responses in diverse populations.</p>","PeriodicalId":93966,"journal":{"name":"Current opinion in HIV and AIDS","volume":" ","pages":"433-441"},"PeriodicalIF":4.0,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148814524","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":"Development of adjuvanted HIV vaccines tailored for early life: immunologic rationale, clinical experience, and future directions.","authors":"Kinga K Smolen, Kristina De Paris, Asimenia Angelidou, Troy M Martin, Simon D van Haren, Ofer Levy","doi":"10.1097/COH.0000000000001068","DOIUrl":"10.1097/COH.0000000000001068","url":null,"abstract":"<p><strong>Purpose of review: </strong>This review highlights the rationale for and clinical experience in advancing age-specific adjuvantation systems to develop well tolerated and effective pediatric HIV vaccines.</p><p><strong>Recent findings: </strong>Due to both cellular and soluble factors, infant immunity is distinct from that of older children and adults, featuring Th2 bias, tolerogenic APC programming, and reduced Tfh support. Due to distinct functional responses downstream of pattern recognition receptor signaling, adjuvant action is age-specific. Despite a growing pipeline of adjuvants and increasing interest in developing early-life immunization strategies against HIV, few adjuvants have been rigorously evaluated for use in pediatric HIV vaccines. In line with FDA Modernization Act 2.0, systems vaccinology and age-specific immunoprofiling in vivo and in vitro can inform down selection and optimization of age-specific adjuvanted HIV vaccine formulations. Several adjuvants have been assessed as components of HIV vaccines in infants including Alum, the oil-in-water emulsion MF59 and the TLR4 agonist glucopyranosyl lipid A (GLA).</p><p><strong>Summary: </strong>There is strong rationale to develop an infant HIV vaccine to provide early-life protection, and several adjuvants have been assessed thus far in early-phase clinical studies. With a growing adjuvant pipeline, much work remains to assess which adjuvants should be advanced for an infant HIV vaccine. Leveraging age-specific preclinical studies including immune profiling and human in-vitro modeling can inform down selection to identify adjuvantation systems offering safety and antigen dose sparing, while enhancing breadth and durability of vaccine immunogenicity.</p>","PeriodicalId":93966,"journal":{"name":"Current opinion in HIV and AIDS","volume":" ","pages":"488-498"},"PeriodicalIF":4.0,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148876867","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":"The next frontier: AI, multi-omics, and predictive models for weight gain in HIV.","authors":"Samuel S Bailin","doi":"10.1097/COH.0000000000001061","DOIUrl":"10.1097/COH.0000000000001061","url":null,"abstract":"<p><strong>Purpose of review: </strong>People with HIV (PWH) are increasingly susceptible to excess weight gain and obesity after initiation of antiretroviral therapy. However, there is substantial variation in individual weight gain that is difficult to predict with clinical factors alone. We review emerging methods in machine learning and multi-omics that address the biology and prediction of weight gain and weight-associated conditions, persistent challenges, and future directions.</p><p><strong>Recent findings: </strong>PWH continue to have increasing burden of excess weight gain and obesity. Obesity has a complex pathophysiology with an interplay between biological and environmental factors that make weight gain prediction challenging. Few studies in PWH have used omics or machine learning to capture weight gain trajectories. These studies highlight the promise and challenges of leveraging multi-omics and machine learning for modeling weight gain.</p><p><strong>Summary: </strong>Advances in machine learning and scalable multi-omics have accelerated research defining pathways of human health and disease. These tools may have an important role in defining the biology and predictors of weight gain in PWH, ultimately to improve risk stratification and identify targeted interventions to improve health outcomes in PWH.</p>","PeriodicalId":93966,"journal":{"name":"Current opinion in HIV and AIDS","volume":" ","pages":"467-472"},"PeriodicalIF":4.0,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148724823","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":"Recent insights from prophylactic passive immunization trials of HIV-1 broadly neutralizing antibodies: implications for vaccine design.","authors":"Penny L Moore","doi":"10.1097/COH.0000000000001064","DOIUrl":"10.1097/COH.0000000000001064","url":null,"abstract":"<p><strong>Purpose of review: </strong>An HIV-1 vaccine remains an urgent need, underscored by funding cuts that threaten treatment programs. The antibody mediated prevention (AMP) trials confirmed that broadly neutralizing antibodies (bNAbs) can prevent HIV-1 acquisition, and provided paradigm-shifting insights into HIV-1 biology and protective thresholds. This review discusses the implications of these findings for HIV-1 vaccine design and identifies some of the key knowledge gaps that remain.</p><p><strong>Recent findings: </strong>The AMP trials emphasized the necessity of potent, broad bNAbs to prevent HIV-1 acquisition. Subsequent pharmacokinetic and neutralization analyses defined quantitative thresholds of protection, essential for benchmarking future success. However, questions remain regarding the extrapolation of VRC01-derived PT80 to other bNAbs and modes of transmission. Deep envelope sequencing from the AMP trials has revised our understanding of the transmission bottleneck, by revealing frequent multilineage infections and co-transmission of viruses with different sensitivities to VRC01. These factors challenge prevention and favour rapid escape under antibody pressure.</p><p><strong>Summary: </strong>These studies have provided essential immunological and virological insights relevant to HIV-1 vaccine design, and have refined our understanding of protective thresholds and early viral events. Together, these findings emphasize the need for combinations of potent, broad antibodies and better define the barriers to HIV-1 vaccine design.</p>","PeriodicalId":93966,"journal":{"name":"Current opinion in HIV and AIDS","volume":"21 6","pages":"410-415"},"PeriodicalIF":4.0,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149120608","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}