Current opinion in HIV and AIDS最新文献

{"title":"Untangling the role of the microbiome across the stages of HIV disease.","authors":"Alexandra M Ortiz, Jason M Brenchley","doi":"10.1097/COH.0000000000000870","DOIUrl":"10.1097/COH.0000000000000870","url":null,"abstract":"<p><strong>Purpose of review: </strong>The primate microbiome consists of bacteria, eukaryotes, and viruses that dynamically shape and respond to host health and disease. Understanding how the symbiotic relationship between the host and microbiome responds to HIV has implications for therapeutic design.</p><p><strong>Recent findings: </strong>Advances in microbiome identification technologies have expanded our ability to identify constituents of the microbiome and to infer their functional capacity. The dual use of these technologies and animal models has allowed interrogation into the role of the microbiome in lentiviral acquisition, vaccine efficacy, and the response to antiretrovirals. Lessons learned from such studies are now being harnessed to design microbiome-based interventions.</p><p><strong>Summary: </strong>Previous studies considering the role of the microbiome in people living with HIV largely described viral acquisition as an intrusion on the host:microbiome interface. Re-framing this view to consider HIV as a novel, albeit unwelcome, component of the microbiome may better inform the research and development of pre and postexposure prophylaxes.</p>","PeriodicalId":93966,"journal":{"name":"Current opinion in HIV and AIDS","volume":" ","pages":"221-227"},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11305932/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141461344","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":"Neuroinflammation and mental health outcomes in adolescents living with HIV","authors":"Arish Mudra Rakshasa-Loots, Jaime H. Vera, Barbara Laughton","doi":"10.1097/coh.0000000000000877","DOIUrl":"https://doi.org/10.1097/coh.0000000000000877","url":null,"abstract":"\u0000 \u0000 Adolescents living with HIV show chronic inflammation, which in turn has been linked to mental health outcomes in the general population. The increased risk for mental health issues in adolescents with HIV may thus be driven by HIV-related inflammation. In this review, we discuss the associations between peripheral and central nervous system inflammation and mental health outcomes in adolescents with HIV.\u0000 \u0000 \u0000 \u0000 Preclinical models indicate that expression of HIV viral proteins early in life may lead to neuroinflammation and behavioural deficits in adolescence. Clinical evidence is available primarily in the general population and in adults with HIV, and suggests that inflammatory biomarkers such as IL-6 and TNF-α may be associated with depressive symptoms. Only one study has explored these relationships in adolescents with HIV, and did not find that inflammatory biomarkers in the blood or brain were linked to depressive symptoms. Current research in this field focuses overwhelmingly on peripheral inflammatory biomarkers (compared to neuroimaging biomarkers) and on depression (compared to other mental health conditions).\u0000 \u0000 \u0000 \u0000 There is strong evidence to suggest that neuroinflammation and peripheral inflammation may play a role in the development of mental health issues in adolescents, but research in adolescents with HIV is sparse. Characterizing the relationship between inflammation and mental health in adolescents with HIV may help improve the prediction, prevention, early intervention, and treatment of mental health issues in this population.\u0000","PeriodicalId":93966,"journal":{"name":"Current opinion in HIV and AIDS","volume":"46 s157","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141834804","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":"Gaining momentum: stem cell therapies for HIV cure.","authors":"Amanda M Buck, Brian H LaFranchi, Timothy J Henrich","doi":"10.1097/COH.0000000000000859","DOIUrl":"10.1097/COH.0000000000000859","url":null,"abstract":"<p><strong>Purpose of review: </strong>Durable HIV-1 remission has been reported in a person who received allogeneic stem cell transplants (SCTs) involving CCR5 Δ32/Δ32 donor cells. Much of the reduction in HIV-1 burden following allogeneic SCT with or without donor cells inherently resistant to HIV-1 infection is likely due to cytotoxic graft-versus-host effects on residual recipient immune cells. Nonetheless, there has been growing momentum to develop and implement stem cell therapies that lead to durable long-term antiretroviral therapy (ART)-free remission without the need for SCT.</p><p><strong>Recent findings: </strong>Most current research leverages gene editing techniques to modify hematopoietic stem cells which differentiate into immune cells capable of harboring HIV-1. Approaches include targeting genes that encode HIV-1 co-receptors using Zinc Finger Nucleases (ZFN) or CRISPR-Cas-9 to render a pool of adult or progenitor cells resistant to de-novo infection. Other strategies involve harnessing multipotent mesenchymal stromal cells to foster immune environments that can more efficiently recognize and target HIV-1 while promoting tissue homeostasis.</p><p><strong>Summary: </strong>Many of these strategies are currently in a state of infancy or adolescence; nonetheless, promising preclinical and first-in-human studies have been performed, providing further rationale to focus resources on stem cell therapies.</p>","PeriodicalId":93966,"journal":{"name":"Current opinion in HIV and AIDS","volume":" ","pages":"194-200"},"PeriodicalIF":0.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11155292/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140875013","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":"Immune checkpoint inhibition as a therapeutic strategy for HIV eradication: current insights and future directions.","authors":"Jina Lee, James B Whitney","doi":"10.1097/COH.0000000000000863","DOIUrl":"10.1097/COH.0000000000000863","url":null,"abstract":"<p><strong>Purpose of review: </strong>HIV-1 infection contributes substantially to global morbidity and mortality, with no immediate promise of an effective prophylactic vaccine. Combination antiretroviral therapy (ART) suppresses HIV replication, but latent viral reservoirs allow the virus to persist and reignite active replication if ART is discontinued. Moreover, inflammation and immune disfunction persist despite ART-mediated suppression of HIV. Immune checkpoint molecules facilitate immune dysregulation and viral persistence. However, their therapeutic modulation may offer an avenue to enhance viral immune control for patients living with HIV-1 (PLWH).</p><p><strong>Recent findings: </strong>The success of immune checkpoint inhibitor (ICI) therapy in oncology suggests that targeting these same immune pathways might be an effective therapeutic approach for treating PLWH. Several ICIs have been evaluated for their ability to reinvigorate exhausted T cells, and possibly reverse HIV latency, in both preclinical and clinical HIV-1 studies.</p><p><strong>Summary: </strong>Although there are very encouraging findings showing enhanced CD8 + T-cell function with ICI therapy in HIV infection, it remains uncertain whether ICIs alone could demonstrably impact the HIV reservoir. Moreover, safety concerns and significant clinical adverse events present a hurdle to the development of ICI approaches. This review provides an update on the current knowledge regarding the development of ICIs for the remission of HIV-1 in PWH. We detail recent findings from simian immunodeficiency virus (SIV)-infected rhesus macaque models, clinical trials in PLWH, and the role of soluble immune checkpoint molecules in HIV pathogenesis.</p>","PeriodicalId":93966,"journal":{"name":"Current opinion in HIV and AIDS","volume":" ","pages":"179-186"},"PeriodicalIF":0.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140924089","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":"Editorial introduction.","authors":"","doi":"10.1097/COH.0000000000000862","DOIUrl":"https://doi.org/10.1097/COH.0000000000000862","url":null,"abstract":"","PeriodicalId":93966,"journal":{"name":"Current opinion in HIV and AIDS","volume":"19 4","pages":"v"},"PeriodicalIF":0.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141263533","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":"A behavioral economics approach to enhancing HIV preexposure and postexposure prophylaxis implementation.","authors":"Jingjing Li, Yaxin Liu, Eric Nehl, Joseph D Tucker","doi":"10.1097/COH.0000000000000860","DOIUrl":"10.1097/COH.0000000000000860","url":null,"abstract":"<p><strong>Purpose of review: </strong>The 'PrEP cliff' phenomenon poses a critical challenge in global HIV PrEP implementation, marked by significant dropouts across the entire PrEP care continuum. This article reviews new strategies to address 'PrEP cliff'.</p><p><strong>Recent findings: </strong>Canadian clinicians have developed a service delivery model that offers presumptive PEP to patients in need and transits eligible PEP users to PrEP. Early findings are promising. This service model not only establishes a safety net for those who were not protected by PrEP, but it also leverages the immediate salience and perceived benefits of PEP as a natural nudge towards PrEP use. Aligning with Behavioral Economics, specifically the Salience Theory, this strategy holds potential in tackling PrEP implementation challenges.</p><p><strong>Summary: </strong>A natural pathway between PEP and PrEP has been widely observed. The Canadian service model exemplifies an innovative strategy that leverages this organic pathway and enhances the utility of both PEP and PrEP services. We offer theoretical insights into the reasons behind these PEP-PrEP transitions and evolve the Canadian model into a cohesive framework for implementation.</p>","PeriodicalId":93966,"journal":{"name":"Current opinion in HIV and AIDS","volume":" ","pages":"212-220"},"PeriodicalIF":0.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140871720","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":"Utilizing immunotherapy towards achieving a functional cure for HIV-1.","authors":"Fabrícia Heloisa Cavicchioli Sugiyama, Lisa Loksø Dietz, Ole Schmeltz Søgaard","doi":"10.1097/COH.0000000000000856","DOIUrl":"10.1097/COH.0000000000000856","url":null,"abstract":"<p><strong>Purpose of review: </strong>Advancements in antiretroviral therapy (ART) have positively impacted the life expectancy and possibility of living a normal life for people with HIV-1. However, lifelong daily medication is necessary to prevent disease progression. To this end, immunotherapeutic strategies are being tested with the aim of developing a functional cure in which the immune system effectively controls HIV-1 in the absence of ART.</p><p><strong>Recent findings: </strong>The most promising advances in achieving sustained HIV-1 remission or cure include broadly neutralizing antibodies (bNAbs) that are administered alone or in combination with other agents. Newer and more innovative approaches redirecting T cells or natural killer cells to kill HIV-1 infected cells have also shown promising results. Finally, multiple ongoing trials focus on combining bNAbs with other immune-directed therapies to enhance both innate and adaptive immunity.</p><p><strong>Summary: </strong>While immunotherapies as an alternative to conventional ART have generally proven to be well tolerated, these therapeutic approaches have largely been unsuccessful in inducing ART-free control of HIV-1. However, promising results from recent trials involving bNAbs that have reported durable HIV-1 control among a subset of participants, provide reason for cautious optimism that we with further optimization of these treatment strategies may be able to achieve functional cure for HIV-1.</p>","PeriodicalId":93966,"journal":{"name":"Current opinion in HIV and AIDS","volume":" ","pages":"187-193"},"PeriodicalIF":0.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140856324","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 advances on anti-HIV chimeric antigen receptor-T-cell treatment to provide sustained HIV remission.","authors":"Hang Su, April Mueller, Harris Goldstein","doi":"10.1097/COH.0000000000000858","DOIUrl":"10.1097/COH.0000000000000858","url":null,"abstract":"<p><strong>Purpose of review: </strong>Successful sustained remission of HIV infection has been achieved after CCR5Δ32/Δ32 allogeneic hematopoietic stem cell transplantation for treatment of leukemia in a small cohort of people living with HIV (PLWH). This breakthrough demonstrated that the goal of curing HIV was achievable. However, the high morbidity and mortality associated with bone marrow transplantation limits the routine application of this approach and provides a strong rationale for pursuing alternative strategies for sustained long-term antiretroviral therapy (ART)-free HIV remission. Notably, long-term immune-mediated control of HIV replication observed in elite controllers and posttreatment controllers suggests that potent HIV-specific immune responses could provide sustained ART-free remission in PLWH. The capacity of chimeric antigen receptor (CAR)-T cells engineered to target malignant cells to induce remission and cure in cancer patients made this an attractive approach to provide PLWH with a potent HIV-specific immune response. Here, we review the recent advances in the design and application of anti-HIV CAR-T-cell therapy to provide a functional HIV cure.</p><p><strong>Recent findings: </strong>HIV reservoirs are established days after infection and persist through clonal expansion of infected cells. The continuous interaction between latently infected cells and the immune system shapes the landscape of HIV latency and likely contributes to ART-free viral control in elite controllers. CAR-T cells can exhibit superior antiviral activity as compared with native HIV-specific T cells, particularly because they can be engineered to have multiple HIV specificities, resistance to HIV infection, dual costimulatory signaling, immune checkpoint inhibitors, stem cell derivation, CMV TCR coexpression, and tissue homing ligands. These modifications can significantly improve the capacities of anti-HIV CAR-T cells to prevent viral escape, resist HIV infection, and enhance cytotoxicity, persistence, and tissue penetration. Collectively, these novel modifications of anti-HIV CAR-T cell design have increased their capacity to control HIV infection.</p><p><strong>Summary: </strong>Anti-HIV CAR-T cells can be engineered to provide potent and sustained in-vitro and in-vivo antiviral function. The combination of anti-HIV CAR-T cells with other immunotherapeutics may contribute to long-term HIV remission in PLWH.</p>","PeriodicalId":93966,"journal":{"name":"Current opinion in HIV and AIDS","volume":" ","pages":"169-178"},"PeriodicalIF":0.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140874087","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":"Humanized mice for studying HIV latency and potentially its eradication.","authors":"Moa F Hasler, Roberto F Speck, Nicole P Kadzioch","doi":"10.1097/COH.0000000000000855","DOIUrl":"10.1097/COH.0000000000000855","url":null,"abstract":"<p><strong>Purpose of the review: </strong>The quest for an HIV cure faces a formidable challenge: the persistent presence of latent viral infections within the cells and tissues of infected individuals. This review provides a thorough examination of discussions surrounding HIV latency, the use of humanized mouse models, and strategies aimed at eliminating the latent HIV reservoir. It explores the hurdles and advancements in understanding HIV pathogenesis, mainly focusing on establishing latent reservoirs in CD4 + T cells and macrophages. Introducing the concepts of functional and sterile cures, the review underscores the indispensable role of humanized mouse models in HIV research, offering crucial insights into the efficacy of cART and the ongoing pursuit of an HIV cure.</p><p><strong>Recent findings: </strong>Here, we highlight studies investigating molecular mechanisms and pathogenesis related to HIV latency in humanized mice and discuss novel strategies for eradicating latent HIV. Emphasizing the importance of analytical cART interruption in humanized mouse studies to gauge its impact on the latent reservoir accurately, the review underlines the ongoing progress and challenges in harnessing humanized mouse models for HIV research.</p><p><strong>Summary: </strong>This review suggests that humanized mice models provide valuable insights into HIV latency and potential eradication strategies, contributing significantly to the quest for an HIV cure.</p>","PeriodicalId":93966,"journal":{"name":"Current opinion in HIV and AIDS","volume":" ","pages":"157-167"},"PeriodicalIF":0.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140320181","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":"Editorial introduction.","authors":"","doi":"10.1097/COH.0000000000000852","DOIUrl":"https://doi.org/10.1097/COH.0000000000000852","url":null,"abstract":"","PeriodicalId":93966,"journal":{"name":"Current opinion in HIV and AIDS","volume":"19 3","pages":"v-vi"},"PeriodicalIF":0.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141428527","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}