Current opinion in HIV and AIDS最新文献_第10页

HIV-1 subtypes and latent reservoirs. HIV-1 亚型和潜伏库。

Current opinion in HIV and AIDS Pub Date : 2024-03-01 Epub Date: 2023-12-11 DOI: 10.1097/COH.0000000000000835

Udaykumar Ranga, Arun Panchapakesan, Chhavi Saini

{"title":"HIV-1 subtypes and latent reservoirs.","authors":"Udaykumar Ranga, Arun Panchapakesan, Chhavi Saini","doi":"10.1097/COH.0000000000000835","DOIUrl":"10.1097/COH.0000000000000835","url":null,"abstract":"Purpose of review: We explore the current status of research on HIV-1 subtype-specific variations and their impact on HIV-1 latency. We also briefly address the controversy surrounding the decision-making process governing the ON/OFF states of HIV-1 transcription, specifically focusing on the regulatory elements, the long terminal repeat (LTR), and Tat. Understanding the decision-making process is crucial for developing effective intervention strategies, such as the 'shock-and-kill' approach, to reactivate latent HIV-1.Recent findings: Attention has been drawn to subtype-specific transcription factor binding site (TFBS) variations and the possible impact of these variations on viral latency. Further, diverse subtype-specific assays have been developed to quantify the latent viral reservoirs. One interesting observation is the relatively larger latent reservoirs in HIV-1B infection than those of other viral subtypes, which needs rigorous validation. The emergence of LTR-variant viral strains in HIV-1C demonstrating significantly higher levels of latency reversal has been reported.Summary: Despite persistent and substantial efforts, latent HIV-1 remains a formidable challenge to a functional cure. Determined and continued commitment is needed to understand the ON/OFF decision-making process of HIV-1 latency, develop rigorous assays for accurately quantifying the latent reservoirs, and identify potent latency-reversing agents and cocktails targeting multiple latency stages. The review emphasizes the importance of including diverse viral subtypes in future latency research.","PeriodicalId":93966,"journal":{"name":"Current opinion in HIV and AIDS","volume":" ","pages":"87-92"},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139089711","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}

引用次数: 0

Pharmacological approaches to promote cell death of latent HIV reservoirs. 促进潜伏艾滋病病毒库细胞死亡的药理方法。

Current opinion in HIV and AIDS Pub Date : 2024-03-01 Epub Date: 2023-12-20 DOI: 10.1097/COH.0000000000000837

Marilia Rita Pinzone, Liang Shan

{"title":"Pharmacological approaches to promote cell death of latent HIV reservoirs.","authors":"Marilia Rita Pinzone, Liang Shan","doi":"10.1097/COH.0000000000000837","DOIUrl":"10.1097/COH.0000000000000837","url":null,"abstract":"Purpose of review: HIV requires lifelong antiviral treatment due to the persistence of a reservoir of latently infected cells. Multiple strategies have been pursued to promote the death of infected cells.Recent findings: Several groups have focused on multipronged approaches to induce apoptosis of infected cells. One approach is to combine latency reversal agents with proapoptotic compounds and cytotoxic T cells to first reactivate and then clear infected cells. Other strategies include using natural killer cells or chimeric antigen receptor cells to decrease the size of the reservoir.A novel strategy is to promote cell death by pyroptosis. This mechanism relies on the activation of the caspase recruitment domain-containing protein 8 (CARD8) inflammasome by the HIV protease and can be potentiated by nonnucleoside reverse transcriptase inhibitors.Summary: The achievement of a clinically significant reduction in the size of the reservoir will likely require a combination strategy since none of the approaches pursued so far has been successful on its own in clinical trials. This discrepancy between promising in vitro findings and modest in vivo results highlights the hurdles of identifying a universally effective strategy given the wide heterogeneity of the HIV reservoirs in terms of tissue location, capability to undergo latency reversal and susceptibility to cell death.","PeriodicalId":93966,"journal":{"name":"Current opinion in HIV and AIDS","volume":" ","pages":"56-61"},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10872923/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139089712","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}

引用次数: 0

Age at ART initiation and proviral reservoir size in perinatal HIV-1 infection: considerations for ART-free remission. 围产期 HIV-1 感染的抗逆转录病毒疗法起始年龄和病毒库规模：无抗逆转录病毒疗法缓解的考虑因素。

Current opinion in HIV and AIDS Pub Date : 2024-03-01 Epub Date: 2024-01-12 DOI: 10.1097/COH.0000000000000839

Soumia Bekka, Kristen Kelly, Mareike Haaren, Adit Dhummakupt, Deborah Persaud

{"title":"Age at ART initiation and proviral reservoir size in perinatal HIV-1 infection: considerations for ART-free remission.","authors":"Soumia Bekka, Kristen Kelly, Mareike Haaren, Adit Dhummakupt, Deborah Persaud","doi":"10.1097/COH.0000000000000839","DOIUrl":"10.1097/COH.0000000000000839","url":null,"abstract":"Purpose of review: Achieving ART-free remission without the need for lifelong antiretroviral treatment (ART) is a new objective in HIV-1 therapeutics. This review comprehensively examines the literature to evaluate whether the age at ART initiation in children with perinatal HIV-1 influences the size and decay of the HIV-1 reservoir. The insights gathered from this review serve to inform the field on the unique dynamics of HIV-1 reservoir size in perinatal HIV-1 infection as a function of age at ART initiation, as well as inform biomarker profiling and timing of ART-free remission strategies for children living with HIV-1 globally.Recent findings: Recent studies demonstrate that initiating very early effective ART in neonates is feasible and limits HIV-1 reservoir size. The clinical relevance of limiting the HIV-1 reservoir size in perinatal infection was recently demonstrated in the Tatelo Study, which investigated a treatment switch from ART to two broadly neutralizing antibodies (bNAbs) in very early treated children. Low proviral reservoir size was associated with sustained virologic control for 24 weeks on bNAbs.Summary: Immediate and early ART initiation for neonates and infants with perinatal HIV-1 is essential to restricting HIV-1 reservoir size that may enable ART-free remission.","PeriodicalId":93966,"journal":{"name":"Current opinion in HIV and AIDS","volume":" ","pages":"79-86"},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11715321/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139089710","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}

引用次数: 0

Towards an HIV cure: one cell at a time. 实现艾滋病毒的治愈：一次一个细胞。

Current opinion in HIV and AIDS Pub Date : 2024-03-01 Epub Date: 2024-02-08 DOI: 10.1097/COH.0000000000000841

Alberto Bosque

引用次数: 0

Editorial introduction. 编辑介绍。

Current opinion in HIV and AIDS Pub Date : 2024-03-01 Epub Date: 2024-02-08 DOI: 10.1097/COH.0000000000000842

引用次数: 0

Targeting noncoding RNAs to reactivate or eliminate latent HIV reservoirs. 以非编码 RNA 为目标，重新激活或消除潜伏的 HIV 储库。

Current opinion in HIV and AIDS Pub Date : 2024-03-01 Epub Date: 2023-12-20 DOI: 10.1097/COH.0000000000000838

Nadejda Beliakova-Bethell

{"title":"Targeting noncoding RNAs to reactivate or eliminate latent HIV reservoirs.","authors":"Nadejda Beliakova-Bethell","doi":"10.1097/COH.0000000000000838","DOIUrl":"10.1097/COH.0000000000000838","url":null,"abstract":"Purpose of review: Expression of noncoding RNAs (ncRNAs) is more tissue and cell type-specific than expression of protein-coding genes. Understanding the mechanisms of action of ncRNAs and their roles in HIV replication and latency may inform targets for the latent HIV reservoir reactivation or elimination with high specificity to CD4 + T cells latently infected with HIV.Recent findings: While the number of studies in the field of ncRNAs and HIV is limited, evidence points to complex interactions between different ncRNAs, protein-coding RNAs, and proteins. Latency-reversing agents modulate the expression of ncRNAs, with some effects being inhibitory for HIV reactivation. An important limitation of basic research on the ncRNA mechanisms of action is the reliance on cell lines. Because of cell type specificity, it is uncertain whether the ncRNAs function similarly in primary cells.Summary: Comprehensive functional screens to uncover all ncRNAs that regulate HIV expression and the detailed exploration of their mechanisms of action in relevant cell types are needed to identify promising targets for HIV reservoir clearance. Classes of ncRNAs as a whole rather than individual ncRNAs might represent an attractive target for reservoir elimination. Compound screens for latency reversal should factor in the complexity of their effects on ncRNAs.","PeriodicalId":93966,"journal":{"name":"Current opinion in HIV and AIDS","volume":" ","pages":"47-55"},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10872953/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139089714","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}

引用次数: 0

Targeting HIV persistence in the tissue. 针对艾滋病病毒在组织中的持续存在。

Current opinion in HIV and AIDS Pub Date : 2024-03-01 Epub Date: 2024-01-08 DOI: 10.1097/COH.0000000000000836

Daan K J Pieren, Aleix Benítez-Martínez, Meritxell Genescà

{"title":"Targeting HIV persistence in the tissue.","authors":"Daan K J Pieren, Aleix Benítez-Martínez, Meritxell Genescà","doi":"10.1097/COH.0000000000000836","DOIUrl":"10.1097/COH.0000000000000836","url":null,"abstract":"Purpose of review: The complex nature and distribution of the HIV reservoir in tissue of people with HIV remains one of the major obstacles to achieve the elimination of HIV persistence. Challenges include the tissue-specific states of latency and viral persistence, which translates into high levels of reservoir heterogeneity. Moreover, the best strategies to reach and eliminate these reservoirs may differ based on the intrinsic characteristics of the cellular and anatomical reservoir to reach.Recent findings: While major focus has been undertaken for lymphoid tissues and follicular T helper cells, evidence of viral persistence in HIV and non-HIV antigen-specific CD4 + T cells and macrophages resident in multiple tissues providing long-term protection presents new challenges in the quest for an HIV cure. Considering the microenvironments where these cellular reservoirs persist opens new venues for the delivery of drugs and immunotherapies to target these niches. New tools, such as single-cell RNA sequencing, CRISPR screenings, mRNA technology or tissue organoids are quickly developing and providing detailed information about the complex nature of the tissue reservoirs.Summary: Targeting persistence in tissue reservoirs represents a complex but essential step towards achieving HIV cure. Combinatorial strategies, particularly during the early phases of infection to impact initial reservoirs, capable of reaching and reactivating multiple long-lived reservoirs in the body may lead the path.","PeriodicalId":93966,"journal":{"name":"Current opinion in HIV and AIDS","volume":" ","pages":"69-78"},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139089713","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}

引用次数: 0

The pathogenesis of obesity in people living with HIV. 艾滋病毒感染者肥胖的发病机制。

Current opinion in HIV and AIDS Pub Date : 2024-01-01 Epub Date: 2023-11-06 DOI: 10.1097/COH.0000000000000834

Samuel S Bailin, John R Koethe, Peter F Rebeiro

{"title":"The pathogenesis of obesity in people living with HIV.","authors":"Samuel S Bailin, John R Koethe, Peter F Rebeiro","doi":"10.1097/COH.0000000000000834","DOIUrl":"10.1097/COH.0000000000000834","url":null,"abstract":"Purpose of review: The public health challenge of overweight and obesity increasingly affects people living with HIV (PWH). These effects have also accelerated as the prevalence of antiretroviral therapy (ART) use has increased among PWH. It is therefore also critical that we examine and understand the pathogenesis of obesity among PWH.This review will aim to summarize relevant and recent literature related to the risks of weight gain and obesity associated with HIV disease progression, cardiometabolic disease, and multimorbidity among PWH. Further, we will discuss adipose tissue changes associated with weight gain and obesity and how these changes relate to metabolic complications.Recent findings: Several observational and experimental studies in recent years have evaluated the role of contemporary ART regimens, particularly integrase strand transfer inhibitors (INSTIs) and tenofovir alafenamide (TAF), as contributors to weight gain, obesity, and cardiometabolic disease, though the mechanisms remain unclear. Metabolic dysregulation has also been linked to ectopic fat deposition and alterations in innate and adaptive immune cell populations in adipose tissue that accompany HIV and obesity. These factors continue to contribute to an increasing burden of metabolic diseases in an aging HIV population.Summary: Obesity accompanies an increasing burden of metabolic disease among PWH, and understanding the role of fat partitioning and HIV and ART-related adipose tissue dysfunction may guide prevention and treatment strategies.","PeriodicalId":93966,"journal":{"name":"Current opinion in HIV and AIDS","volume":" ","pages":"6-13"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10842175/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71490311","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}

引用次数: 0

Intersections between HIV and obesity in emerging economies. 新兴经济体艾滋病毒与肥胖之间的交叉点。

Current opinion in HIV and AIDS Pub Date : 2024-01-01 Epub Date: 2023-11-03 DOI: 10.1097/COH.0000000000000827

Jacob Levi, Cassandra Fairhead, Andrew Hill

{"title":"Intersections between HIV and obesity in emerging economies.","authors":"Jacob Levi, Cassandra Fairhead, Andrew Hill","doi":"10.1097/COH.0000000000000827","DOIUrl":"10.1097/COH.0000000000000827","url":null,"abstract":"Purpose of review: HIV epidemics are increasing in many emerging economy countries, whilst the very process of 'economic emergence' is obesogenic. Annual deaths related to obesity and overweight are now four times more than for HIV globally. We describe the intersections between HIV and obesity in emerging economies, and highlight potential mitigation options, including antiobesity medications (AOMs), which are safe and effective, but inaccessibly priced.Recent findings: We summarize what is known about weight-change in HIV and review strategies including public health policies and clinical interventions for emerging economy countries to fight obesity. We also illustrate the landscape from a selection of 'emerging economy' countries with available data from UNAIDS, World Bank and World Obesity Federation to visualize the developing challenges faced. AOM course prices are high in many countries, but could be manufactured and sold profitably for much less. We present lessons from the early HIV/AIDS movements on how to improve access and pricing for AOMs for people with HIV with obesity in emerging economy countries.Summary: We illustrate the complex intersectional issues that 'emerging economy countries' may experience, with a 'double burden' of increasing HIV and obesity epidemics, and explore potential mitigation options, focussing on AOM access and pricing.","PeriodicalId":93966,"journal":{"name":"Current opinion in HIV and AIDS","volume":" ","pages":"35-44"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71435044","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}

引用次数: 0

Clinical consequences of weight gain during treatment for HIV infection. HIV感染治疗期间体重增加的临床后果。

Current opinion in HIV and AIDS Pub Date : 2024-01-01 Epub Date: 2023-11-06 DOI: 10.1097/COH.0000000000000829

Andrew Hill, Willem Daniel Francois Venter

{"title":"Clinical consequences of weight gain during treatment for HIV infection.","authors":"Andrew Hill, Willem Daniel Francois Venter","doi":"10.1097/COH.0000000000000829","DOIUrl":"10.1097/COH.0000000000000829","url":null,"abstract":"Purpose of review: The introduction of dolutegravir, an oral integrase inhibitor, within public health HIV programs has been a success, with excellent sustained viral load suppression, persistence, and safety. Initial concerns around integrase-inhibitors being implicated in safety concerns around immune reconstitution inflammatory syndromes (IRIS), neural tube defects, and weight gain, have been largely laid to rest, but new concerns about cardiovascular risk have arisen, including a link between hypertension and this antiretroviral class.Recent findings: We review the pertinent studies here, and while we find both observational and randomized controlled study associations in some but not all studies, these are often confounded by associated weight gain and aging. In addition, definitions of hypertension, as well as measurement within the studies (such as cuff size), were not consistent within studies.Summary: Careful analysis will be needed, as with the weight-gain signal, before assigning causation, especially as plausible physiological mechanisms for this rise in blood pressure are unclear.","PeriodicalId":93966,"journal":{"name":"Current opinion in HIV and AIDS","volume":" ","pages":"21-29"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71490310","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}

引用次数: 0