This study will be a two-arm prospective 1:1 randomised controlled trial comparing:
Arm A: cART preferably including raltegravir (combination ART cART - control) Arm B: cART preferably including raltegravir (cART) plus ChAdV63.HIVconsv (ChAd) prime and MVA.HIVconsv (MVA) boost vaccines; followed by a 28-day course of vorinostat (10 doses in total).
We hypothesise that this intervention in primary HIV infection will confer a significant reduction in the latent HIV reservoir when compared with cART alone.
.

开始日期2015-11-27

申办/合作机构

Imperial College London

[+8]

NCT02362217

/ Completed临床1期IIT

A Phase I Study to Evaluate the Safety and Immunogenicity of Simultaneous Prime-Boost Immunisations With Candidate HCV and HIV-1 Vaccines, AdCh3NSmut1 / ChAdV63.HIVconsv and MVA-NSmut / MVA.HIVconsv, in Healthy Volunteers

This study is aimed at assessing the safety of candidate Hepatitis C vaccines AdCh3NSmut/MVA-NSmut and HIV vaccines ChAdV63.HIVconsv/MVA.HIVconsv when administered separately or in combination to healthy volunteers. The study also aims to assess the cellular immune response generated by these vaccines when administered as mentioned above.

开始日期2014-10-01

申办/合作机构

University of Oxford

[+2]

NCT01712425

/ Completed临床1期IIT

Safety and Immunogenicity of ChAdV63.HIVconsv and MVA.HIVconsv Candidate HIV-1 Vaccines in Recently HIV-1 Infected Individuals With Early Viral Suppression After Initiation of Antiretroviral Therapy (HAART)

The HIVconsv gene was constructed by assembling the 14 most conserved regions of the HIV-1 proteome into one chimaeric protein. This gene has been inserted into 2 leading non-replicating vaccine vectors: an attenuated chimpanzee adenovirus serotype 63 (ChAdV63) and a modified vaccinia virus Ankara (MVA) to construct the ChAdV63.HIVconsv and MVA.HIVconsv HIV-1 candidate vaccines. The present study is named ChAd-MVA.HIVconsv-BCN01 and it is a phase I, multicenter primary/booster therapeutic vaccination study to evaluate the safety and immunogenicity of ChAdV63.HIVcons and MVA.HIVconsv HIV-1 vaccines, delivered intramuscularly according to a 0-8 weeks or a 0-24 weeks schedule to recently HIV-1 infected individuals with early viral suppression 6 months after initiation of Tenofovir/Emtricitabine plus Raltegravir.

开始日期2012-10-01

申办/合作机构

IrsiCaixa AIDS Research Institute

[+2]

100 项与 MVA.HIVconsv vaccine(University of Oxford) 相关的临床结果

登录后查看更多信息

100 项与 MVA.HIVconsv vaccine(University of Oxford) 相关的转化医学

登录后查看更多信息

100 项与 MVA.HIVconsv vaccine(University of Oxford) 相关的专利（医药）

登录后查看更多信息

项与 MVA.HIVconsv vaccine(University of Oxford) 相关的文献（医药）

2022-12-01·Microbiome1区 · 生物学

Gut microbiome signatures linked to HIV-1 reservoir size and viremia control

1区 · 生物学

ArticleOA

作者: Parera, Mariona ; Brander, Christian ; Noguera-Julian, Marc ; Moltó, José ; Paredes, Roger ; Oriol, Bruna ; Duran, Clara ; Birse, Kenzie ; Clotet, Bonaventura ; Casadellà, Maria ; Mothe, Beatriz ; De Leon, Marlon ; Català-Moll, Francesc ; Martinez-Picado, Javier ; Guillén, Yolanda ; Borgognone, Alessandra ; Manzardo, Christian ; Noël-Romas, Laura ; Puertas, Maria C ; Ruiz-Riol, Marta ; Miró, José M ; Knodel, Samantha ; Burgener, Adam

AbstractBackgroundThe potential role of the gut microbiome as a predictor of immune-mediated HIV-1 control in the absence of antiretroviral therapy (ART) is still unknown. In the BCN02 clinical trial, which combined the MVA.HIVconsv immunogen with the latency-reversing agent romidepsin in early-ART treated HIV-1 infected individuals, 23% (3/13) of participants showed sustained low-levels of plasma viremia during 32 weeks of a monitored ART pause (MAP). Here, we present a multi-omics analysis to identify compositional and functional gut microbiome patterns associated with HIV-1 control in the BCN02 trial.ResultsViremic controllers during the MAP (controllers) exhibited higher Bacteroidales/Clostridiales ratio and lower microbial gene richness before vaccination and throughout the study intervention when compared to non-controllers. Longitudinal assessment indicated that the gut microbiome of controllers was enriched in pro-inflammatory bacteria and depleted in butyrate-producing bacteria and methanogenic archaea. Functional profiling also showed that metabolic pathways related to fatty acid and lipid biosynthesis were significantly increased in controllers. Fecal metaproteome analyses confirmed that baseline functional differences were mainly driven by Clostridiales. Participants with high baseline Bacteroidales/Clostridiales ratio had increased pre-existing immune activation-related transcripts. The Bacteroidales/Clostridiales ratio as well as host immune-activation signatures inversely correlated with HIV-1 reservoir size.ConclusionsThe present proof-of-concept study suggests the Bacteroidales/Clostridiales ratio as a novel gut microbiome signature associated with HIV-1 reservoir size and immune-mediated viral control after ART interruption.

2022-03-01·AIDS2区 · 医学

Preserved central nervous system functioning after use of romidepsin as a latency-reversing agent in an HIV cure strategy

2区 · 医学

Article

作者: Carrillo-Molina, Sara ; Meulbroek, Michael ; Brander, Christian ; Muñoz-Moreno, Jose A. ; Moltó, José ; Martínez-Zalacaín, Ignacio ; Coll, Pep ; Hanke, Tomáš ; Miró, Josep M. ; Soriano-Mas, Carles ; Manzardo, Christian ; Garolera, Maite ; Miranda, Cristina ; Mothe, Beatriz ; Clotet, Bonaventura

Objective:To assess the central nervous system (CNS) impact of a kick&kill HIV cure strategy using therapeutic vaccine MVA.HIVconsv and the histone deacetylase inhibitor (HDACi) romidepsin (RMD) as latency-reversing agent.Design:Neurological observational substudy of the BCN02 trial (NCT02616874), a proof-of-concept, open-label, single-arm, phase I clinical trial testing the safety and immunogenicity of the MVA.HIVconsv vaccine and RMD in early-treated HIV-1-infected individuals. A monitored antiretroviral pause (MAP) was performed, with cART resumption after 2 pVL more than 2000 copies/ml. Reinitiated participants were followed for 24 weeks.Methods:Substudy participation was offered to all BCN02 participants (N = 15). Evaluations covered cognitive, functional, and brain imaging outcomes, performed before RMD administration (pre-RMD), after three RMD infusions (post-RMD), and at the end of the study (EoS). A group of early-treated HIV-1-infected individuals with matched clinical characteristics was additionally recruited (n = 10). Primary endpoint was change in a global cognitive score (NPZ-6).Results:Eleven participants from BCN02 trial were enrolled. No significant changes were observed in cognitive, functional, or brain imaging outcomes from pre-RMD to post-RMD. No relevant alterations were detected from pre-RMD to EoS either. Scores at EoS were similar in participants off cART for 32 weeks (n = 3) and those who resumed therapy for 24 weeks (n = 7). Controls showed comparable punctuations in NPZ-6 across all timepoints.Conclusion:No detrimental effects on cognitive status, functional outcomes, or brain imaging parameters were observed after using the HDACi RMD as latency-reversing agent with the MVA.HIVconsv vaccine in early-treated HIV-1-infected individuals. CNS safety was also confirmed after completion of the MAP.

2020-03-01·The Lancet1区 · 医学

Antiretroviral therapy alone versus antiretroviral therapy with a kick and kill approach, on measures of the HIV reservoir in participants with recent HIV infection (the RIVER trial): a phase 2, randomised trial

1区 · 医学

Article

作者: Kelly, Damian ; Collins, Simon ; Fitzpatrick, Colin ; O'Rourke, Patrick ; Wills, Mark ; Topping, Katie ; Babiker, Abdel ; Kinloch-de Loes, Sabine ; Hague, Dominic ; Merle, Simon ; Gleig, Rebecca ; Finnerty, Fiounnuala ; Lever, Andrew ; Cuthbertson, Zoe ; Ngwu, Nnenna ; Howell, Bonnie ; Anderson, Jane ; Murray, Tammy ; Erlwein, Otto ; Robinson, Nicola ; Weller, Ian ; Fisher, Martin ; Crook, Alison ; Adams, Tanya ; Trevitt, Vittorio ; Fedele, Serge ; Jendrulek, Isabel ; Box, Hanna ; Sasieni, Peter ; Markham, Alex ; Nwokolo, Nneka ; Thomas, Lervina ; McClure, Myra ; Lukha, Hinal ; Darbyshire, Janet ; Brown, Helen ; Nightingale, Alice ; Schoolmeesters, Alexandra ; Hudson, Fleur ; Sandström, Eric ; Johnson, Margaret ; Rowlands, Jane ; Pace, Matt ; Post, Frank ; Olejniczak, Natalia ; Conlon, Christopher ; Uzu, Hiromi ; Kingsley, Cherry ; Peto, Timothy ; Pace, Matthew ; Shidfar, Shaadi ; Cerrone, Maddalena ; Weaver, Christine ; Gregory, Adam ; Jones, Martin ; Khan, Maryam ; Frater, John ; Lwanga, Julianne ; Kaye, Steven ; Taylor, Mark ; Pett, Sarah ; Lewis, Heather ; Thunder, Orla ; Kuldanek, Kristin ; Wu, Guoxin ; Sy, Aminata ; Sowunmi, Yinka ; Barnard, Richard ; Russell, Charlotte ; Higgs, Christopher ; Wood, Gemma ; Fidler, Sarah ; Clarke, Amanda ; Castrillo Martinez, Nadia ; Miller, Veronica ; Bennett, Rachel ; Fiorino, Marzia ; Hanke, Tomáš ; Bandara, Mikaila ; Tiraboschi, Juan Manuel ; Lawrenson, Gaynor ; Fun, Axel ; Bracchi, Margherita ; Fernandez, Tina ; Lovell, Andrew ; Thornhill, John ; Gabrielle, Michelle ; Bourke, Peter ; ZarkoFlynn, Taras ; Fox, Julie ; Stöhr, Wolfgang ; Yang, Hongbing ; Lee, Ming ; Maini, Mala ; Kopycinski, Jakub ; Dorrell, Lucy ; Kaye, Steve ; Rauchenberger, Mary ; Byrne, Patrick ; Nelson, Mark ; Barber, Tristan

BACKGROUNDAntiretroviral therapy (ART) cannot cure HIV infection because of a persistent reservoir of latently infected cells. Approaches that force HIV transcription from these cells, making them susceptible to killing-termed kick and kill regimens-have been explored as a strategy towards an HIV cure. RIVER is the first randomised trial to determine the effect of ART-only versus ART plus kick and kill on markers of the HIV reservoir.METHODSThis phase 2, open-label, multicentre, randomised, controlled trial was undertaken at six clinical sites in the UK. Patients aged 18-60 years who were confirmed as HIV-positive within a maximum of the past 6 months and started ART within 1 month from confirmed diagnosis were randomly assigned by a computer generated randomisation list to receive ART-only (control) or ART plus the histone deacetylase inhibitor vorinostat (the kick) and replication-deficient viral vector T-cell inducing vaccines encoding conserved HIV sequences ChAdV63. HIVconsv-prime and MVA.HIVconsv-boost (the kill; ART + V + V; intervention). The primary endpoint was total HIV DNA isolated from peripheral blood CD4⁺ T-cells at weeks 16 and 18 after randomisation. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, NCT02336074.FINDINGSBetween June 14, 2015 and Jul 11, 2017, 60 men with HIV were randomly assigned to receive either an ART-only (n=30) or an ART + V + V (n=30) regimen; all 60 participants completed the study, with no loss-to-follow-up. Mean total HIV DNA at weeks 16 and 18 after randomisation was 3·02 log₁₀ copies HIV DNA per 10⁶ CD4⁺ T-cells in the ART-only group versus 3·06 log₁₀ copies HIV DNA per 10⁶ CD4⁺ T-cells in ART + V + V group, with no statistically significant difference between the two groups (mean difference of 0·04 log₁₀ copies HIV DNA per 10⁶ CD4⁺ T-cells [95% CI -0·03 to 0·11; p=0·26]). There were no intervention-related serious adverse events.INTERPRETATIONThis kick and kill approach conferred no significant benefit compared with ART alone on measures of the HIV reservoir. Although this does not disprove the efficacy kick and kill strategy, for future trials enhancement of both kick and kill agents will be required.FUNDINGMedical Research Council (MR/L00528X/1).

100 项与 MVA.HIVconsv vaccine(University of Oxford) 相关的药物交易

登录后查看更多信息

研发状态

10 条进展最快的记录,

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
HIV感染	临床2期	英国	University of Oxford	2015-11-27

登录后查看更多信息

临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT02336074 (RIVER, CTgov)	临床2期	HIV感染	60	Combination Antiretroviral Therapy (cART)+raltegravir (Control)	醖廠鑰鑰鬱構選顧鑰鏇(鑰齋艱製窪鬱壓鏇範鬱) = 齋觸憲壓淵襯簾顧壓網積範鹽壓壓糧廠齋遞顧 (觸鹹獵鏇鬱壓觸憲鏇糧, 廠範廠醖壓膚膚鏇願夢 ~ 範網觸選蓋繭壓艱築鹹) 更多	-	2019-09-25
				Combination Antiretroviral Therapy (cART)+Vorinostat+MVA.HIVconsv (MVA)+ChAdV63.HIVconsv (ChAd)+raltegravir (Intervention)	醖廠鑰鑰鬱構選顧鑰鏇(鑰齋艱製窪鬱壓鏇範鬱) = 獵膚選選壓壓艱夢夢願積範鹽壓壓糧廠齋遞顧 (觸鹹獵鏇鬱壓觸憲鏇糧, 廠衊淵觸餘蓋製齋顧鏇 ~ 選糧糧壓簾廠鑰鬱獵選) 更多