PMID- 36302893
OWN - NLM
STAT- MEDLINE
DCOM- 20230102
LR  - 20230315
IS  - 1546-170X (Electronic)
IS  - 1078-8956 (Linking)
VI  - 28
IP  - 12
DP  - 2022 Dec
TI  - Safety, immunogenicity and effect on viral rebound of HTI vaccines in early 
      treated HIV-1 infection: a randomized, placebo-controlled phase 1 trial.
PG  - 2611-2621
LID - 10.1038/s41591-022-02060-2 [doi]
AB  - HIVACAT T-cell immunogen (HTI) is a novel human immunodeficiency virus (HIV) 
      vaccine immunogen designed to elicit cellular immune responses to HIV targets 
      associated with viral control in humans. The AELIX-002 trial was a randomized, 
      placebo-controlled trial to evaluate as a primary objective the safety of a 
      combination of DNA.HTI (D), MVA.HTI (M) and ChAdOx1.HTI (C) vaccines in 45 
      early-antiretroviral (ART)-treated individuals (44 men, 1 woman; NCT03204617). 
      Secondary objectives included T-cell immunogenicity, the effect on viral rebound 
      and the safety of an antiretroviral treatment interruption (ATI). Adverse events 
      were mostly mild and transient. No related serious adverse events were observed. 
      We show here that HTI vaccines were able to induce strong, polyfunctional and 
      broad CD4 and CD8 T-cell responses. All participants experienced detectable viral 
      rebound during ATI, and resumed ART when plasma HIV-1 viral load reached either 
      >100,000 copies ml(-1), >10,000 copies ml(-1) for eight consecutive weeks, or 
      after 24 weeks of ATI. In post-hoc analyses, HTI vaccines were associated with a 
      prolonged time off ART in vaccinees without beneficial HLA (human leukocyte 
      antigen) class I alleles. Plasma viral load at the end of ATI and time off ART 
      positively correlated with vaccine-induced HTI-specific T-cell responses at ART 
      cessation. Despite limited efficacy of the vaccines in preventing viral rebound, 
      their ability to elicit robust T-cell responses towards HTI may be beneficial in 
      combination cure strategies, which are currently being tested in clinical trials.
CI  - (c) 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.
FAU - Bailon, Lucia
AU  - Bailon L
AUID- ORCID: 0000-0001-7277-9314
AD  - Fundacio Lluita Contra les Infeccions, Infectious Diseases Department, Hospital 
      Universitari Germans Trias I Pujol, Badalona, Barcelona, Spain.
AD  - Department of Medicine, Autonomous University of Barcelona, Catalonia, Spain.
FAU - Llano, Anuska
AU  - Llano A
AUID- ORCID: 0000-0002-0133-9888
AD  - IrsiCaixa AIDS Research Institute, Hospital Universitari Germans Trias I Pujol, 
      Badalona, Barcelona, Spain.
FAU - Cedeno, Samandhy
AU  - Cedeno S
AUID- ORCID: 0000-0001-8312-0208
AD  - IrsiCaixa AIDS Research Institute, Hospital Universitari Germans Trias I Pujol, 
      Badalona, Barcelona, Spain.
FAU - Escriba, Tuixent
AU  - Escriba T
AUID- ORCID: 0000-0001-9467-7802
AD  - IrsiCaixa AIDS Research Institute, Hospital Universitari Germans Trias I Pujol, 
      Badalona, Barcelona, Spain.
FAU - Rosas-Umbert, Miriam
AU  - Rosas-Umbert M
AUID- ORCID: 0000-0002-2850-6586
AD  - IrsiCaixa AIDS Research Institute, Hospital Universitari Germans Trias I Pujol, 
      Badalona, Barcelona, Spain.
AD  - Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark.
FAU - Parera, Mariona
AU  - Parera M
AD  - IrsiCaixa AIDS Research Institute, Hospital Universitari Germans Trias I Pujol, 
      Badalona, Barcelona, Spain.
FAU - Casadella, Maria
AU  - Casadella M
AUID- ORCID: 0000-0002-4115-2305
AD  - IrsiCaixa AIDS Research Institute, Hospital Universitari Germans Trias I Pujol, 
      Badalona, Barcelona, Spain.
FAU - Lopez, Miriam
AU  - Lopez M
AD  - Fundacio Lluita Contra les Infeccions, Infectious Diseases Department, Hospital 
      Universitari Germans Trias I Pujol, Badalona, Barcelona, Spain.
FAU - Perez, Francisco
AU  - Perez F
AD  - Fundacio Lluita Contra les Infeccions, Infectious Diseases Department, Hospital 
      Universitari Germans Trias I Pujol, Badalona, Barcelona, Spain.
FAU - Oriol-Tordera, Bruna
AU  - Oriol-Tordera B
AUID- ORCID: 0000-0002-2714-9097
AD  - IrsiCaixa AIDS Research Institute, Hospital Universitari Germans Trias I Pujol, 
      Badalona, Barcelona, Spain.
FAU - Ruiz-Riol, Marta
AU  - Ruiz-Riol M
AD  - IrsiCaixa AIDS Research Institute, Hospital Universitari Germans Trias I Pujol, 
      Badalona, Barcelona, Spain.
AD  - CIBERINFEC, ISCIII, Madrid, Spain.
FAU - Coll, Josep
AU  - Coll J
AD  - IrsiCaixa AIDS Research Institute, Hospital Universitari Germans Trias I Pujol, 
      Badalona, Barcelona, Spain.
AD  - CIBERINFEC, ISCIII, Madrid, Spain.
AD  - Projecte Dels Noms-Hispanosida, Bcn Checkpoint, Barcelona, Spain.
FAU - Perez, Felix
AU  - Perez F
AD  - Projecte Dels Noms-Hispanosida, Bcn Checkpoint, Barcelona, Spain.
FAU - Rivero, Angel
AU  - Rivero A
AD  - Projecte Dels Noms-Hispanosida, Bcn Checkpoint, Barcelona, Spain.
FAU - Leselbaum, Anne R
AU  - Leselbaum AR
AD  - Projecte Dels Noms-Hispanosida, Bcn Checkpoint, Barcelona, Spain.
FAU - McGowan, Ian
AU  - McGowan I
AUID- ORCID: 0000-0002-6470-8476
AD  - AELIX Therapeutics S.L, Barcelona, Spain.
AD  - University of Pittsburgh, Pittsburgh, PA, USA.
FAU - Sengupta, Devi
AU  - Sengupta D
AD  - Gilead Sciences, Inc, Foster City, CA, USA.
FAU - Wee, Edmund G
AU  - Wee EG
AD  - The Jenner Institute, The Nuffield Department of Medicine, University of Oxford, 
      Oxford, UK.
FAU - Hanke, Tomas
AU  - Hanke T
AUID- ORCID: 0000-0002-6076-9546
AD  - The Jenner Institute, The Nuffield Department of Medicine, University of Oxford, 
      Oxford, UK.
AD  - Joint Research Center for Human Retrovirus Infection, Kumamoto University, 
      Kumamoto, Japan.
FAU - Paredes, Roger
AU  - Paredes R
AUID- ORCID: 0000-0002-6553-691X
AD  - IrsiCaixa AIDS Research Institute, Hospital Universitari Germans Trias I Pujol, 
      Badalona, Barcelona, Spain.
AD  - CIBERINFEC, ISCIII, Madrid, Spain.
AD  - Centre for Health and Social Care Research (CESS), Faculty of Medicine. 
      University of Vic - Central University of Catalonia (UVic - UCC), Vic, Barcelona, 
      Spain.
AD  - Germans Trias I Pujol Research Institte, Badalona, Spain.
FAU - Alarcon-Soto, Yovaninna
AU  - Alarcon-Soto Y
AUID- ORCID: 0000-0002-9977-8634
AD  - Fundacio Lluita Contra les Infeccions, Infectious Diseases Department, Hospital 
      Universitari Germans Trias I Pujol, Badalona, Barcelona, Spain.
AD  - Departament d'Estadistica I Investigacio Operativa, Universitat Politecnica de 
      Catalunya/BARCELONATECH, Barcelona, Spain.
FAU - Clotet, Bonaventura
AU  - Clotet B
AUID- ORCID: 0000-0003-3232-4598
AD  - Fundacio Lluita Contra les Infeccions, Infectious Diseases Department, Hospital 
      Universitari Germans Trias I Pujol, Badalona, Barcelona, Spain.
AD  - IrsiCaixa AIDS Research Institute, Hospital Universitari Germans Trias I Pujol, 
      Badalona, Barcelona, Spain.
AD  - CIBERINFEC, ISCIII, Madrid, Spain.
AD  - Centre for Health and Social Care Research (CESS), Faculty of Medicine. 
      University of Vic - Central University of Catalonia (UVic - UCC), Vic, Barcelona, 
      Spain.
FAU - Noguera-Julian, Marc
AU  - Noguera-Julian M
AUID- ORCID: 0000-0002-6194-1395
AD  - IrsiCaixa AIDS Research Institute, Hospital Universitari Germans Trias I Pujol, 
      Badalona, Barcelona, Spain.
AD  - CIBERINFEC, ISCIII, Madrid, Spain.
AD  - Centre for Health and Social Care Research (CESS), Faculty of Medicine. 
      University of Vic - Central University of Catalonia (UVic - UCC), Vic, Barcelona, 
      Spain.
FAU - Brander, Christian
AU  - Brander C
AUID- ORCID: 0000-0002-0548-5778
AD  - IrsiCaixa AIDS Research Institute, Hospital Universitari Germans Trias I Pujol, 
      Badalona, Barcelona, Spain.
AD  - CIBERINFEC, ISCIII, Madrid, Spain.
AD  - AELIX Therapeutics S.L, Barcelona, Spain.
AD  - Centre for Health and Social Care Research (CESS), Faculty of Medicine. 
      University of Vic - Central University of Catalonia (UVic - UCC), Vic, Barcelona, 
      Spain.
AD  - ICREA, Barcelona, Spain.
FAU - Molto, Jose
AU  - Molto J
AD  - Fundacio Lluita Contra les Infeccions, Infectious Diseases Department, Hospital 
      Universitari Germans Trias I Pujol, Badalona, Barcelona, Spain. 
      jmolto@lluita.org.
AD  - CIBERINFEC, ISCIII, Madrid, Spain. jmolto@lluita.org.
AD  - Germans Trias I Pujol Research Institte, Badalona, Spain. jmolto@lluita.org.
FAU - Mothe, Beatriz
AU  - Mothe B
AUID- ORCID: 0000-0001-9975-407X
AD  - Fundacio Lluita Contra les Infeccions, Infectious Diseases Department, Hospital 
      Universitari Germans Trias I Pujol, Badalona, Barcelona, Spain.
AD  - IrsiCaixa AIDS Research Institute, Hospital Universitari Germans Trias I Pujol, 
      Badalona, Barcelona, Spain.
AD  - CIBERINFEC, ISCIII, Madrid, Spain.
AD  - Centre for Health and Social Care Research (CESS), Faculty of Medicine. 
      University of Vic - Central University of Catalonia (UVic - UCC), Vic, Barcelona, 
      Spain.
AD  - Germans Trias I Pujol Research Institte, Badalona, Spain.
CN  - AELIX002 Study Group
LA  - eng
SI  - ClinicalTrials.gov/NCT03204617
GR  - MR/N023668/1/MRC_/Medical Research Council/United Kingdom
GR  - P01 AI131568/AI/NIAID NIH HHS/United States
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20221027
PL  - United States
TA  - Nat Med
JT  - Nature medicine
JID - 9502015
RN  - 0 (Anti-Retroviral Agents)
RN  - 0 (Vaccines)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (AIDS Vaccines)
SB  - IM
MH  - Male
MH  - Female
MH  - Humans
MH  - *HIV-1
MH  - *HIV Infections
MH  - CD8-Positive T-Lymphocytes
MH  - Anti-Retroviral Agents/therapeutic use
MH  - *Vaccines/therapeutic use
MH  - Histocompatibility Antigens Class I
MH  - Viral Load
MH  - CD4-Positive T-Lymphocytes
MH  - *AIDS Vaccines
FIR - Barriocanal, Ana Maria
IR  - Barriocanal AM
FIR - Benet, Susana
IR  - Benet S
FIR - Cobarsi, Patricia
IR  - Cobarsi P
FIR - Geleziunas, Romas
IR  - Geleziunas R
FIR - Leselbaum, Anne R
IR  - Leselbaum AR
FIR - Loste, Cora
IR  - Loste C
FIR - Meulbroek, Michael
IR  - Meulbroek M
FIR - Miranda, Cristina
IR  - Miranda C
FIR - Munoz, Jose
IR  - Munoz J
FIR - Naval, Jordi
IR  - Naval J
FIR - Nieto, Aroa
IR  - Nieto A
FIR - Pujol, Ferran
IR  - Pujol F
FIR - Puig, Jordi
IR  - Puig J
EDAT- 2022/10/28 06:00
MHDA- 2023/01/03 06:00
CRDT- 2022/10/27 23:38
PHST- 2021/11/03 00:00 [received]
PHST- 2022/09/28 00:00 [accepted]
PHST- 2022/10/28 06:00 [pubmed]
PHST- 2023/01/03 06:00 [medline]
PHST- 2022/10/27 23:38 [entrez]
AID - 10.1038/s41591-022-02060-2 [pii]
AID - 10.1038/s41591-022-02060-2 [doi]
PST - ppublish
SO  - Nat Med. 2022 Dec;28(12):2611-2621. doi: 10.1038/s41591-022-02060-2. Epub 2022 
      Oct 27.