Safety and efficacy of VRC01 broadly neutralising antibodies in adults with acutely treated HIV (RV397): a phase 2, randomised, double-blind, placebo-controlled trial.
Adult
Antibodies, Monoclonal
/ drug effects
Antibodies, Neutralizing
/ immunology
Antibodies, Viral
/ immunology
Antiretroviral Therapy, Highly Active
Broadly Neutralizing Antibodies
/ drug effects
CD4 Lymphocyte Count
CD4-Positive T-Lymphocytes
Female
HIV Antibodies
/ drug effects
HIV Infections
/ drug therapy
HIV-1
/ immunology
Humans
Male
Middle Aged
Treatment Outcome
Viral Load
Young Adult
Journal
The lancet. HIV
ISSN: 2352-3018
Titre abrégé: Lancet HIV
Pays: Netherlands
ID NLM: 101645355
Informations de publication
Date de publication:
05 2019
05 2019
Historique:
received:
19
11
2018
revised:
06
02
2019
accepted:
12
02
2019
pubmed:
20
4
2019
medline:
2
6
2020
entrez:
20
4
2019
Statut:
ppublish
Résumé
HIV-1-specific broadly neutralising antibodies such as VRC01 could promote HIV remission by halting viral replication and clearing infected cells. We investigated whether VRC01 could promote sustained viral control off antiretroviral therapy (ART) in adults who initiated ART during acute HIV infection. We did a randomised, double-blind, placebo-controlled trial at the Thai Red Cross AIDS Research Centre in Bangkok, Thailand. Eligible participants were aged 20-50 years, had initiated ART during acute infection (ie, Fiebig stages I-III), had been taking ART for more than 24 months, had fewer than 50 HIV-1 RNA copies per mL on three consecutive measurements, had more than 400 CD4 cells per μL, had fewer than ten copies of integrated HIV-1 DNA per 10 Between Aug 8, 2016, and Jan 9, 2017, 19 men were randomly assigned, 14 to the VRC01 group and five to the placebo group. One participant in the VRC01 group received a partial infusion without undergoing treatment interruption. The other 18 participants all received at least one full study infusion and underwent ART interruption. No serious adverse events were reported in either group. Only one participant in the VRC01 group achieved the primary efficacy endpoint of viral suppression 24 weeks after ART interruption. The other 17 restarted ART because of a confirmed recording of 1000 or more HIV-1 RNA copies per mL before 24 weeks. VRC01 monotherapy in individuals who initiated ART during acute HIV infection was well tolerated but did not significantly increase the number of participants with viral suppression 24 weeks after ART interruption. Further development of VRC01 and other immunotherapies for HIV will probably occur as part of combination regimens that include several treatments directed against unique therapeutic targets. US Department of the Army, US National Institutes of Health, and the Thai Red Cross AIDS Research Centre.
Sections du résumé
BACKGROUND
HIV-1-specific broadly neutralising antibodies such as VRC01 could promote HIV remission by halting viral replication and clearing infected cells. We investigated whether VRC01 could promote sustained viral control off antiretroviral therapy (ART) in adults who initiated ART during acute HIV infection.
METHODS
We did a randomised, double-blind, placebo-controlled trial at the Thai Red Cross AIDS Research Centre in Bangkok, Thailand. Eligible participants were aged 20-50 years, had initiated ART during acute infection (ie, Fiebig stages I-III), had been taking ART for more than 24 months, had fewer than 50 HIV-1 RNA copies per mL on three consecutive measurements, had more than 400 CD4 cells per μL, had fewer than ten copies of integrated HIV-1 DNA per 10
FINDINGS
Between Aug 8, 2016, and Jan 9, 2017, 19 men were randomly assigned, 14 to the VRC01 group and five to the placebo group. One participant in the VRC01 group received a partial infusion without undergoing treatment interruption. The other 18 participants all received at least one full study infusion and underwent ART interruption. No serious adverse events were reported in either group. Only one participant in the VRC01 group achieved the primary efficacy endpoint of viral suppression 24 weeks after ART interruption. The other 17 restarted ART because of a confirmed recording of 1000 or more HIV-1 RNA copies per mL before 24 weeks.
INTERPRETATION
VRC01 monotherapy in individuals who initiated ART during acute HIV infection was well tolerated but did not significantly increase the number of participants with viral suppression 24 weeks after ART interruption. Further development of VRC01 and other immunotherapies for HIV will probably occur as part of combination regimens that include several treatments directed against unique therapeutic targets.
FUNDING
US Department of the Army, US National Institutes of Health, and the Thai Red Cross AIDS Research Centre.
Identifiants
pubmed: 31000477
pii: S2352-3018(19)30053-0
doi: 10.1016/S2352-3018(19)30053-0
pmc: PMC6693657
mid: NIHMS1527265
pii:
doi:
Substances chimiques
Antibodies, Monoclonal
0
Antibodies, Neutralizing
0
Antibodies, Viral
0
Broadly Neutralizing Antibodies
0
HIV Antibodies
0
VRC01 monoclonal antibody
0
Banques de données
ClinicalTrials.gov
['NCT02664415']
Types de publication
Clinical Trial
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
e297-e306Subventions
Organisme : NIAID NIH HHS
ID : R01 AI108433
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI096109
Pays : United States
Organisme : CCR NIH HHS
ID : HHSN261200800001C
Pays : United States
Organisme : NIAID NIH HHS
ID : L30 AI120129
Pays : United States
Organisme : NCI NIH HHS
ID : HHSN261200800001E
Pays : United States
Investigateurs
Julie A Ake
(JA)
Siriwat Akapirat
(S)
Meera Bose
(M)
Evan Cale
(E)
Phillip Chan
(P)
Sararut Chanthaburanun
(S)
Nampueng Churikanont
(N)
Peter Dawson
(P)
Netsiri Dumrongpisutikul
(N)
Saowanit Getchalarat
(S)
Surat Jongrakthaitae
(S)
Krisada Jongsakul
(K)
Sukalaya Lerdlum
(S)
Sopark Manasnayakorn
(S)
Corinne McCullough
(C)
Mark Milazzo
(M)
Bessara Nuntapinit
(B)
Kier On
(K)
Madelaine Ouellette
(M)
Praphan Phanuphak
(P)
Eric Sanders-Buell
(E)
Nongluck Sangnoi
(N)
Shida Shangguan
(S)
Sunee Sirivichayakul
(S)
Nipattra Tragonlugsana
(N)
Rapee Trichavaroj
(R)
Sasiwimol Ubolyam
(S)
Sandhya Vasan
(S)
Phandee Wattanaboonyongcharoen
(P)
Thipvadee Yamchuenpong
(T)
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2019 Elsevier Ltd. All rights reserved.