Design of an optimal combination therapy with broadly neutralizing antibodies to suppress HIV-1.
HIV combination therapy
broadly neutralizing antibody
evolutionary biology
evolutionary control
human
optimization
physics of living systems
population genetics
stochastic processes
viruses
Journal
eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614
Informations de publication
Date de publication:
19 07 2022
19 07 2022
Historique:
received:
01
12
2021
accepted:
04
07
2022
pubmed:
20
7
2022
medline:
15
9
2022
entrez:
19
7
2022
Statut:
epublish
Résumé
Infusion of broadly neutralizing antibodies (bNAbs) has shown promise as an alternative to anti-retroviral therapy against HIV. A key challenge is to suppress viral escape, which is more effectively achieved with a combination of bNAbs. Here, we propose a computational approach to predict the efficacy of a bNAb therapy based on the population genetics of HIV escape, which we parametrize using high-throughput HIV sequence data from bNAb-naive patients. By quantifying the mutational target size and the fitness cost of HIV-1 escape from bNAbs, we predict the distribution of rebound times in three clinical trials. We show that a cocktail of three bNAbs is necessary to effectively suppress viral escape, and predict the optimal composition of such bNAb cocktail. Our results offer a rational therapy design for HIV, and show how genetic data can be used to predict treatment outcomes and design new approaches to pathogenic control.
Identifiants
pubmed: 35852143
doi: 10.7554/eLife.76004
pii: 76004
pmc: PMC9467514
doi:
pii:
Substances chimiques
Antibodies, Neutralizing
0
Broadly Neutralizing Antibodies
0
HIV Antibodies
0
Types de publication
Journal Article
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2022, LaMont et al.
Déclaration de conflit d'intérêts
CL, JO, KV, HG, FK No competing interests declared, AN Reviewing editor, eLife
Références
JCI Insight. 2019 Sep 5;4(17):
pubmed: 31484826
Elife. 2019 Dec 10;8:
pubmed: 31820734
Retrovirology. 2018 Nov 16;15(1):73
pubmed: 30445968
J Clin Invest. 2005 Nov;115(11):3250-5
pubmed: 16276421
Science. 2016 May 20;352(6288):1001-4
pubmed: 27199430
IEEE Trans Pattern Anal Mach Intell. 1984 Jun;6(6):721-41
pubmed: 22499653
Science. 2004 Nov 26;306(5701):1547-50
pubmed: 15567861
Proc Natl Acad Sci U S A. 1981 Jan;78(1):454-8
pubmed: 6165991
PLoS Genet. 2020 Oct 21;16(10):e1009009
pubmed: 33085662
J Antimicrob Chemother. 2003 Feb;51(2):229-40
pubmed: 12562686
J Virol. 2015 Mar;89(5):2659-71
pubmed: 25520506
Cell. 2020 Feb 6;180(3):471-489.e22
pubmed: 32004464
Proc Natl Acad Sci U S A. 2018 Jan 23;115(4):E564-E573
pubmed: 29311326
J Virol. 2008 Dec;82(24):12449-63
pubmed: 18842730
AIDS. 2001 Jun 15;15(9):F29-40
pubmed: 11416735
Nature. 2013 Apr 25;496(7446):441-2
pubmed: 23552894
Proc Natl Acad Sci U S A. 2021 Jul 27;118(30):
pubmed: 34301904
Nature. 2015 Jun 25;522(7557):487-91
pubmed: 25855300
Proc Natl Acad Sci U S A. 2000 Jul 5;97(14):7681-6
pubmed: 10884399
PLoS Pathog. 2020 Jun 3;16(6):e1008171
pubmed: 32492061
Nature. 2016 Jul 28;535(7613):556-60
pubmed: 27338952
Heredity (Edinb). 2008 Jan;100(1):19-31
pubmed: 17878920
Science. 2016 May 20;352(6288):997-1001
pubmed: 27199429
Proc Natl Acad Sci U S A. 2013 Oct 8;110(41):16538-43
pubmed: 24043801
Vaccine. 2016 Oct 26;34(45):5442-5448
pubmed: 27622299
Mol Biol Evol. 2019 Oct 1;36(10):2184-2194
pubmed: 31209469
AIDS Rev. 2006 Jul-Sep;8(3):125-40
pubmed: 17078483
Nat Rev Immunol. 2013 Sep;13(9):693-701
pubmed: 23969737
J Virol. 2001 Nov;75(22):10892-905
pubmed: 11602729
Cell. 2015 Jun 4;161(6):1280-92
pubmed: 26004070
Curr Opin Virol. 2019 Oct;38:21-30
pubmed: 31132749
Immunol Rev. 2017 Jan;275(1):313-323
pubmed: 28133794
Nature. 2013 Nov 14;503(7475):224-8
pubmed: 24172905
Genetics. 1988 Apr;118(4):705-11
pubmed: 17246421
Immunity. 2019 Feb 19;50(2):520-532.e3
pubmed: 30709739
PLoS Comput Biol. 2020 Feb 21;16(2):e1007626
pubmed: 32084132
PLoS Genet. 2016 Jul 21;12(7):e1006171
pubmed: 27442127
Elife. 2018 Mar 28;7:
pubmed: 29590010
Annu Rev Immunol. 2016 May 20;34:635-59
pubmed: 27168247
Bioinformatics. 2001 May;17(5):415-8
pubmed: 11331235
Science. 2009 Oct 9;326(5950):285-9
pubmed: 19729618
Immunity. 2013 Mar 21;38(3):606-17
pubmed: 23521886
AIDS. 2007 Mar 30;21(6):776-7
pubmed: 17413704
Bioessays. 2013 Jun;35(6):544-52
pubmed: 23613347
PLoS Comput Biol. 2022 Apr 6;18(4):e1010003
pubmed: 35385469
AIDS. 1999 Jul 30;13(11):F79-86
pubmed: 10449278
Science. 2012 Jul 13;337(6091):183-6
pubmed: 22798606
PLoS Comput Biol. 2020 Nov 30;16(11):e1008434
pubmed: 33253162
Curr Opin HIV AIDS. 2016 Jul;11(4):362-70
pubmed: 27259045
N Engl J Med. 2016 Nov 24;375(21):2019-2021
pubmed: 27959740
N Engl J Med. 2016 Nov 24;375(21):2037-2050
pubmed: 27959728
PLoS Pathog. 2017 May 25;13(5):e1006358
pubmed: 28542550
J Acquir Immune Defic Syndr. 2018 Oct 1;79(2):269-276
pubmed: 30211778
J Virol. 2017 Jul 27;91(16):
pubmed: 28539448
Science. 1996 Mar 15;271(5255):1582-6
pubmed: 8599114
Sci Transl Med. 2010 May 5;2(30):30ra32
pubmed: 20445200
Nature. 2013 Nov 14;503(7475):277-80
pubmed: 24172896
Elife. 2015 Dec 11;4:
pubmed: 26652000
Nat Med. 2021 Oct;27(10):1718-1724
pubmed: 34621054
PLoS Pathog. 2016 Mar 30;12(3):e1005520
pubmed: 27028935
Genet Res. 1966 Dec;8(3):269-94
pubmed: 5980116
Genetics. 2012 Oct;192(2):671-82
pubmed: 22851649
PLoS Pathog. 2011 Feb;7(2):e1001303
pubmed: 21383975
PLoS Genet. 2018 Jun 28;14(6):e1007420
pubmed: 29953449
Curr Opin Virol. 2012 Apr;2(2):134-41
pubmed: 22482710
Curr Opin HIV AIDS. 2017 May;12(3):229-240
pubmed: 28422787
J Bioinform Comput Biol. 2005 Feb;3(1):157-68
pubmed: 15751118
PLoS Comput Biol. 2010 Jan 29;6(1):e1000660
pubmed: 20126527
Science. 2013 Sep 13;341(6151):1199-204
pubmed: 24031012
J Virol. 2015 Apr;89(8):4201-13
pubmed: 25631091
Nat Rev Immunol. 2002 Jan;2(1):28-36
pubmed: 11905835
PLoS Pathog. 2018 Aug 20;14(8):e1007238
pubmed: 30125330
Front Immunol. 2021 Aug 31;12:710012
pubmed: 34531859
PLoS Pathog. 2018 Nov 5;14(11):e1007431
pubmed: 30395637
Nature. 2018 Sep;561(7724):479-484
pubmed: 30258136
Nat Med. 2018 Nov;24(11):1701-1707
pubmed: 30258217
Cell Host Microbe. 2017 Jun 14;21(6):777-787.e4
pubmed: 28579254
PLoS Genet. 2021 Jan 14;17(1):e1009050
pubmed: 33444376
Virus Evol. 2017 Mar 02;3(1):vex003
pubmed: 28458914
Elife. 2016 Feb 15;5:
pubmed: 26882502
Science. 2010 Aug 13;329(5993):811-7
pubmed: 20616231
J Virol. 2016 Jun 10;90(13):5899-5914
pubmed: 27053554
Nature. 2011 Sep 22;477(7365):466-70
pubmed: 21849977
Nat Med. 2017 Feb;23(2):185-191
pubmed: 28092665
Science. 2009 Nov 20;326(5956):1123-7
pubmed: 19965434
Nat Immunol. 2018 Nov;19(11):1179-1188
pubmed: 30333615
AIDS. 2000 Jul 28;14(11):1481-8
pubmed: 10983634
Nature. 2013 Apr 25;496(7446):469-76
pubmed: 23552890
Cell. 2014 Feb 13;156(4):633-48
pubmed: 24529371
J Clin Invest. 2020 Apr 1;130(4):1699-1712
pubmed: 31910162
Bull Math Biol. 2007 Aug;69(6):2027-60
pubmed: 17450401
J Infect Dis. 2012 May 15;205 Suppl 2:S241-9
pubmed: 22448022
Nature. 2012 Dec 6;492(7427):118-22
pubmed: 23103874