Early Initiation of Antiretroviral Therapy Following In Utero HIV Infection Is Associated With Low Viral Reservoirs but Other Factors Determine Viral Rebound.
Adult
Antiretroviral Therapy, Highly Active
/ methods
Female
HIV Infections
/ drug therapy
HIV-1
/ drug effects
Humans
Infant, Newborn
Infectious Disease Transmission, Vertical
/ prevention & control
Leukocytes, Mononuclear
/ virology
Polymerase Chain Reaction
Pregnancy
South Africa
Viral Load
/ drug effects
HIV reservoir
digital droplet PCR
early infant diagnosis
early treatment
in utero HIV
pediatric HIV
reservoir decay
viral rebound
Journal
The Journal of infectious diseases
ISSN: 1537-6613
Titre abrégé: J Infect Dis
Pays: United States
ID NLM: 0413675
Informations de publication
Date de publication:
01 12 2021
01 12 2021
Historique:
received:
24
11
2020
accepted:
29
04
2021
pubmed:
9
5
2021
medline:
3
2
2022
entrez:
8
5
2021
Statut:
ppublish
Résumé
Early HIV diagnosis allows combination antiretroviral therapy (cART) initiation in the first days of life following in utero (IU) infection. The impact of early cART initiation on infant viral reservoir size in the setting of high-frequency cART nonadherence is unknown. Peripheral blood total HIV DNA from 164 early treated (day 0-21 of life) IU HIV-infected South African infants was measured using droplet digital PCR at birth and following suppressive cART. We evaluated the impact of cART initiation timing on HIV reservoir size and decay, and on the risk of subsequent plasma viremia in cART-suppressed infants. Baseline HIV DNA (median 2.8 log10 copies/million peripheral blood mononuclear cells, range 0.7-4.8) did not correlate with age at cART initiation (0-21 days) but instead with maternal antenatal cART use. In 98 infants with plasma viral suppression on cART, HIV DNA half-life was 28 days. However, the probability of maintenance of plasma aviremia was low (0.46 at 12 months) and not influenced by HIV DNA load. Unexpectedly, longer time to viral suppression was associated with protection against subsequent viral rebound. With effective prophylaxis against mother-to-child transmission, cART initiation timing in the first 3 weeks of life is not critical to reservoir size.
Sections du résumé
BACKGROUND
Early HIV diagnosis allows combination antiretroviral therapy (cART) initiation in the first days of life following in utero (IU) infection. The impact of early cART initiation on infant viral reservoir size in the setting of high-frequency cART nonadherence is unknown.
METHODS
Peripheral blood total HIV DNA from 164 early treated (day 0-21 of life) IU HIV-infected South African infants was measured using droplet digital PCR at birth and following suppressive cART. We evaluated the impact of cART initiation timing on HIV reservoir size and decay, and on the risk of subsequent plasma viremia in cART-suppressed infants.
RESULTS
Baseline HIV DNA (median 2.8 log10 copies/million peripheral blood mononuclear cells, range 0.7-4.8) did not correlate with age at cART initiation (0-21 days) but instead with maternal antenatal cART use. In 98 infants with plasma viral suppression on cART, HIV DNA half-life was 28 days. However, the probability of maintenance of plasma aviremia was low (0.46 at 12 months) and not influenced by HIV DNA load. Unexpectedly, longer time to viral suppression was associated with protection against subsequent viral rebound.
CONCLUSIONS
With effective prophylaxis against mother-to-child transmission, cART initiation timing in the first 3 weeks of life is not critical to reservoir size.
Identifiants
pubmed: 33963757
pii: 6272368
doi: 10.1093/infdis/jiab223
pmc: PMC8643423
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1925-1934Subventions
Organisme : NIAID NIH HHS
ID : R01 AI133673
Pays : United States
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Wellcome Trust
ID : WT104748MA
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 110110/Z/15/Z
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 107752/Z/15/Z
Pays : United Kingdom
Informations de copyright
© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.
Références
J Immunol. 2009 Dec 1;183(11):7150-60
pubmed: 19917677
PLoS One. 2010 Apr 28;5(4):e10407
pubmed: 20442853
AIDS. 2008 Aug 20;22(13):1583-8
pubmed: 18670217
Clin Infect Dis. 2017 Jun 1;64(11):1471-1478
pubmed: 28329153
PLoS One. 2016 Apr 22;11(4):e0154391
pubmed: 27104621
Clin Infect Dis. 2015 Oct 1;61(7):1169-78
pubmed: 26063721
J Acquir Immune Defic Syndr. 2018 Oct 1;79(2):269-276
pubmed: 30211778
EBioMedicine. 2016 Sep;11:68-72
pubmed: 27460436
Blood. 2004 Feb 1;103(3):1030-2
pubmed: 14504106
J Clin Invest. 2018 Jul 2;128(7):3102-3115
pubmed: 29911997
J Int AIDS Soc. 2018 Aug;21(8):e25168
pubmed: 30094952
Lancet HIV. 2018 May;5(5):e250-e258
pubmed: 29739699
PLoS One. 2018 Oct 23;13(10):e0205579
pubmed: 30352067
Open Forum Infect Dis. 2017 Dec 09;5(1):ofx268
pubmed: 29354661
Nat Rev Immunol. 2016 Apr;16(4):259-71
pubmed: 26972723
Proc Natl Acad Sci U S A. 2016 Aug 2;113(31):8783-8
pubmed: 27432972
Lancet HIV. 2017 Oct;4(10):e442-e448
pubmed: 28711526
Clin Infect Dis. 2016 Dec 15;63(12):1645-1654
pubmed: 27660236
Antivir Ther. 2008;13(1):47-55
pubmed: 18389898
J Infect Dis. 2015 Jul 1;212(1):39-43
pubmed: 25538273
Pediatr Infect Dis J. 2019 Jul;38(7):e138-e142
pubmed: 31192977
EClinicalMedicine. 2020 May 08;22:100344
pubmed: 32510047
N Engl J Med. 2000 Oct 5;343(14):982-91
pubmed: 11018164
PLoS One. 2018 Apr 12;13(4):e0195514
pubmed: 29649264
BMC Infect Dis. 2016 Dec 9;16(1):742
pubmed: 27938348
AIDS. 2017 Aug 24;31(13):1847-1851
pubmed: 28609403
N Engl J Med. 2013 Nov 7;369(19):1828-35
pubmed: 24152233
Clin Infect Dis. 2020 Feb 14;70(5):859-866
pubmed: 30919879
J Clin Invest. 2017 Oct 2;127(10):3827-3834
pubmed: 28891813
J Acquir Immune Defic Syndr. 2010 Apr;53(5):553-63
pubmed: 20142750
Sci Transl Med. 2020 Mar 4;12(533):
pubmed: 32132218
PLoS One. 2017 Apr 17;12(4):e0175899
pubmed: 28414780
Nature. 2014 Aug 7;512(7512):74-7
pubmed: 25042999
J Int AIDS Soc. 2019 Aug;22(8):e25368
pubmed: 31441231
Lancet HIV. 2019 Jun;6(6):e373-e381
pubmed: 30987937
EClinicalMedicine. 2020 Jan 07;18:100241
pubmed: 31993578
J Acquir Immune Defic Syndr. 2017 Aug 15;75(5):554-560
pubmed: 28489732
AIDS. 2012 Jul 31;26(12):1483-90
pubmed: 22555165
J Infect Dis. 2014 Nov 15;210(10):1529-38
pubmed: 24850788
Clin Pharmacokinet. 2014 Nov;53(11):989-1004
pubmed: 25223699
Sci Transl Med. 2019 Nov 27;11(520):
pubmed: 31776292
Pediatr Infect Dis J. 2011 Nov;30(11):974-9
pubmed: 21734620
J Stat Softw. 2011 Mar;39(5):1-13
pubmed: 27065756
Stat Med. 1997 Feb 28;16(4):385-95
pubmed: 9044528
Am J Epidemiol. 1995 Dec 15;142(12):1330-7
pubmed: 7503054