Influence of dapivirine vaginal ring use on cervicovaginal immunity and functional microbiome in adolescent girls.
Journal
AIDS (London, England)
ISSN: 1473-5571
Titre abrégé: AIDS
Pays: England
ID NLM: 8710219
Informations de publication
Date de publication:
01 03 2021
01 03 2021
Historique:
pubmed:
13
11
2020
medline:
28
4
2021
entrez:
12
11
2020
Statut:
ppublish
Résumé
The antiretroviral-based dapivirine vaginal ring reduced HIV risk among women in phase III clinical trials. However, limited data exists on the impact of dapivirine on the vaginal microenvironment in adolescents. A comprehensive metaproteomics approach was used to assess host proteome and microbiome changes in cervicovaginal mucus with dapivirine ring use in adolescents enrolled in the MTN-023/IPM 030 (MTN-023) trial. Participants were randomized 3 : 1 to use dapivirine or placebo vaginal rings monthly for 6 months. Cervicovaginal samples from a subset of 35 participants (8 placebo, 27 dapivirine) were analyzed. Mass spectrometry analysis identified 405 human and 2467 bacterial proteins belonging to 15 unique genera. The host proteome belonged to many functional pathways primarily related to inflammation. When stratified by study treatment arm, 18 (4.4%) and 28 (6.9%) human proteins were differentially abundant (adjusted P < 0.05) between baseline and follow-up in the placebo and dapivirine arms, respectively. The vaginal microbiome was predominantly composed of Lactobacillus, Gardnerella, and Prevotella. Although bacterial taxa did not differ by arm or change significantly, Lactobacillus crispatus increased (P < 0.001) and Lactobacillus iners decreased (P < 0.001) during the 6-month follow-up. There were no significant differences in bacterial functions by arm or time in the trial. Protected vaginal sex significantly associated with decreased neutrophil inflammatory biomarkers and may be associated with changes in bacterial taxa and metabolism. Condom use may associate with differences to inflammation and bacterial function but dapivirine ring use does not, thereby supporting the mucosal safety profile of this vaginal ring for adolescents.
Identifiants
pubmed: 33181534
pii: 00002030-202103010-00003
doi: 10.1097/QAD.0000000000002751
pmc: PMC7924934
mid: NIHMS1656538
doi:
Substances chimiques
Anti-HIV Agents
0
Pyrimidines
0
Dapivirine
TCN4MG2VXS
Types de publication
Journal Article
Randomized Controlled Trial
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
369-380Subventions
Organisme : NICHD NIH HHS
ID : U01 HD040533
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI068615
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI068633
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI106707
Pays : United States
Informations de copyright
Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc.
Références
N Engl J Med. 2015 Feb 5;372(6):509-18
pubmed: 25651245
AIDS Res Hum Retroviruses. 2015 Nov;31(11):1139-52
pubmed: 26204200
PLoS One. 2019 Apr 4;14(4):e0213975
pubmed: 30947260
N Engl J Med. 2016 Dec;375(22):2121-2132
pubmed: 26900902
Int J Womens Health. 2013 Oct 21;5:695-708
pubmed: 24174884
PLoS One. 2012;7(7):e40415
pubmed: 22808157
J Infect Dis. 1999 Dec;180(6):1863-8
pubmed: 10558942
J Infect Dis. 2005 Oct 15;192(8):1372-80
pubmed: 16170754
mBio. 2015 Mar 24;6(2):
pubmed: 25805726
Microbiome. 2013 Dec 02;1(1):29
pubmed: 24451163
Lancet Infect Dis. 2018 Nov;18(11):1241-1250
pubmed: 30507409
PLoS One. 2012;7(2):e30633
pubmed: 22363457
J Clin Invest. 2011 Dec;121(12):4610-7
pubmed: 22133886
mBio. 2012 Dec 18;3(6):
pubmed: 23249810
Elife. 2015 Feb 03;4:
pubmed: 25647729
N Engl J Med. 2012 Aug 2;367(5):411-22
pubmed: 22784040
J Acquir Immune Defic Syndr. 2015 Nov 1;70(3):242-9
pubmed: 26034880
Sex Transm Infect. 2004 Feb;80(1):48-53
pubmed: 14755036
J Virol. 2015 Sep;89(17):8793-805
pubmed: 26085144
AIDS. 2011 May 15;25(8):1057-64
pubmed: 21505316
Trends Microbiol. 2017 Mar;25(3):182-191
pubmed: 27914761
Am J Reprod Immunol. 2015 Oct;74(4):323-32
pubmed: 26118476
Front Med (Lausanne). 2018 Jun 13;5:181
pubmed: 29951482
J Pediatr Adolesc Gynecol. 2009 Feb;22(1):11-8
pubmed: 19232297
J Acquir Immune Defic Syndr. 2015 Apr 15;68(5):495-501
pubmed: 25763783
J Acquir Immune Defic Syndr. 2008 Jun 1;48(2):203-10
pubmed: 18520679
J Adolesc Health. 2003 Mar;32(3):183-6
pubmed: 12606111
AIDS. 2014 Jun 19;28(10):1479-87
pubmed: 24901365
BMC Bioinformatics. 2010 Jul 02;11:367
pubmed: 20598126
mBio. 2019 Aug 13;10(4):
pubmed: 31409678
Obstet Gynecol. 2016 Jul;128(1):22-31
pubmed: 27275789
Sex Transm Infect. 2010 Aug;86(4):297-302
pubmed: 20660593
PLoS One. 2013;8(4):e60147
pubmed: 23573238
PLoS One. 2017 Feb 24;12(2):e0171856
pubmed: 28234976
PLoS One. 2018 Jul 23;13(7):e0201003
pubmed: 30036385
Am J Obstet Gynecol. 2013 Dec;209(6):505-23
pubmed: 23659989
PLoS One. 2014 Oct 21;9(10):e110980
pubmed: 25333937
AIDS Res Hum Retroviruses. 2016 Oct/Nov;32(10-11):1149-1158
pubmed: 27726428
J Reprod Immunol. 2011 Jan;88(1):66-71
pubmed: 21051089
Sex Transm Dis. 2004 Jul;31(7):393-400
pubmed: 15215693
Proc Natl Acad Sci U S A. 2011 Mar 15;108 Suppl 1:4680-7
pubmed: 20534435
Sex Transm Infect. 2018 Dec;94(8):616-618
pubmed: 29358524
J Infect Dis. 2009 Dec 1;200(11):1662-70
pubmed: 19863439
Science. 2017 Jun 2;356(6341):938-945
pubmed: 28572388
AIDS. 2000 Jan 7;14(1):85-8
pubmed: 10714571
N Engl J Med. 2016 Dec;375(22):2133-2143
pubmed: 27959766
Sci Rep. 2018 Jul 23;8(1):11109
pubmed: 30038262
Best Pract Res Clin Obstet Gynaecol. 2012 Aug;26(4):441-9
pubmed: 22429786
J Virol. 2013 May;87(9):5141-50
pubmed: 23449785
Sex Transm Dis. 2009 Jun;36(6):357-64
pubmed: 19434010
PLoS Med. 2012;9(6):e1001251
pubmed: 22745608
J Infect Dis. 2005 Feb 1;191(3):358-66
pubmed: 15633094
J Acquir Immune Defic Syndr. 2020 Feb 1;83(2):135-139
pubmed: 31929401
Obstet Gynecol. 2012 Dec;120(6):1306-13
pubmed: 23168754
N Engl J Med. 2008 Jul 31;359(5):463-72
pubmed: 18669425
Science. 2010 Sep 3;329(5996):1168-74
pubmed: 20643915
AIDS. 2001 Aug;15 Suppl 4:S51-60
pubmed: 11686466
Lancet. 2002 Sep 28;360(9338):971-7
pubmed: 12383665
AIDS. 1998 Sep 10;12(13):1699-706
pubmed: 9764791
PLoS Pathog. 2016 Sep 22;12(9):e1005889
pubmed: 27656899
Sci Rep. 2017 Sep 20;7(1):11974
pubmed: 28931859