Higher colorectal tissue HIV infectivity in cisgender women compared with MSM before and during oral preexposure prophylaxis.
Journal
AIDS (London, England)
ISSN: 1473-5571
Titre abrégé: AIDS
Pays: England
ID NLM: 8710219
Informations de publication
Date de publication:
01 08 2021
01 08 2021
Historique:
pubmed:
9
4
2021
medline:
7
8
2021
entrez:
8
4
2021
Statut:
ppublish
Résumé
The objective of this study was to compare HIV-negative cisgender women (CGW) with MSM for mucosal tissue differences in pharmacokinetics, HIV infectivity and cell phenotype. A substudy of HPTN 069/ACTG A5305, 48-week study of three oral candidate preexposure prophylaxis regimens: maraviroc, maraviroc/emtricitabine and maraviroc/tenofovir disoproxil fumarate (TDF) compared with a TDF/emtricitabine control group. Plasma, peripheral blood mononuclear cells and cervical and colorectal tissue biopsies were collected at Baseline (no drug), Week 24 and 48 (on drug), and Week 49 (1-week postdrug). Drug concentrations were assessed in all matrices. HIV infectivity was assessed using tissue biopsy 'explants' challenged with HIV ex vivo followed by HIV p24 measurement. Flow cytometry evaluated colorectal cell phenotype. Thirty-seven CGW and 54 MSM participated. CGW's colorectal explant p24 was higher than MSM before (0.31 log10, P = 0.046), during (1.01-1.19 log10, P = 0.016) and one week after (0.61 log10, P = 0.011) study drug dosing. Pooling regimens, cervical explant p24 did not differ among visits. CGW had higher plasma maraviroc and colorectal tissue tenofovir diphosphate and lower colorectal tissue emtricitabine (all P < 0.005) compared with MSM. Each study drug's cervical tissue concentrations were more than 10-fold below paired colorectal concentrations (P < 0.001). Cell phenotype sex differences included 4% higher CD38+/CD8+ cells at baseline and 3-7% higher CD69+/CD8+ cells throughout Weeks 24-49 in CGW compared with MSM (P < 0.05). Colorectal explants in CGW demonstrated greater HIV infectivity than MSM with and without study drugs. Small differences in adherence, drug concentration and colorectal tissue flow cytometry cannot fully explain this difference.
Identifiants
pubmed: 33831911
doi: 10.1097/QAD.0000000000002907
pii: 00002030-202108010-00007
pmc: PMC8483241
mid: NIHMS1690139
doi:
Substances chimiques
Anti-HIV Agents
0
Emtricitabine
G70B4ETF4S
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1585-1595Subventions
Organisme : NIAID NIH HHS
ID : UM1 AI069494
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000005
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI068633
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI069534
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI106707
Pays : United States
Organisme : NIAID NIH HHS
ID : U01 AI068617
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI068619
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI069419
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI069424
Pays : United States
Organisme : NCRR NIH HHS
ID : UL1 RR024153
Pays : United States
Organisme : NIAID NIH HHS
ID : P30 AI045008
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI068634
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI069465
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI068613
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI068636
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI068617
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.
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