Title
Genital shedding of human immunodeficiency virus Type-1 (HIV) when antiretroviral therapy suppresses HIV replication in the plasma
Date Issued
01 September 2020
Access level
open access
Resource Type
journal article
Author(s)
Bull M.
Mitchell C.
Styrchak S.
Williams C.
Dragavon J.
Ryan K.J.
Acosta E.
Onchiri F.
Coombs R.W.
Frenkel L.M.
Publisher(s)
Oxford University Press
Abstract
Background. During antiretroviral treatment (ART) with plasma HIV RNA below the limit of quantification, HIV RNA can be detected in genital or rectal secretions, termed discordant shedding (DS). We hypothesized that proliferating cells produce virions without HIV replication. Methods. ART-naive Peruvians initiating ART were observed for DS over 2 years. HIV env and pol genomes were amplified from DS. Antiretrovirals and cytokines/chemokines concentrations were compared at DS and control time points. Results. Eighty-two participants had ART suppression. DS was detected in 24/82 (29%) participants: 13/253 (5%) cervicovaginal lavages, 20/322 (6%) seminal plasmas, and 6/85 (7%) rectal secretions. HIV RNA in DS specimens was near the limit of quantification and not reproducible. HIV DNA was detected in 6/13 (46%) DS cervicovaginal lavages at low levels. Following DNase treatment, 5/39 DS specimens yielded HIV sequences, all without increased genetic distances. Women with and without DS had similar plasma antiretroviral levels and DS in 1 woman was associated with inflammation. Conclusions. HIV RNA and DNA sequences and therapeutic antiretroviral plasma levels did not support HIV replication as the cause of DS from the genital tract. Rather, our findings infer that HIV RNA is shed due to proliferation of infected cells with virion production.
Start page
777
End page
786
Volume
222
Issue
5
Language
English
OCDE Knowledge area
Enfermedades infecciosas
Subjects
Scopus EID
2-s2.0-85089128102
PubMed ID
Source
Journal of Infectious Diseases
ISSN of the container
00221899
Sponsor(s)
Funding text
This work was supported by the National Institute of Allergy and Infectious Disease (grant numbers R01 AI071212 and R01 AI091550 to L. M. F.); and the University of Washington Center for AIDS Research (grant numbers P30 AI027757, AI068636, and AI106701 to K. Holmes).
Sources of information:
Directorio de Producción Científica
Scopus