Genital shedding of human immunodeficiency virus Type-1 (HIV) when antiretroviral therapy suppresses HIV replication in the plasma

Marta Bull, Caroline Mitchell, Jaime Soria, Sheila Styrchak, Corey Williams, Joan Dragavon, Kevin J. Ryan, Edward Acosta, Frankline Onchiri, Robert W. Coombs, Alberto la Rosa, Eduardo Ticona, Lisa M. Frenkel

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

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.

Original languageEnglish
Pages (from-to)777-786
Number of pages10
JournalJournal of Infectious Diseases
Volume222
Issue number5
DOIs
StatePublished - 1 Sep 2020

Bibliographical note

Funding Information:
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).

Publisher Copyright:
© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Keywords

  • Drug levels
  • Genital HIV shedding
  • HIV phylogenetics
  • Inflammation

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