Evidence map›Paper›PMID 27558421›Full record

Trial reportJournal of virology2016

HIV-1-Neutralizing IgA Detected in Genital Secretions of Highly HIV-1-Exposed Seronegative Women on Oral Preexposure Prophylaxis.

Jennifer M Lund, Kristina Broliden, Maria N Pyra, Katherine K Thomas, Deborah Donnell, Elizabeth Irungu, Timothy R Muwonge, Nelly Mugo, Madhuri Manohar, Marianne Jansson and 4 more

Erratum issued Registry-linked trialOpen access · bronzeAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Journal of virology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT03701802 (Immunogenetic Modulators of Mucosal Protection From HIV-1), which is not on this map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.4field-weighted citation impact, top 18% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT03701802 completednot on this mapstarted 2018, after this paper: background citation

Immunogenetic Modulators of Mucosal Protection From HIV-1: The Kinga Study

TypeobservationalSponsorUniversity of WashingtonRan2018 to 2020Enrolled812ConditionsHIV Infections, HSV-2 Infection
3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 11 citations in OpenAlex.

  1. Trial
  2. Article
  3. Article
  4. Review
  5. Review
  6. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 6 institutions in 4 countries.

Jennifer M LundVaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA Department of Global Health, University of Washington, Seattle, Washington, USA jlund@fredhutch.org.ORCID http://orcid.org/0000-0003-3284-979X
Kristina BrolidenDepartment of Medicine, Karolinska Institute, Stockholm, Sweden.
Maria N PyraDepartment of Global Health, University of Washington, Seattle, Washington, USA.
Katherine K ThomasDepartment of Global Health, University of Washington, Seattle, Washington, USA.
Deborah DonnellVaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA Department of Global Health, University of Washington, Seattle, Washington, USA.
Elizabeth IrunguPartners in Health Research and Development, Kenya Medical Research Institute, Thika, Kenya.
Timothy R MuwongeInfectious Disease Institute, Makerere University, Kampala, Uganda.
Nelly MugoPartners in Health Research and Development, Kenya Medical Research Institute, Thika, Kenya.
Madhuri ManoharDepartment of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Marianne JanssonDepartment of Laboratory Medicine, Lund University, Lund, Sweden.
Romel MackelprangDepartment of Global Health, University of Washington, Seattle, Washington, USA.
Mark A MarzinkeDepartment of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Jared M BaetenDepartment of Global Health, University of Washington, Seattle, Washington, USA Department of Medicine, University of Washington, Seattle, Washington, USA Department of Epidemiology, University of Washington, Seattle, Washington, USA.
Jairam R LingappaDepartment of Global Health, University of Washington, Seattle, Washington, USA Department of Medicine, University of Washington, Seattle, Washington, USA Department of Pediatrics, University of Washington, Seattle, Washington, USA.
University of Washington · USJohns Hopkins University · USKenya Medical Research Institute · KEKarolinska Institutet · SELund University · SEMakerere University · UG

Funding

PrEP and protective immune responses against HIV-1R01AI096968 · NIAID · UNIVERSITY OF WASHINGTON · PI BAETEN, JARED, LUND, JENNIFER M · 2012 to 2015
$2.8M
NIAID NIH HHS R01 AI096968
6 · The paper itself

Abstract

Although nonhuman primate studies have shown that simian immunodeficiency virus/simian-human immunodeficiency virus (SIV/SHIV) exposure during preexposure prophylaxis (PrEP) with oral tenofovir can induce SIV immunity without productive infection, this has not been documented in humans. We evaluated cervicovaginal IgA in Partners PrEP Study participants using a subtype C primary isolate and found that women on PrEP had IgA with higher average human immunodeficiency virus type 1 (HIV-1)-neutralizing magnitude than women on placebo (33% versus 7%; P = 0.008). Using a cutoff of ≥90% HIV-1 neutralization, 19% of women on-PrEP had HIV-1-neutralizing IgA compared to 0% of women on placebo (P = 0.09). We also estimated HIV-1 exposure and found that the proportion of women with HIV-1-neutralizing IgA was associated with the level of HIV-1 exposure (P = 0.04). Taken together, our data suggest that PrEP and high levels of exposure to HIV may each enhance mucosal HIV-1-specific humoral immune responses in sexually exposed but HIV-1-uninfected individuals. IMPORTANCE: Although there is not yet an effective HIV-1 vaccine, PrEP for at-risk HIV-1-uninfected individuals is a highly efficacious intervention to prevent HIV-1 acquisition and is currently being recommended by the CDC and WHO for all individuals at high risk of HIV-1 acquisition. We previously demonstrated that PrEP use does not enhance peripheral blood HIV-1-specific T-cell responses in HIV-exposed individuals. Here, we evaluate for cervicovaginal HIV-neutralizing IgA responses in genital mucosal secretions of HIV-exposed women, which is likely a more relevant site than peripheral blood for observation of potentially protective immune events occurring in response to sexual HIV-1 exposure for various periods. Furthermore, we assess for host response in the context of longitudinal quantification of HIV-1 exposure. We report that HIV-neutralizing IgA is significantly correlated with higher HIV-1 exposure and, furthermore, that there are more women with HIV-1-neutralizing IgA in the on-PrEP group than in the placebo group.

Indexed as

AdultAntibodies, NeutralizingFemaleHIV-1HIV InfectionsHumansImmunoglobulin ALongitudinal StudiesPre-Exposure ProphylaxisSexual BehaviorAntibodies, NeutralizingImmunoglobulin A

Identifiers

PMID27558421
PMCPMC5068535
OpenAlexW2513987945

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.