Evidence map›Paper›PMID 33798244›Full record

ArticlePLoS pathogens2021

Mutations that confer resistance to broadly-neutralizing antibodies define HIV-1 variants of transmitting mothers from that of non-transmitting mothers.

Amit Kumar, Elena E Giorgi, Joshua J Tu, David R Martinez, Joshua Eudailey, Michael Mengual, Manukumar Honnayakanahalli Marichannegowda, Russell Van Dyke, Feng Gao, Sallie R Permar

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.0field-weighted citation impact, top 27% 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 8 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 4 institutions in 1 country.

Amit KumarDuke Human Vaccine Institute, Duke University Medical Centre, Durham, North Carolina, United States of America.
Elena E GiorgiLos Alamos National Laboratory, Los Alamos, New Mexico, United States of America.
Joshua J TuDuke Human Vaccine Institute, Duke University Medical Centre, Durham, North Carolina, United States of America.ORCID 0000-0001-9391-3375
David R MartinezDuke Human Vaccine Institute, Duke University Medical Centre, Durham, North Carolina, United States of America.
Joshua EudaileyDuke Human Vaccine Institute, Duke University Medical Centre, Durham, North Carolina, United States of America.ORCID 0000-0002-1731-9806
Michael MengualDepartment of Medicine, Duke University Medical Centre, Durham, North Carolina, United States of America.
Manukumar Honnayakanahalli MarichannegowdaDepartment of Medicine, Duke University Medical Centre, Durham, North Carolina, United States of America.ORCID 0000-0002-6488-7136
Russell Van DykeTulane University School of Medicine, New Orleans, Louisiana, United States of America.
Feng GaoDepartment of Medicine, Duke University Medical Centre, Durham, North Carolina, United States of America.ORCID 0000-0001-8903-0203
Sallie R PermarDuke Human Vaccine Institute, Duke University Medical Centre, Durham, North Carolina, United States of America.ORCID 0000-0003-1438-4554
Duke Medical Center · USCornell University · USLos Alamos National Laboratory · USTulane University · US

Funding

PHACS - Data and Operations CenterU01HD052102 · NICHD · HARVARD UNIVERSITY (SCH OF PUBLIC HLTH) · PI WILLIAMS, PAIGE L · 2005 to 2019
$242.7M
Virus biology scientific research support componentUM1AI100645 · NIAID · DUKE UNIVERSITY · PI HAHN, BEATRICE H · 2012 to 2018
$204.7M
Pediatric HIV/AIDS Cohort Study (PHACS): Understanding Maternal HIV Disease through Pregnancy and the Postpartum Period and its Role in Child Health OutcomesU01HD052104 · NICHD · TULANE UNIVERSITY OF LOUISIANA · PI VAN DYKE, RUSSELL B. · 2005 to 2019
$15.7M
Escape of maternal plasma broadly neutralizing antibody as a mechanism of mother to child HIV transmissionR01AI162245 · NIAID · WEILL MEDICAL COLL OF CORNELL UNIV · PI PERMAR, SALLIE R. · 2021 to 2024
$3.2M
Role of neutralizing antibodies in HIV-1-infected and vaccinated mothers in MTCTR01AI122909 · NIAID · DUKE UNIVERSITY · PI KUMAR, AMIT · 2016 to 2019
$2.6M
NIAID NIH HHS R01 AI122909NIAID NIH HHS R01 AI162245NIAID NIH HHS UM1 AI100645NICHD NIH HHS U01 HD052102NICHD NIH HHS U01 HD052104
6 · The paper itself

Abstract

Despite considerable reduction of mother-to-child transmission (MTCT) of HIV through use of maternal and infant antiretroviral therapy (ART), over 150,000 infants continue to become infected with HIV annually, falling far short of the World Health Organization goal of reaching <20,000 annual pediatric HIV cases worldwide by 2020. Prior to the widespread use of ART in the setting of pregnancy, over half of infants born to HIV-infected mothers were protected against HIV acquisition. Yet, the role of maternal immune factors in this protection against vertical transmission is still unclear, hampering the development of synergistic strategies to further reduce MTCT. It has been established that infant transmitted/founder (T/F) viruses are often resistant to maternal plasma, yet it is unknown if the neutralization resistance profile of circulating viruses predicts the maternal risk of transmission to her infant. In this study, we amplified HIV-1 envelope genes (env) by single genome amplification and produced representative Env variants from plasma of 19 non-transmitting mothers from the U.S. Women Infant Transmission Study (WITS), enrolled in the pre-ART era. Maternal HIV Env variants from non-transmitting mothers had similar sensitivity to autologous plasma as observed for non-transmitting variants from transmitting mothers. In contrast, infant variants were on average 30% less sensitive to paired plasma neutralization compared to non-transmitted maternal variants from both transmitting and non-transmitting mothers (p = 0.015). Importantly, a signature sequence analysis revealed that motifs enriched in env sequences from transmitting mothers were associated with broadly neutralizing antibody (bnAb) resistance. Altogether, our findings suggest that circulating maternal virus resistance to bnAb-mediated neutralization, but not autologous plasma neutralization, near the time of delivery, predicts increased MTCT risk. These results caution that enhancement of maternal plasma neutralization through passive or active vaccination during pregnancy may potentially drive the evolution of variants fit for vertical transmission.

Indexed as

Genetic VariationInfectious Disease Transmission, VerticalBroadly Neutralizing Antibodiesenv Gene Products, Human Immunodeficiency VirusFemaleHIV-1HIV AntibodiesHIV InfectionsHumansInfantMothersPhylogenyPregnancyBroadly Neutralizing Antibodiesenv Gene Products, Human Immunodeficiency VirusHIV Antibodies

Identifiers

PMID33798244
PMCPMC8055002
OpenAlexW3212285141

What OpenQuestion holds

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Registered trials

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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 OpenQuestion graph.