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Title: Accidental Father-to-Son HIV-1 Transmission During the Seroconversion Period

Abstract

A 4-year-old child born to an HIV-1 seronegative mother was diagnosed with HIV-1, the main risk factor being transmission from the child's father who was seroconverting at the time of the child's birth. In the context of a forensic investigation, here we aimed to identify the source of infection of the child and date of the transmission event. Samples were collected from the father and child at two time points about 4 years after the child's birth. Partial segments of three HIV-1 genes (gag, pol, and env) were sequenced and maximum likelihood (ML) and Bayesian methods were used to determine direction and estimate date of transmission. Neutralizing antibodies were determined using a single cycle assay. Bayesian trees displayed a paraphyletic–monophyletic topology in all three genomic regions, with the father's host label at the root, which is consistent with father-to-son transmission. ML trees found similar topologies in gag and pol and a monophyletic–monophyletic topology in env. Analysis of the time of the most recent common ancestor of each HIV-1 gene population indicated that the child was infected shortly after the father. Consistent with the infection history, both father and son developed broad and potent HIV-specific neutralizing antibody responses. In conclusion, themore » direction of transmission implicated the father as the source of transmission. Transmission occurred during the seroconversion period when the father was unaware of the infection and was likely accidental. This case shows how genetic, phylogenetic, and serological data can contribute for the forensic investigation of HIV transmission.« less

Authors:
 [1];  [2];  [2];  [3];  [4]; ORCiD logo [5]; ORCiD logo [5];  [1]
  1. Univ. of Lisbon (Portugal); Inst. Univ. Egas Moniz (IUEM), Monte de Caparica (Portugal)
  2. Univ. of Lisbon (Portugal)
  3. NOVA Univ., Lisbon (Portugal)
  4. Hospital Fernando Fonseca, Amadors (Portugal)
  5. Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
Publication Date:
Research Org.:
Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
Sponsoring Org.:
USDOE Laboratory Directed Research and Development (LDRD) Program; National Institutes of Health (NIH); European Funds; Fundacao para a Ciencia e Tecnologia (FCT), Portugal
OSTI Identifier:
1634956
Report Number(s):
LA-UR-19-25850
Journal ID: ISSN 0889-2229
Grant/Contract Number:  
89233218CNA000001; R01AI087520; 249697; PTDC/SAU-EPI/122400/2010; VIH/SAU/0029/2011; PTDC/DTP-EPI/7066/2014; UID/Multi/04413/2013; SFRH/BPD/76225/2011
Resource Type:
Accepted Manuscript
Journal Name:
AIDS Research and Human Retroviruses
Additional Journal Information:
Journal Volume: 34; Journal Issue: 10; Journal ID: ISSN 0889-2229
Country of Publication:
United States
Language:
English
Subject:
biological science; HIV father-to-son transmission; forensic investigation of HIV transmission; phylogenetic analysis; neutralizing antibodies

Citation Formats

Ezeonwumelu, Ifeanyi, Bártolo, Inês, Martin, Francisco, Abecasis, Ana, Campos, Teresa, Romero-Severson, Ethan O., Leitner, Thomas, and Taveira, Nuno. Accidental Father-to-Son HIV-1 Transmission During the Seroconversion Period. United States: N. p., 2018. Web. doi:10.1089/aid.2018.0060.
Ezeonwumelu, Ifeanyi, Bártolo, Inês, Martin, Francisco, Abecasis, Ana, Campos, Teresa, Romero-Severson, Ethan O., Leitner, Thomas, & Taveira, Nuno. Accidental Father-to-Son HIV-1 Transmission During the Seroconversion Period. United States. doi:10.1089/aid.2018.0060.
Ezeonwumelu, Ifeanyi, Bártolo, Inês, Martin, Francisco, Abecasis, Ana, Campos, Teresa, Romero-Severson, Ethan O., Leitner, Thomas, and Taveira, Nuno. Thu . "Accidental Father-to-Son HIV-1 Transmission During the Seroconversion Period". United States. doi:10.1089/aid.2018.0060. https://www.osti.gov/servlets/purl/1634956.
@article{osti_1634956,
title = {Accidental Father-to-Son HIV-1 Transmission During the Seroconversion Period},
author = {Ezeonwumelu, Ifeanyi and Bártolo, Inês and Martin, Francisco and Abecasis, Ana and Campos, Teresa and Romero-Severson, Ethan O. and Leitner, Thomas and Taveira, Nuno},
abstractNote = {A 4-year-old child born to an HIV-1 seronegative mother was diagnosed with HIV-1, the main risk factor being transmission from the child's father who was seroconverting at the time of the child's birth. In the context of a forensic investigation, here we aimed to identify the source of infection of the child and date of the transmission event. Samples were collected from the father and child at two time points about 4 years after the child's birth. Partial segments of three HIV-1 genes (gag, pol, and env) were sequenced and maximum likelihood (ML) and Bayesian methods were used to determine direction and estimate date of transmission. Neutralizing antibodies were determined using a single cycle assay. Bayesian trees displayed a paraphyletic–monophyletic topology in all three genomic regions, with the father's host label at the root, which is consistent with father-to-son transmission. ML trees found similar topologies in gag and pol and a monophyletic–monophyletic topology in env. Analysis of the time of the most recent common ancestor of each HIV-1 gene population indicated that the child was infected shortly after the father. Consistent with the infection history, both father and son developed broad and potent HIV-specific neutralizing antibody responses. In conclusion, the direction of transmission implicated the father as the source of transmission. Transmission occurred during the seroconversion period when the father was unaware of the infection and was likely accidental. This case shows how genetic, phylogenetic, and serological data can contribute for the forensic investigation of HIV transmission.},
doi = {10.1089/aid.2018.0060},
journal = {AIDS Research and Human Retroviruses},
number = 10,
volume = 34,
place = {United States},
year = {2018},
month = {9}
}

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