Estimating the timing of mother-to-child transmission of the human immunodeficiency virus type 1 using a viral molecular evolution model.
BACKGROUND
Mother-to-child transmission (MTCT) is responsible for most pediatric HIV-1 infections worldwide. It can occur during pregnancy, labor, or breastfeeding. Numerous studies have used coalescent and molecular clock methods to understand the epidemic history of HIV-1, but the timing of vertical transmission has not been studied using these methods. Taking advantage of the constant accumulation of HIV genetic variation over time and using longitudinally sampled viral sequences, we used a coalescent approach to investigate the timing of MTCT.


METHODS
Six-hundred and twenty-two clonal env sequences from the RNA and DNA viral population were longitudinally sampled from nine HIV-1 infected mother-and-child pairs [range: 277-1034 days]. For each transmission pair, timing of MTCT was determined using a coalescent-based model within a Bayesian statistical framework. Results were compared with available estimates of MTCT timing obtained with the classic biomedical approach based on serial HIV DNA detection by PCR assays.


RESULTS
Four children were infected during pregnancy, whereas the remaining five children were infected at time of delivery. For eight out of nine pairs, results were consistent with the transmission periods assessed by standard PCR-based assay. The discordance in the remaining case was likely confused by co-infection, with simultaneous introduction of multiple maternal viral variants at the time of delivery.


CONCLUSIONS
The study provided the opportunity to validate the Bayesian coalescent approach that determines the timing of MTCT of HIV-1. It illustrates the power of population genetics approaches to reliably estimate the timing of transmission events and deepens our knowledge about the dynamics of viral evolution in HIV-infected children, accounting for the complexity of multiple transmission events.
Université François-Rabelais, Institut National de la Santé et de la Recherche Médicale - Unité 966 et Laboratoire de Virologie, Centre Hopsitalier Universitaire Bretonneau, Tours, France; University of California San Diego, Department of Pathology, San Diego, California, United States of America.
Antoine
A
Chaillon
Université François-Rabelais, Institut National de la Santé et de la Recherche Médicale - Unité 966 et Laboratoire de Virologie, Centre Hopsitalier Universitaire Bretonneau, Tours, France; Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand.
Tanawan
T
Samleerat
Laboratoire Ecologie et Evolution, Centre National de la Recherche Scientifique - Unité Mixte de Recherche 7625- Ecole Normale Supérieure, Paris, France.
Faustine
F
Zoveda
Laboratoire Ecologie et Evolution, Centre National de la Recherche Scientifique - Unité Mixte de Recherche 7625- Ecole Normale Supérieure, Paris, France.
Sébastien
S
Ballesteros
Université François-Rabelais, Institut National de la Santé et de la Recherche Médicale - Unité 966 et Laboratoire de Virologie, Centre Hopsitalier Universitaire Bretonneau, Tours, France.
Alain
A
Moreau
Institut de Recherche pour le Développement, Chiang Mai, Thailand; Harvard School of Public Health, Department of Immunology and Infectious Diseases, Boston, Massachusetts, United States of America.
Nicole
N
Ngo-Giang-Huong
Institut de Recherche pour le Développement, Chiang Mai, Thailand; Harvard School of Public Health, Department of Immunology and Infectious Diseases, Boston, Massachusetts, United States of America.
Gonzague
G
Jourdain
University of California San Diego, Department of Pathology, San Diego, California, United States of America.
Sara
S
Gianella
Institut de Recherche pour le Développement, Chiang Mai, Thailand; Harvard School of Public Health, Department of Immunology and Infectious Diseases, Boston, Massachusetts, United States of America.
Marc
M
Lallemant
Laboratoire Ecologie et Evolution, Centre National de la Recherche Scientifique - Unité Mixte de Recherche 7625- Ecole Normale Supérieure, Paris, France.
Frantz
F
Depaulis
Université François-Rabelais, Institut National de la Santé et de la Recherche Médicale - Unité 966 et Laboratoire de Virologie, Centre Hopsitalier Universitaire Bretonneau, Tours, France.
Francis
F
Barin
D001499:Bayes Theorem; D002648:Child; D019020:Directed Molecular Evolution; D005260:Female; D015497:HIV-1 / Q000235:genetics* / Q000502:physiology*; D006801:Humans; D018445:Infectious Disease Transmission, Vertical; D008390:Markov Chains; D008954:Models, Biological; D009010:Monte Carlo Method; D010802:Phylogeny; D011247:Pregnancy; D017422:Sequence Analysis, DNA; D013997:Time Factors