Journal Article

Molecular dating and viral load growth rates suggested that the eclipse phase lasted about a week in HIV-1 infected adults in East Africa and Thailand

Li, Yifan, Nitayaphan, Sorachai, Ahani, Bahar, Kim, Jerome H., Owen, Christopher L., Dearlove, Bethany, Labuschagne, Jan Phillipus Lourens, Pham, Phuc, Rossenkhan, Raabya, Robb, Merlin L., Reeves, Daniel B., Edlefsen, Paul T., Kijak, Gustavo, Eller, Leigh Anne, Gramzinski, Robert, Lewitus, Eric, Sanders-Buell, Eric, Bonar, Lydia, Maganga, Lucas, Michael, Nelson L., Tovanabutra, Sodsai, Poltavee, Kultida, Kibuuka, Hannah, Miller, Shana, Rolland, Morgane, O’Sullivan, AnneMarie, Bose, Meera, Harbolick, Elizabeth, Lee, Jenica, Sawe, Fred K.

2020

Overview

Most HIV-1 infected individuals do not know their infection dates. Precise infection timing is crucial information for studies that document transmission networks or drug levels at infection. To improve infection timing, we used the prospective RV217 cohort where the window when plasma viremia becomes detectable is narrow: the last negative visit occurred a median of four days before the first detectable HIV-1 viremia with an RNA test, referred below as diagnosis. We sequenced 1,280 HIV-1 genomes from 39 participants at a median of 4, 32 and 170 days post-diagnosis. HIV-1 infections were dated by using sequence-based methods and a viral load regression method. Bayesian coalescent and viral load regression estimated that infections occurred a median of 6 days prior to diagnosis (IQR: 9-3 and 11-4 days prior, respectively). Poisson-Fitter, which analyzes the distribution of hamming distances among sequences, estimated a median of 7 days prior to diagnosis (IQR: 15-4 days) based on sequences sampled 4 days post-diagnosis, but it did not yield plausible results using sequences sampled at 32 days. Fourteen participants reported a high-risk exposure event at a median of 8 days prior to diagnosis (IQR: 12 to 6 days prior). These different methods concurred that HIV-1 infection occurred about a week before detectable viremia, corresponding to 20 days (IQR: 34-15 days) before peak viral load. Together, our methods comparison helps define a framework for future dating studies in early HIV-1 infection.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adult / Africa, Eastern / Analysis / Armed forces / Bayesian analysis / Biology and Life Sciences / Cancer / Computer and Information Sciences / Dating / Diagnosis / Female / Funding / Genome, Viral / Genomes / Genomics / Growth rate / Health aspects / HIV / HIV Infections - diagnosis / HIV Infections - genetics / HIV-1 - genetics / HIV-1 - metabolism / Human immunodeficiency virus / Humans / Infection / Infections / Infectious diseases / Load distribution / Male / Medical research / Medicine / Medicine and Health Sciences / Military medicine / Molecular Diagnostic Techniques / Peak load / Physical Sciences / Prospective Studies / Regression analysis / Research and Analysis Methods / Ribonucleic acid / RNA / Thailand / Time Factors / Vaccines / Viral Load / Viremia / Viremia - diagnosis / Viremia - genetics