Factors influencing estimates of HIV-1 infection timing using BEAST.
Bethany L DearloveSodsai TovanabutraChristopher L OwenEric LewitusYifan LiEric Sanders-BuellMeera BoseAnne-Marie O'SullivanGustavo H KijakShana MillerKultida PoltaveeJenica LeeLydia BonarElizabeth HarbolickBahar AhaniPhuc PhamHannah KibuukaLucas MagangaSorachai NitayaphanFred K SaweJerome H KimLeigh Anne EllerSandhya VasanRobert A GramzinskiNelson L MichaelMerlin L RobbMorgane Rollandnull nullPublished in: PLoS computational biology (2021)
While large datasets of HIV-1 sequences are increasingly being generated, many studies rely on a single gene or fragment of the genome and few comparative studies across genes have been done. We performed genome-based and gene-specific Bayesian phylogenetic analyses to investigate how certain factors impact estimates of the infection dates in an acute HIV-1 infection cohort, RV217. In this cohort, HIV-1 diagnosis corresponded to the first RNA positive test and occurred a median of four days after the last negative test, allowing us to compare timing estimates using BEAST to a narrow window of infection. We analyzed HIV-1 sequences sampled one week, one month and six months after HIV-1 diagnosis in 39 individuals. We found that shared diversity and temporal signal was limited in acute infection, and insufficient to allow timing inferences in the shortest HIV-1 genes, thus dated phylogenies were primarily analyzed for env, gag, pol and near full-length genomes. There was no one best-fitting model across participants and genes, though relaxed molecular clocks (73% of best-fitting models) and the Bayesian skyline (49%) tended to be favored. For infections with single founders, the infection date was estimated to be around one week pre-diagnosis for env (IQR: 3-9 days) and gag (IQR: 5-9 days), whilst the genome placed it at a median of 10 days (IQR: 4-19). Multiply-founded infections proved problematic to date. Our ability to compare timing inferences to precise estimates of HIV-1 infection (within a week) highlights that molecular dating methods can be applied to within-host datasets from early infection. Nonetheless, our results also suggest caution when using uniform clock and population models or short genes with limited information content.
Keyphrases
- antiretroviral therapy
- genome wide
- hiv infected
- hiv positive
- human immunodeficiency virus
- hiv testing
- hiv aids
- genome wide identification
- hepatitis c virus
- men who have sex with men
- liver failure
- dna methylation
- mycobacterium tuberculosis
- randomized controlled trial
- genome wide analysis
- healthcare
- drug induced
- health information
- respiratory failure
- clinical trial
- hepatitis b virus
- bioinformatics analysis
- single cell
- extracorporeal membrane oxygenation
- genetic diversity
- case control