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

Abstract

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 sequencebased 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.

TLR7 agonist, N6-LS and PGT121 delayed viral rebound in SHIV-infected macaques after antiretroviral therapy interruption

“…In this study, ART was initiated 14 days post SHIV inoculation. The MHRP RV217 prospective cohort involving seronegative high-risk individuals who underwent twice-weekly HIV-1 RNA testing estimated the eclipse phase (the time between HIV-1 infection and a diagnosable infection by nucleic acid testing) to be a week [ 22 ]. Thus ART initiation at day 14 more closely mirrors what is feasible in HIV-infected individuals, including our current clinical RV254 cohort in Thailand, where individuals are diagnosed and initiated on ART at the earliest stages of HIV infection [ 23 ].…”

Estimation of the incubation period of COVID-19 using viral load data

“…Estimating the incubation period is challenging, because we rarely directly observe the time of infection or the time of symptom onset (examples to the contrary in HIV infection show the intense follow-up needed to observe these events ( Robb et al, 2016 ; Rolland et al, 2020 )). The first study estimating the incubation period of SARS-CoV-2 was that of Li et al ( Bi et al, 2020 ), who fit a log-normal model to a subset of cases for whom detailed information about exposure to another case was available.…”

New SHIVs and Improved Design Strategy for Modeling HIV-1 Transmission, Immunopathogenesis, Prevention, and Cure

“…The CE1176 Env is from a widely used global test panel for bNAb detection (41). Env RV217.40100 is a new subtype AE T/F strain (48,49) and Envs CH1012 and CH0694 are T/F strains that elicited potent bNAbs in their respective human hosts (50,51 The design strategy for constructing SHIVs is illustrated in Fig. 1A.…”