Dataset Information

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 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.

SUBMITTER: Rolland M

PROVIDER: S-EPMC7004303 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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.

Rolland Morgane M Tovanabutra Sodsai S Dearlove Bethany B Li Yifan Y Owen Christopher L CL Lewitus Eric E Sanders-Buell Eric E Bose Meera M O'Sullivan AnneMarie A Rossenkhan Raabya R Labuschagne Jan Phillipus Lourens JPL Edlefsen Paul T PT Reeves Daniel B DB Kijak Gustavo G Miller Shana S Poltavee Kultida K Lee Jenica J Bonar Lydia L Harbolick Elizabeth E Ahani Bahar B Pham Phuc P Kibuuka Hannah H Maganga Lucas L Nitayaphan Sorachai S Sawe Fred K FK Eller Leigh Anne LA Gramzinski Robert R Kim Jerome H JH Michael Nelson L NL Robb Merlin L ML

PLoS pathogens 20200206 2

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 genome ...[more]

PMID: 32027734

Similar Datasets

Project description:BackgroundAcute human immunodeficiency virus type 1 (HIV-1) infection is a major contributor to transmission of HIV-1. An understanding of acute HIV-1 infection may be important in the development of treatment strategies to eradicate HIV-1 or achieve a functional cure.MethodsWe performed twice-weekly qualitative plasma HIV-1 RNA nucleic acid testing in 2276 volunteers who were at high risk for HIV-1 infection. For participants in whom acute HIV-1 infection was detected, clinical observations, quantitative measurements of plasma HIV-1 RNA levels (to assess viremia) and HIV antibodies, and results of immunophenotyping of lymphocytes were obtained twice weekly.ResultsFifty of 112 volunteers with acute HIV-1 infection had two or more blood samples collected before HIV-1 antibodies were detected. The median peak viremia (6.7 log10 copies per milliliter) occurred 13 days after the first sample showed reactivity on nucleic acid testing. Reactivity on an enzyme immunoassay occurred at a median of 14 days. The nadir of viremia (4.3 log10 copies per milliliter) occurred at a median of 31 days and was nearly equivalent to the viral-load set point, the steady-state viremia that persists durably after resolution of acute viremia (median plasma HIV-1 RNA level, 4.4 log10 copies per milliliter). The peak viremia and downslope were correlated with the viral-load set point. Clinical manifestations of acute HIV-1 infection were most common just before and at the time of peak viremia. A median of one symptom of acute HIV-1 infection was recorded at a median of two study visits, and a median of one sign of acute HIV-1 infection was recorded at a median of three visits.ConclusionsThe viral-load set point occurred at a median of 31 days after the first detection of plasma viremia and correlated with peak viremia. Few symptoms and signs were observed during acute HIV-1 infection, and they were most common before peak viremia. (Funded by the Department of Defense and the National Institute of Allergy and Infectious Diseases.).

Project description:BackgroundExcessive impact peak forces and vertical load rates are associated with running injuries and have been targeted in gait retraining studies. This study aimed to determine the effects of 12-week cadence retraining on impact peak, vertical load rates and lower extremity biomechanics during running.MethodsTwenty-four healthy male recreational runners were randomised into either a 12-week cadence retraining group (n = 12), which included those who ran with a 7.5% increase in preferred cadence, or a control group (n = 12), which included those who ran without any changes in cadence. Kinematics and ground reaction forces were recorded simultaneously to quantify impact force variables and lower extremity kinematics and kinetics.ResultsSignificantly decreased impact peak (1.86 ± 0.30 BW vs. 1.67 ± 0.27 BW, P = 0.003), vertical average load rates (91.59 ± 18.91 BW/s vs. 77.31 ± 15.12 BW/s, P = 0.001) and vertical instantaneous load rates (108.8 ± 24.5 BW/s vs. 92.8 ± 18.5 BW/s, P = 0.001) were observed in the cadence retraining group, while no significant differences were observed in the control group. Foot angles (18.27° ± 5.59° vs. 13.74° ± 2.82°, P = 0.003) and vertical velocities of the centre of gravity (CoG) (0.706 ± 0.115 m/s vs. 0.652 ± 0.091 m/s, P = 0.002) significantly decreased in the cadence retraining group at initial contact, but not in the control group. In addition, vertical excursions of the CoG (0.077 ± 0.01 m vs. 0.069 ± 0.008 m, P = 0.002) and peak knee flexion angles (38.6° ± 5.0° vs. 36.5° ± 5.5°, P < 0.001) significantly decreased whilst lower extremity stiffness significantly increased (34.34 ± 7.08 kN/m vs. 38.61 ± 6.51 kN/m, P = 0.048) in the cadence retraining group. However, no significant differences were observed for those variables in the control group.ConclusionTwelve-week cadence retraining significantly increased the cadence of the cadence retraining group by 5.7%. This increased cadence effectively reduced impact peak and vertical average/instantaneous load rates. Given the close relationship between impact force variables and running injuries, increasing the cadence as a retraining method may potentially reduce the risk of impact-related running injuries.

Project description:ObjectiveEngagement in care is key to successful HIV treatment in resource-limited settings; yet little is known about the magnitude and determinants of reengagement among patients out of care. We assessed patient-reported reasons for not returning to clinic, identified latent variables underlying these reasons, and examined their influence on subsequent care reengagement.DesignWe used data from the East Africa International Epidemiologic Databases to Evaluate AIDS to identify a cohort of patients disengaged from care (>3 months late for last appointment, reporting no HIV care in preceding 3 months) (n = 430) who were interviewed about reasons why they stopped care. Among the 399 patients for whom follow-up data were available, 104 returned to clinic within a median observation time of 273 days (interquartile range: 165-325).MethodsWe conducted exploratory and confirmatory factor analyses (EFA, CFA) to identify latent variables underlying patient-reported reasons, then used these factors as predictors of time to clinic return in adjusted Cox regression models.ResultsEFA and CFA findings suggested a six-factor structure that lent coherence to the range of barriers and motivations underlying care disengagement, including poverty, transport costs, and interference with work responsibilities; health system 'failures,' including poor treatment by providers; fearing disclosure of HIV status; feeling healthy; and treatment fatigue/seeking spiritual alternatives to medicine. Factors related to poverty and poor treatment predicted higher rate of return to clinic, whereas the treatment fatigue factor was suggestive of a reduced rate of return.ConclusionCertain barriers to reengagement appear easier to overcome than factors such as treatment fatigue. Further research will be needed to identify the easiest, least expensive interventions to reengage patients lost to HIV care systems. Interpersonal interventions may continue to play an important role in addressing psychological barriers to retention.

Project description:BackgroundUpdated World Health Organization guidelines have amplified debate about how resource constraints should impact monitoring strategies for HIV-infected persons on combination antiretroviral therapy (cART). We estimated the incremental benefit and cost effectiveness of alternative monitoring strategies for east Africans with known HIV infection.MethodsUsing a validated HIV computer simulation based on resource-limited data (USAID and AMPATH) and circumstances (east Africa), we compared alternative monitoring strategies for HIV-infected persons newly started on cART. We evaluated clinical, immunologic and virologic monitoring strategies, including combinations and conditional logic (e.g., only perform virologic testing if immunologic testing is positive). We calculated incremental cost-effectiveness ratios (ICER) in units of cost per quality-adjusted life year (QALY), using a societal perspective and a lifetime horizon. Costs were measured in 2008 US dollars, and costs and benefits were discounted at 3%. We compared the ICER of monitoring strategies with those of other resource-constrained decisions, in particular earlier cART initiation (at CD4 counts of 350 cells/mm3 rather than 200 cells/mm3).ResultsMonitoring strategies employing routine CD4 testing without virologic testing never maximized health benefits, regardless of budget or societal willingness to pay for additional health benefits. Monitoring strategies employing virologic testing conditional upon particular CD4 results delivered the most benefit at willingness-to-pay levels similar to the cost of earlier cART initiation (approximately $2600/QALY). Monitoring strategies employing routine virologic testing alone only maximized health benefits at willingness-to-pay levels (> $4400/QALY) that greatly exceeded the ICER of earlier cART initiation.ConclusionsCD4 testing alone never maximized health benefits regardless of resource limitations. Programmes routinely performing virologic testing but deferring cART initiation may increase health benefits by reallocating monitoring resources towards earlier cART initiation.

Dataset Information

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.

Publications

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.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets