Bayesian estimation of HIV acquisition dates for prevention trials
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Date
2025
Journal Title
Journal ISSN
Volume Title
Publisher
American Society for Microbiology
Abstract
Accurate timing estimates of when participants acquire HIV in HIV prevention trials are necessary for determining antibody levels at acquisition. The Antibody-Mediated Prevention (AMP) Studies showed that a passively administered broadly neutralizing antibody can prevent the acquisition of HIV from a neutralization-sensitive virus. We developed a pipeline for estimating the date of detectable HIV acquisition (DDA) in AMP Study participants using diagnostic and viral sequence data. Using a Bayesian strategy that combines three streams of data (REN [rev/vpu/env/Δnef] sequence, GP [gag/Δpol] sequence, and diagnostic) where their 95% credible intervals overlap based on pre-specified criteria and decision rules. We evaluated the performance of our AMP pipeline using PacBio viral sequence data from 41 participants across two prospective acute HIV acquisition cohort studies, FRESH and RV217, with twice-weekly sampling. These cohort studies enrolled young women in South Africa and men and women in Kenya and Thailand, respectively, with a high likelihood of HIV acquisition. In evaluating performance, “true DDA” was the center of bounds between last-negative and first-positive RNA diagnostic tests (median time 4 days, range 2–7 days); bias was the mean difference between estimated and true DDA. Using diagnostic data alone yielded timing estimates with a bias of 2.4 days and root mean square error (RMSE) of 7.9 days. These results were improved using sequence + diagnostic data (bias 1.5 days, RMSE 6.9 days), as well as by restricting sequence-based estimation to samples from ≤5 weeks post-DDA (bias 0.2 days, RMSE 7.8 days).
Description
Keywords
Acute Acquisition Cohort, Antibody-Mediated Prevention (Amp) Studies, Bayesian Posterior Distribution, Date Of Detectable Acquisition, Fresh
Citation
Rossenkhan, R., Giorgi, E.E., Shao, D., Ludwig, J., Labuschagne, P., Magaret, C.A., Ndung'u, T., Muema, D., Gounder, K., Dong, K.L. and Walker, B.D., 2025. Bayesian estimation of HIV acquisition dates for prevention trials. mBio, 16(10), pp.e01881-25.