DOE OSTI · 2998258
Bayesian estimation of HIV acquisition dates for prevention trials
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).
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Rossenkhan, Raabya [Fred Hutchinson Cancer Center, Seattle, WA (United States)] (ORCID:0009000559078325), Giorgi, Elena E. [Fred Hutchinson Cancer Center, Seattle, WA (United States)], Shao, Danica [Fred Hutchinson Cancer Center, Seattle, WA (United States)], Ludwig, James [Fred Hutchinson Cancer Center, Seattle, WA (United States)], Labuschagne, Phillip [Fred Hutchinson Cancer Center, Seattle, WA (United States); Univ. of the Western Cape, Cape Town (South Africa)], Magaret, Craig A. [Fred Hutchinson Cancer Center, Seattle, WA (United States)], Ndung'u, Thumbi [Univ. of KwaZulu-Natal, Durban (South Africa); Africa Health Research Inst. (AHRI), Durban (South Africa); Univ. College London (United Kingdom); Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States); Harvard Univ., Cambridge, MA (United States)], Muema, Daniel [Univ. of KwaZulu-Natal, Durban (South Africa); Africa Health Research Inst. (AHRI), Durban (South Africa)], Gounder, Kamini [Univ. of KwaZulu-Natal, Durban (South Africa); Africa Health Research Inst. (AHRI), Durban (South Africa)], Dong, Krista L. [Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States); Harvard Univ., Cambridge, MA (United States)], Walker, Bruce D. [Univ. of KwaZulu-Natal, Durban (South Africa); Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States); Harvard Univ., Cambridge, MA (United States); Howard Hughes Medical Inst., Chevy Chase, MD (United States)], Rolland, Morgane [Walter Reed Army Institute of Research, Silver Spring, MD (United States); Henry M. Jackson Foundation for the Advancement of Military Medicine (HJF), Bethesda, MD (United States)] (ORCID:0000000336508490), Robb, Merlin L. [Henry M. Jackson Foundation for the Advancement of Military Medicine (HJF), Bethesda, MD (United States)], Eller, Leigh Anne [Walter Reed Army Institute of Research, Silver Spring, MD (United States); Henry M. Jackson Foundation for the Advancement of Military Medicine (HJF), Bethesda, MD (United States)], Sawe, Fredrick [Henry Jackson Foundation Medical Research International (HJFMRI), Nairobi (Kenya); U.S. Army Medical Research Directorate, Nairobi (Kenya)], Nitayaphan, Sorachai [Armed Forces Research Institute of Medical Sciences (AFRIMS), Bangkok (Thailand)], Grebe, Eduard [Stellenbosch Univ. (South Africa); Univ. of California, San Francisco, CA (United States)] (ORCID:0000000170467245), Busch, Michael P. [Univ. of California, San Francisco, CA (United States); Vitalant Research Inst., San Francisco, CA (United States) ], Delaney, Kevin P. [Centers for Disease Control and Prevention (CDC), Atlanta, GA (United States). National Center for HIV, Viral Hepatitis, STD, and Tuberculosis Prevention (NCHHSTP)], Facente, Shelley [Vitalant Research Inst., San Francisco, CA (United States); Facente Consulting, Richmond, VA (United States); Univ. of California, Berkeley, CA (United States)], Carpp, Lindsay N. [Fred Hutchinson Cancer Center, Seattle, WA (United States)] (ORCID:0000000303335925), deCamp, Allan C. [Fred Hutchinson Cancer Center, Seattle, WA (United States)], Huang, Yunda [Fred Hutchinson Cancer Center, Seattle, WA (United States); Univ. of Washington, Seattle, WA (United States)], Korber, Bette [New Mexico Consortium, Los Alamos, NM (United States); Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)], Juraska, Michal [Fred Hutchinson Cancer Center, Seattle, WA (United States)], Rudnicki, Erika [Fred Hutchinson Cancer Center, Seattle, WA (United States)], Kosmider, Ewelina [Fred Hutchinson Cancer Center, Seattle, WA (United States)], Reeves, Daniel B. [Fred Hutchinson Cancer Center, Seattle, WA (United States); Univ. of Washington, Seattle, WA (United States)] (ORCID:0000000156849538), Mayer, Bryan T. [Fred Hutchinson Cancer Center, Seattle, WA (United States)], Hural, John [Fred Hutchinson Cancer Center, Seattle, WA (United States)], Deng, Wenjie [Univ. of Washington, Seattle, WA (United States)], Westfall, Dylan H. [Univ. of Washington, Seattle, WA (United States)], Yssel, Anna [Univ. of Cape Town (South Africa)], Matten, David [Univ. of Cape Town (South Africa)], Bhattacharya, Tanmoy [New Mexico Consortium, Los Alamos, NM (United States); Santa Fe Inst. (SFI), Santa Fe, NM (United States)] (ORCID:000000021060652X), Corey, Lawrence Tina Marie [Fred Hutchinson Cancer Center, Seattle, WA (United States); Univ. of Washington, Seattle, WA (United States)] (ORCID:0000000220265757), Gilbert, Peter B. [Fred Hutchinson Cancer Center, Seattle, WA (United States); Univ. of Washington, Seattle, WA (United States)], Williamson, Carolyn [Univ. of Cape Town (South Africa)] (ORCID:0000000301251226), Mullins, James I. [Univ. of Washington, Seattle, WA (United States)], Edlefsen, Paul T. [Fred Hutchinson Cancer Center, Seattle, WA (United States)] (ORCID:0000000283938103). 2025-09-09. Bayesian estimation of HIV acquisition dates for prevention trials. https://doi.org/10.1128/mbio.01881-25
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