| Title: |
Bayesian estimation of HIV acquisition dates for prevention trials |
| Authors: |
Rossenkhan, Raabya; Giorgi, Elena E; Shao, Danica; Ludwig, James; Labuschagne, Phillip; Magaret, Craig A; Ndung'u, Thumbi; Muema, Daniel; Gounder, Kamini; Dong, Krista L; Walker, Bruce D; Rolland, Morgane; Robb, Merlin L; Eller, Leigh Anne; Sawe, Fredrick; Nitayaphan, Sorachai; Grebe, Eduard; Busch, Michael P; Delaney, Kevin P; Facente, Shelley; Carpp, Lindsay N; deCamp, Allan C; Huang, Yunda; Korber, Bette; Juraska, Michal; Rudnicki, Erika; Kosmider, Ewelina; Reeves, Daniel B; Mayer, Bryan T; Hural, John; Deng, Wenjie; Westfall, Dylan H; Yssel, Anna; Matten, David; Bhattacharya, Tanmoy; Corey, Lawrence; Gilbert, Peter B; Williamson, Carolyn; Mullins, James I; Edlefsen, Paul T |
| Contributors: |
Mahalingam, Suresh |
| Source: |
mBio, vol 16, iss 10 |
| Publisher Information: |
eScholarship, University of California |
| Publication Year: |
2025 |
| Collection: |
University of California: eScholarship |
| Subject Terms: |
3207 Medical Microbiology (for-2020); 32 Biomedical and Clinical Sciences (for-2020); 3204 Immunology (for-2020); Infectious Diseases (rcdc); Vaccine Related (rcdc); Women's Health (rcdc); Clinical Research (rcdc); Immunization (rcdc); HIV/AIDS (rcdc); Prevention (rcdc); Clinical Trials and Supportive Activities (rcdc); Vaccine Related (AIDS) (rcdc); Sexually Transmitted Infections (rcdc); Infection (hrcs-hc); 3 Good Health and Well Being (sdg); Humans (mesh); HIV Infections (mesh); Bayes Theorem (mesh); Male (mesh); Female (mesh); Time Factors (mesh); South Africa (mesh); HIV Antibodies (mesh); Kenya (mesh); HIV-1 (mesh); Adult (mesh); Young Adult (mesh); Thailand (mesh); Prospective Studies (mesh); acute acquisition cohort |
| Subject Geographic: |
e01881 - e01825 |
| Description: |
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).IMPORTANCEIn HIV prevention trials, accurate timing estimates of when individual participants acquire HIV can be used to estimate antibody levels at the time of acquisition, which is useful for projecting antibody levels needed for prevention. The results we report here suggest that if sequence-based estimation of acquisition timing is used in future clinical trials of combination broadly neutralizing ... |
| Document Type: |
article in journal/newspaper |
| Language: |
unknown |
| Relation: |
qt25z6r80r; https://escholarship.org/uc/item/25z6r80r |
| DOI: |
10.1128/mbio.01881-25 |
| Availability: |
https://escholarship.org/uc/item/25z6r80r; https://doi.org/10.1128/mbio.01881-25 |
| Rights: |
CC-BY |
| Accession Number: |
edsbas.119E214B |
| Database: |
BASE |