The Development of Artificial Neural Networks to Predict Virological response to Combination HIV Therapy
Why this work is in the frame
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Bibliographic record
Abstract
INTRODUCTION: When used in combination, antiretroviral drugs are highly effective for suppressing HIV replication. Nevertheless, treatment failure commonly occurs and is generally associated with viral drug resistance. The choice of an alternative regimen may be guided by a drug-resistance test. However, interpretation of resistance from genotypic data poses a major challenge. METHODS: As an alternative to current interpretation systems, we have developed artificial neural network (ANN) models to predict virological response to combination therapy from HIV genotype and other clinical information. RESULTS: ANN models trained with genotype, baseline viral load and time to follow-up viral load (1154 treatment change episodes from multiple clinics), produced predictions of virological response that were highly significantly correlated with actual responses (r2 = 0.53; P < 0.00001) using independent test data from clinics that contributed training data. Augmented models, trained with the additional variables of baseline CD4+ T-cell count and four treatment history variables, were more accurate, explaining 69% of the variance in virological response. Models trained with the full input dataset, but only those data involving highly active antiretroviral therapy (three or more full-dose antiretroviral drugs in combination), performed at an intermediate level, explaining 61% of the variance. The augmented models performed less well when tested with data from unfamiliar clinics that had not contributed data to the training dataset, explaining 46% of the variance in response. CONCLUSION: These data indicate that ANN models can be quite accurate predictors of virological response to HIV therapy even for patients from unfamiliar clinics. ANN models therefore warrant further development as a potential tool to aid treatment selection.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it