PrEP Adherence Patterns Strongly Affect Individual HIV Risk and Observed Efficacy in Randomized Clinical Trials
Bibliographic record
Abstract
BACKGROUND: Randomized controlled trials (RCTs) suggest that the efficacy of tenofovir-based preexposure prophylaxis (PrEP) strongly depends on the consistency of PrEP use. We explore how the patterns of pill taking and waning of PrEP protection may affect PrEP efficacy for HIV prevention. METHODS: A 2-arm RCT was simulated by mathematical models assuming that the prescribed daily doses were skipped periodically, randomly, or in large blocks. Risk-driven adherence, in which PrEP was taken when sex was expected, was also investigated. Three temporal PrEP protection profiles were explored: long (5 days), intermediate (3 days), and short (24 hours). Modeling results were compared to the efficacy observed in completed RCTs. RESULTS: The expected PrEP efficacy was 60% with periodic, 50% with random, and 34% with block adherence when PrEP had a long protection profile and pills were taken only 50% of the days. Risk-driven pill taking resulted in 29% and 37% daily pills taken and efficacy of 43% and 51%, respectively, for long protection. High PrEP efficacy comparable with that observed in Partners PrEP and Centers for Disease Control and Prevention Botswana trials was simulated under long protection, high overall adherence, and limited block pill taking; the moderate efficacy observed in iPrEx and Bangkok trials was comparable with the 50% adherence scenarios under random pill taking and long protection. CONCLUSIONS: Pill-taking patterns may have a substantial impact on the protection provided by PrEP even when the same numbers of pills are taken. When PrEP retains protection for longer than a day, pill-taking patterns can explain a broad range of efficacies observed in PrEP RCTs.
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How this classification was reachedexpand
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 | 0.040 | 0.068 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.003 | 0.002 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.001 |
| 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 itClassification
machine, unvalidatedMachine predicted; both teacher heads agree on what is shown here.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".