Two companion papers — one conceptual framework, one computational validation — built the scientific foundation for a clinical decision support tool that navigates the 2–8 week structural vulnerability between LAI-PrEP prescription and first injection, where 47.1% of patients are currently lost.
Long-acting injectable PrEP (LAI-PrEP) offers over 96% efficacy in HIV prevention — superior to every oral formulation studied. Yet a structural failure in healthcare delivery erases that advantage before it begins.
Not because the medication fails. Because the healthcare system does. The 2–8 week "bridge period" between prescription and first injection — required for mandatory HIV testing, insurance authorization, and appointment coordination — creates a structural vulnerability unique to LAI-PrEP. The pharmacological constraint cannot be eliminated for new starts; it can only be systematically managed. That is what this tool does.
Paradoxically, patients who survive the bridge period show 81–83% persistence — far exceeding oral PrEP's 52%. The bottleneck is not retention. It is initiation.
The tool is the product of a deliberate research architecture: one paper to define the problem and build the evidence library, one paper to prove the solution works at global scale.
Defines the bridge period as a distinct, measurable cascade step. Synthesizes data from HPTN 083, HPTN 084, PURPOSE-1/2 (>15,000 participants) with real-world implementation cohorts. Characterizes 13 structural barriers across 7 population categories. Builds the 21-intervention evidence library with mechanism classification, effect sizes, and evidence tier ratings across 6 supplementary files. This is the intellectual architecture the tool required to function.
Validates the clinical decision support tool across 21.2 million synthetic patients — the UNAIDS 2025 global PrEP target — achieving policy-grade statistical precision (±0.018 pp). Progressive validation at 1K, 1M, 10M, and 21.2M scales. 18/18 edge cases passing. Demonstrates the tool's mathematical architecture — multiplicative barrier compounding, mechanism diversity scoring — functions correctly at any scale from a single clinic to global deployment.
A Python-based, configuration-driven clinical decision support tool that synthesizes the evidence from both companion papers into patient-level guidance. The tool stratifies individual bridge period risk, identifies the specific structural barriers affecting each patient, and recommends evidence-based interventions prioritized by expected impact — with mechanism diversity scoring to prevent redundant recommendations.
The tool operationalizes a three-mechanism framework for bridge period management, drawing on the 21-intervention evidence library synthesized in Paper I and validated computationally in Paper II.
Oral-to-injectable same-day switching for the 3.8 million patients already on oral PrEP. Existing negative test results and established clinical engagement remove the bridge period entirely. The highest single-impact intervention identified — +35% absolute improvement. The tool prioritizes this pathway whenever patient history permits.
Dual HIV testing (antigen/antibody + RNA) shortens the mandatory window period from 45 days to 10–14 days. Point-of-care RNA platforms enable same-visit testing. The tool selects accelerated diagnostic pathways for patients where same-day switching is not feasible, compressing the structural vulnerability window to its minimum safe duration.
Dedicated patient navigation, transportation support, telehealth integration, and harm reduction co-location for patients facing multiple co-occurring barriers. Patients with 3+ structural barriers face less than 15% baseline probability. The tool's mechanism diversity scoring ensures navigation interventions address distinct barrier types rather than duplicating effort.
The tool's most important finding: populations with the lowest baseline bridge period success rates show the greatest relative improvement with targeted interventions. Systematic implementation narrows health equity gaps rather than widening them.
At UNAIDS 2025 target scale: 4.1 million additional successful transitions, 100,000 HIV infections prevented annually, $40 billion in averted lifetime treatment costs. 11:1 five-year return on investment.
The tool is freely available to healthcare providers, researchers, and public health agencies. Pharmaceutical entities require written permission for commercial use.
Conflict of interest: Dr. Demidont was formerly employed by Gilead Sciences (ending October 2024); all holdings divested December 2024. This research received no industry funding. Disclosed per ICMJE guidelines in all publications.