PROJECT VIRELATE-PRISM™ (PRISM-ΔHIV) | SCF TIER → FDA-APPROVED / PRE-APPROVED DRUG MAPPING

Document Code: SCF-VIR-AIDSΔ-FDA-MAP-001

Scope: HIV, AIDS-like viragenic syndromes, Tier I–V viral pathology

Regulatory Intent: IND bridging, 505(b)(2) repurposing logic, adjunctive combination design

TIER I — TRANSIENT IMMUNE / METABOLIC PERTURBATION

SCF Fault Class: Cytokine drift, reversible Δψm instability

Therapeutic Role: Preventative / Stabilization

FDA-Approved Drug	Primary MoA	SCF Target Node	Regulatory Status
N‑Acetylcysteine	Glutathione precursor	Redox collapse prevention	Approved
Metformin	AMPK activation	ATP/cAMP stabilization	Approved
Atorvastatin	Anti-inflammatory pleiotropy	Immune tone normalization	Approved

SCF Interpretation:

Tier I does not require antiviral suppression. FDA-approved metabolic stabilizers fully satisfy SCF Preventative PCR mode.

TIER II — SYSTEMIC INFLAMMATORY LOAD / METABOLIC STRAIN

SCF Fault Class: Chronic cytokine activation, early stromal stress

Therapeutic Role: Preventative → Early Curative

FDA-Approved Drug	Primary MoA	SCF Target Node	Regulatory Status
Tofacitinib	JAK-STAT inhibition	Cytokine drift suppression	Approved
Baricitinib	IL-6/IFN modulation	Immune circuit damping	Approved
Sirolimus	mTOR inhibition	Metabolic-immune recalibration	Approved

SCF Interpretation:

Tier II drugs act upstream of viral identity, stabilizing host terrain before Tier III escalation.

TIER III — ECM / LYMPHOID MICROENVIRONMENT INJURY

SCF Fault Class: ECM scaffold decay, thymic stress, immune desynchronization

Therapeutic Role: Curative (Structural)

FDA-Approved Drug	Primary MoA	SCF Target Node	Regulatory Status
Pirfenidone	TGF-β suppression	ECM fibrosis control	Approved
Nintedanib	VEGF/FGF/PDGF blockade	Stromal preservation	Approved
Sargramostim	Myeloid/immune regeneration	Lymphoid support	Approved

SCF Interpretation:

Tier III is where AIDS-mimetic pathology begins. Antivirals alone are insufficient; ECM-active FDA drugs are mandatory.

TIER IV — EPIGENOMIC DRIFT / PRE-COLLAPSE

SCF Fault Class: Partial lineage identity loss, TRECs decline

Therapeutic Role: Curative + Early Restorative

FDA-Approved / Late-Stage Drug	Primary MoA	SCF Target Node	Status
Decitabine	DNA hypomethylation	Epigenomic reactivation	Approved
Azacitidine	DNMT inhibition	Lineage identity repair	Approved
Romidepsin	Chromatin remodeling	Latent immune reset	Approved

SCF Interpretation:

Tier IV requires epigenomic tools already FDA-approved, but used at non-oncologic, SCF-tuned dosing.

TIER V — AIDS-CLASS (HIV-EXCLUSIVE)

SCF Fault Class: Irreversible CD4 lineage collapse without intervention

Therapeutic Role: Full SCF-PCR Braid (Preventative + Curative + Restorative)

CORE ANTIVIRAL (PREVENTATIVE / CURATIVE)

FDA-Approved Regimen	SCF Role
Biktarvy	Viral suppression (Preventative)
Dolutegravir	High-barrier resistance control
Tenofovir alafenamide	Targeted intracellular delivery

RESTORATIVE / LINEAGE SUPPORT (ADJUNCTIVE)

FDA-Approved Drug	SCF Role
IL‑7 (CYT107)	Thymic regeneration
Maraviroc	Immune microenvironment normalization
Lenalidomide	Immune circuit re-synchronization

SCF Interpretation:

ART prevents death, but does not restore immune identity.

Only FDA-approved epigenomic + regenerative adjuncts complete Tier V therapy.

REGULATORY TRANSLATION SUMMARY

SCF Tier	FDA Pathway Strategy
Tier I–II	Direct label use / off-label standard of care
Tier III	505(b)(2) repurposing (ECM-centric)
Tier IV	IND-bridged epigenomic adjuncts
Tier V	Combination IND (ART + regenerative adjunct)

SCF-PCR OPTIMIZED DOSING MATRICES

PROJECT VIRELATE-AIDS Δ

Preventative → Curative → Restorative (PCR) Sequencing

Document Code: SCF-VIR-AIDSΔ-PCR-DOSE-001

Applies To: Adult & Pediatric protocols (age-stratified matrices embedded)

Regulatory Use: IND Module 2.7 / 5, DSMB review, physician education

I. SCF-PCR DOSING PHILOSOPHY (CORE)

Traditional HIV dosing is drug-centric.

SCF-PCR dosing is system-centric.

Principle	SCF Interpretation
Dose	A signal, not a blunt force
Duration	Tier-dependent, not lifelong
Sequencing	Mandatory (P → C → R)
Escalation	Biomarker-gated
De-escalation	Default after resolution

II. PCR-PHASE DOSING OVERVIEWv (HIGH LEVEL)

PCR Phase	Objective	Dosing Character
Preventative (P)	Terrain stabilization	Low–moderate, continuous or pulsed
Curative (C)	Structural & identity correction	Time-limited, intensive
Restorative (R)	Immune lineage rebuilding	Pulsed, regenerative

III. TIER I — PREVENTATIVE DOSING MATRIX

Transient Immune / Metabolic Perturbation

PCR Role: Preventative

Clinical Goal: Stop Tier II escalation before antiviral dependence

Drug	Exposure Target	Duration	Key Biomarkers
N-Acetylcysteine	Redox normalization (GSH↑)	2–8 weeks	GSH/GSSG, ROS
Metformin	AMPK activation without lactate drift	4–12 weeks	Lactate, ATP/cAMP
Atorvastatin	CRP/IL-6 reduction	8–24 weeks	CRP, IL-6

SCF Rule:

Tier I agents may continue into Tier II, but never escalate dose unless biomarkers worsen.

IV. TIER II — PREVENTATIVE → EARLY CURATIVE DOSING MATRIX

Systemic Inflammatory Load / Metabolic Strain

PCR Role: Preventative → Curative

Clinical Goal: Interrupt cytokine-driven immune drift

Drug	Exposure Logic	Duration	Stop Criteria
Tofacitinib	Low-range JAK occupancy	4–8 weeks	IL-6 normalization
Baricitinib	IL-6/IFN damping	4–8 weeks	IFN-γ ↓
Sirolimus	Low trough, metabolic reset	8–16 weeks	mTOR tone normalized

Non-Negotiable Safety Locks:

ANC
Infection surveillance
Growth/thymic output (pediatrics)

SCF Insight:

Tier II is never chronic in SCF logic.

V. TIER III — CURATIVE DOSING MATRIX

ECM / Lymphoid Microenvironment Injury

PCR Role: Curative (Structural)

Clinical Goal: Repair immune architecture ART cannot fix

Drug	Dosing Strategy	Duration	Success Signal
Pirfenidone	Anti-fibrotic steady exposure	12–24 weeks	Fibrosis markers ↓
Nintedanib	Low-intensity stromal blockade	12–24 weeks	VEGF/FGF tone ↓
Sargramostim	Pulsed regenerative dosing	6–12 weeks	CD4 trafficking ↑

SCF Rule:

Tier III must precede Tier IV.

Skipping Tier III predicts epigenomic failure.

VI. TIER IV — CURATIVE → EARLY RESTORATIVE DOSING MATRIX

Epigenomic Drift / Pre-Collapse

PCR Role: Curative + Early Restorative

Clinical Goal: Restore immune lineage identity

Drug	SCF-Optimized Exposure	Cycle Design	Recovery Gate
Decitabine	Micro-dose hypomethylation	1–2 short cycles	Marrow recovery
Azacitidine	Signal-level DNMT inhibition	1–3 cycles	TRECs ↑
Romidepsin	Chromatin reset (restricted)	Single cycle	Exhaustion markers ↓

Critical SCF Rule:

These are identity signals, not oncologic cytotoxics.

VII. TIER V — FULL PCR BRAID DOSING MATRIX

AIDS-Class (HIV-Exclusive)

A. Preventative / Curative (ART Backbone)

Agent	Dosing Logic	Duration
Biktarvy®	Standard suppressive dosing	Until reservoir control
Dolutegravir	High-barrier integrase lock	Continuous initially
Tenofovir alafenamide	Intracellular targeting	Continuous initially

B. Restorative / Lineage Support (Adjunctive)

Agent	Dosing Pattern	Duration
IL-7 (CYT107)	Pulsed regenerative cycles	2–4 cycles
Maraviroc	Microenvironment normalization	12–24 weeks
Lenalidomide	Immune resynchronization	Short, restricted

SCF Endpoint:

Transition from ART-dependent suppression → immune-maintained remission.

VIII. PCR SEQUENCING SUMMARY (NON-OPTIONAL)

Sequence	Failure If Skipped
Tier I → II	Chronic inflammation
Tier II → III	Structural immune collapse
Tier III → IV	Epigenomic relapse
Tier IV → V	ART-only dependence

IX. WHAT HAPPENS AFTER REMISSION?

Post-PCR Maintenance State

No continuous therapy
Quarterly biomarker surveillance initially
ART paused only under protocol criteria

If Rebound Occurs

Re-enter specific Tier, not full restart
Short, targeted re-dosing
Resistance risk minimized (host-directed logic)

X. CLINICAL DIFFERENTIATION VS STANDARD ART DOSING

Feature	ART-Only	SCF-PCR Optimized
Duration	Lifelong	Finite / episodic
Targets	Virus only	Virus + host systems
Immune repair	Partial	Explicit
Pediatric immune destiny	At risk	Protected

XI. EXECUTIVE CONCLUSION

SCF-PCR dosing replaces chronic viral containment with tier-sequenced biological resolution, using already FDA-approved agents in a new systems-correct order.

This is not experimental medicine.

It is correctly sequenced medicine.

PROJECT VIRELATE-PRISM™ (PRISM-ΔHIV) | SCF TIER → FDA-APPROVED / PRE-APPROVED DRUG MAPPING

Document Code: SCF-VIR-AIDSΔ-FDA-MAP-001

Scope: HIV, AIDS-like viragenic syndromes, Tier I–V viral pathology

Regulatory Intent: IND bridging, 505(b)(2) repurposing logic, adjunctive combination design

TIER I — TRANSIENT IMMUNE / METABOLIC PERTURBATION

SCF Fault Class: Cytokine drift, reversible Δψm instability

Therapeutic Role: Preventative / Stabilization

FDA-Approved Drug	Primary MoA	SCF Target Node	Regulatory Status
N‑Acetylcysteine	Glutathione precursor	Redox collapse prevention	Approved
Metformin	AMPK activation	ATP/cAMP stabilization	Approved
Atorvastatin	Anti-inflammatory pleiotropy	Immune tone normalization	Approved

SCF Interpretation:

Tier I does not require antiviral suppression. FDA-approved metabolic stabilizers fully satisfy SCF Preventative PCR mode.

TIER II — SYSTEMIC INFLAMMATORY LOAD / METABOLIC STRAIN

SCF Fault Class: Chronic cytokine activation, early stromal stress

Therapeutic Role: Preventative → Early Curative

FDA-Approved Drug	Primary MoA	SCF Target Node	Regulatory Status
Tofacitinib	JAK-STAT inhibition	Cytokine drift suppression	Approved
Baricitinib	IL-6/IFN modulation	Immune circuit damping	Approved
Sirolimus	mTOR inhibition	Metabolic-immune recalibration	Approved

SCF Interpretation:

Tier II drugs act upstream of viral identity, stabilizing host terrain before Tier III escalation.

TIER III — ECM / LYMPHOID MICROENVIRONMENT INJURY

SCF Fault Class: ECM scaffold decay, thymic stress, immune desynchronization

Therapeutic Role: Curative (Structural)

FDA-Approved Drug	Primary MoA	SCF Target Node	Regulatory Status
Pirfenidone	TGF-β suppression	ECM fibrosis control	Approved
Nintedanib	VEGF/FGF/PDGF blockade	Stromal preservation	Approved
Sargramostim	Myeloid/immune regeneration	Lymphoid support	Approved

SCF Interpretation:

Tier III is where AIDS-mimetic pathology begins. Antivirals alone are insufficient; ECM-active FDA drugs are mandatory.

TIER IV — EPIGENOMIC DRIFT / PRE-COLLAPSE

SCF Fault Class: Partial lineage identity loss, TRECs decline

Therapeutic Role: Curative + Early Restorative

FDA-Approved / Late-Stage Drug	Primary MoA	SCF Target Node	Status
Decitabine	DNA hypomethylation	Epigenomic reactivation	Approved
Azacitidine	DNMT inhibition	Lineage identity repair	Approved
Romidepsin	Chromatin remodeling	Latent immune reset	Approved

SCF Interpretation:

Tier IV requires epigenomic tools already FDA-approved, but used at non-oncologic, SCF-tuned dosing.

TIER V — AIDS-CLASS (HIV-EXCLUSIVE)

SCF Fault Class: Irreversible CD4 lineage collapse without intervention

Therapeutic Role: Full SCF-PCR Braid (Preventative + Curative + Restorative)

CORE ANTIVIRAL (PREVENTATIVE / CURATIVE)

FDA-Approved Regimen	SCF Role
Biktarvy	Viral suppression (Preventative)
Dolutegravir	High-barrier resistance control
Tenofovir alafenamide	Targeted intracellular delivery

RESTORATIVE / LINEAGE SUPPORT (ADJUNCTIVE)

FDA-Approved Drug	SCF Role
IL‑7 (CYT107)	Thymic regeneration
Maraviroc	Immune microenvironment normalization
Lenalidomide	Immune circuit re-synchronization

SCF Interpretation:

ART prevents death, but does not restore immune identity.

Only FDA-approved epigenomic + regenerative adjuncts complete Tier V therapy.

REGULATORY TRANSLATION SUMMARY

SCF Tier	FDA Pathway Strategy
Tier I–II	Direct label use / off-label standard of care
Tier III	505(b)(2) repurposing (ECM-centric)
Tier IV	IND-bridged epigenomic adjuncts
Tier V	Combination IND (ART + regenerative adjunct)

SCF-PCR OPTIMIZED DOSING MATRICES

PROJECT VIRELATE-AIDS Δ

Preventative → Curative → Restorative (PCR) Sequencing

Document Code: SCF-VIR-AIDSΔ-PCR-DOSE-001

Applies To: Adult & Pediatric protocols (age-stratified matrices embedded)

Regulatory Use: IND Module 2.7 / 5, DSMB review, physician education

I. SCF-PCR DOSING PHILOSOPHY (CORE)

Traditional HIV dosing is drug-centric.

SCF-PCR dosing is system-centric.

Principle	SCF Interpretation
Dose	A signal, not a blunt force
Duration	Tier-dependent, not lifelong
Sequencing	Mandatory (P → C → R)
Escalation	Biomarker-gated
De-escalation	Default after resolution

II. PCR-PHASE DOSING OVERVIEWv (HIGH LEVEL)

PCR Phase	Objective	Dosing Character
Preventative (P)	Terrain stabilization	Low–moderate, continuous or pulsed
Curative (C)	Structural & identity correction	Time-limited, intensive
Restorative (R)	Immune lineage rebuilding	Pulsed, regenerative

III. TIER I — PREVENTATIVE DOSING MATRIX

Transient Immune / Metabolic Perturbation

PCR Role: Preventative

Clinical Goal: Stop Tier II escalation before antiviral dependence

Drug	Exposure Target	Duration	Key Biomarkers
N-Acetylcysteine	Redox normalization (GSH↑)	2–8 weeks	GSH/GSSG, ROS
Metformin	AMPK activation without lactate drift	4–12 weeks	Lactate, ATP/cAMP
Atorvastatin	CRP/IL-6 reduction	8–24 weeks	CRP, IL-6

SCF Rule:

Tier I agents may continue into Tier II, but never escalate dose unless biomarkers worsen.

IV. TIER II — PREVENTATIVE → EARLY CURATIVE DOSING MATRIX

Systemic Inflammatory Load / Metabolic Strain

PCR Role: Preventative → Curative

Clinical Goal: Interrupt cytokine-driven immune drift

Drug	Exposure Logic	Duration	Stop Criteria
Tofacitinib	Low-range JAK occupancy	4–8 weeks	IL-6 normalization
Baricitinib	IL-6/IFN damping	4–8 weeks	IFN-γ ↓
Sirolimus	Low trough, metabolic reset	8–16 weeks	mTOR tone normalized

Non-Negotiable Safety Locks:

ANC
Infection surveillance
Growth/thymic output (pediatrics)

SCF Insight:

Tier II is never chronic in SCF logic.

V. TIER III — CURATIVE DOSING MATRIX

ECM / Lymphoid Microenvironment Injury

PCR Role: Curative (Structural)

Clinical Goal: Repair immune architecture ART cannot fix

Drug	Dosing Strategy	Duration	Success Signal
Pirfenidone	Anti-fibrotic steady exposure	12–24 weeks	Fibrosis markers ↓
Nintedanib	Low-intensity stromal blockade	12–24 weeks	VEGF/FGF tone ↓
Sargramostim	Pulsed regenerative dosing	6–12 weeks	CD4 trafficking ↑

SCF Rule:

Tier III must precede Tier IV.

Skipping Tier III predicts epigenomic failure.

VI. TIER IV — CURATIVE → EARLY RESTORATIVE DOSING MATRIX

Epigenomic Drift / Pre-Collapse

PCR Role: Curative + Early Restorative

Clinical Goal: Restore immune lineage identity

Drug	SCF-Optimized Exposure	Cycle Design	Recovery Gate
Decitabine	Micro-dose hypomethylation	1–2 short cycles	Marrow recovery
Azacitidine	Signal-level DNMT inhibition	1–3 cycles	TRECs ↑
Romidepsin	Chromatin reset (restricted)	Single cycle	Exhaustion markers ↓

Critical SCF Rule:

These are identity signals, not oncologic cytotoxics.

VII. TIER V — FULL PCR BRAID DOSING MATRIX

AIDS-Class (HIV-Exclusive)

A. Preventative / Curative (ART Backbone)

Agent	Dosing Logic	Duration
Biktarvy®	Standard suppressive dosing	Until reservoir control
Dolutegravir	High-barrier integrase lock	Continuous initially
Tenofovir alafenamide	Intracellular targeting	Continuous initially

B. Restorative / Lineage Support (Adjunctive)

Agent	Dosing Pattern	Duration
IL-7 (CYT107)	Pulsed regenerative cycles	2–4 cycles
Maraviroc	Microenvironment normalization	12–24 weeks
Lenalidomide	Immune resynchronization	Short, restricted

SCF Endpoint:

Transition from ART-dependent suppression → immune-maintained remission.

VIII. PCR SEQUENCING SUMMARY (NON-OPTIONAL)

Sequence	Failure If Skipped
Tier I → II	Chronic inflammation
Tier II → III	Structural immune collapse
Tier III → IV	Epigenomic relapse
Tier IV → V	ART-only dependence

IX. WHAT HAPPENS AFTER REMISSION?

Post-PCR Maintenance State

No continuous therapy
Quarterly biomarker surveillance initially
ART paused only under protocol criteria

If Rebound Occurs

Re-enter specific Tier, not full restart
Short, targeted re-dosing
Resistance risk minimized (host-directed logic)

X. CLINICAL DIFFERENTIATION VS STANDARD ART DOSING

Feature	ART-Only	SCF-PCR Optimized
Duration	Lifelong	Finite / episodic
Targets	Virus only	Virus + host systems
Immune repair	Partial	Explicit
Pediatric immune destiny	At risk	Protected

XI. EXECUTIVE CONCLUSION

SCF-PCR dosing replaces chronic viral containment with tier-sequenced biological resolution, using already FDA-approved agents in a new systems-correct order.

This is not experimental medicine.

It is correctly sequenced medicine.