Tipranavir
| Evidence Level: L4 | Predicted Indications: 10 |
Table of Contents
Tipranavir: From HIV-1 Infection to Congenital Human Immunodeficiency Virus
One-Sentence Summary
Tipranavir is a non-peptidic HIV-1 protease inhibitor originally developed as part of antiretroviral combination therapy for HIV-1 infection. The TxGNN model, together with the evidence pack’s own scoring logic, identifies Congenital Human Immunodeficiency Virus (perinatal/vertical HIV-1 transmission) as the most credible repurposing candidate — a within-class extension of the same antiviral mechanism rather than a novel mechanistic hypothesis. Evidence is currently indirect: 9 clinical trials are available (none Tipranavir-specific, one directly relevant to antiretroviral pharmacokinetics in pregnancy) and 0 dedicated publications, placing this at Evidence Level L4.
Note on candidate selection: TxGNN’s top-ranked predictions by raw score (simian immunodeficiency virus infection, feline AIDS, and several unrelated neoplasms) are explicitly flagged in the evidence pack’s own rationale as animal disease models or embedding noise with “limited clinical relevance.” This report therefore focuses on the highest-ranked candidate that the evidence pack itself elevates to decision stage S1 (“Research Question”) — Congenital HIV Infection — as the only prediction with a coherent mechanistic rationale and supporting trial landscape.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | HIV-1 infection (protease inhibitor class; no formal EU label text available — drug is not marketed) |
| Predicted New Indication | Congenital Human Immunodeficiency Virus |
| TxGNN Prediction Score | 99.83% |
| Evidence Level | L4 |
| EU Market Status | ✗ Not Marketed |
| Number of Authorizations | 0 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism-of-action documentation for tipranavir is not available in the evidence pack (flagged as a High-severity data gap, DG002). Based on the information present in the repurposing rationale, tipranavir is a non-peptidic HIV-1 protease inhibitor, used clinically in combination antiretroviral regimens to block viral maturation by inhibiting the HIV-1 protease enzyme.
Congenital HIV infection refers to vertical (mother-to-child) transmission of HIV-1 — the same virus and the same drug target as the original adult indication. This is therefore not a new mechanistic hypothesis but a population extension of an already-established drug class effect: protease inhibitors are a recognized component of antiretroviral regimens used to prevent and treat perinatal HIV transmission. The related prediction “AIDS related complex” (rank 6, same evidence level) reflects the same logic — it is an older clinical staging term for early symptomatic HIV-1 infection, i.e., the same disease continuum tipranavir already targets.
The key caveat is that none of the identified clinical trials evaluate tipranavir specifically; they study other antiretroviral classes (integrase inhibitors, CCR5 antagonists) or general antiretroviral pharmacokinetics. The mechanistic plausibility is therefore class-based rather than drug-specific, which is consistent with the L4 (mechanism/preclinical-level) evidence grading assigned in the pack.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT02422797 | Phase 3 | Completed | 518 | Non-inferiority switch to dolutegravir + rilpivirine in virologically suppressed HIV-1 adults; not tipranavir-specific (Relevance: Grade C) |
| NCT00197145 | Phase 3 | Terminated | 24 | Placebo-controlled CCR5 antagonist (GW873140) + ritonavir-based optimized background therapy in treatment-experienced HIV; terminated early, low enrollment (Relevance: Grade C) |
| NCT02938520 | Phase 3 | Active, not recruiting | 631 | Open-label switch to long-acting cabotegravir + rilpivirine in ART-naive HIV-1 adults; indirect ART-class evidence (Relevance: Grade C) |
| NCT02429791 | Phase 3 | Completed | 510 | Non-inferiority switch to dolutegravir + rilpivirine, parallel design to NCT02422797; indirect evidence (Relevance: Grade C) |
| NCT03299049 | Phase 3 | Active, not recruiting | 1049 | ATLAS-2M: long-acting cabotegravir + rilpivirine dosing interval (Q8W vs Q4W) in suppressed HIV-1 adults; indirect (Relevance: Grade C) |
| NCT02105987 | Phase 3 | Completed | 555 | STRIIVING: switch to abacavir/dolutegravir/lamivudine fixed-dose combination vs continued regimen in suppressed HIV-1 adults; indirect (Relevance: Grade C) |
| NCT02951052 | Phase 3 | Active, not recruiting | 618 | ATLAS: switch to long-acting IM cabotegravir + rilpivirine vs oral regimen in suppressed HIV-1 adults; indirect (Relevance: Grade C) |
| NCT01641809 | Phase 2 | Completed | 244 | Dose-ranging study of oral GSK1265744 (cabotegravir) + NRTIs for induction, followed by cabotegravir + rilpivirine maintenance in ART-naive HIV-1 adults; indirect (Relevance: Grade C) |
| NCT00042289 | N/A | Completed | 1578 | IMPAACT P1026s: pharmacokinetics of antiretroviral and TB drugs in pregnant and postpartum women and infants, spanning protease inhibitor use; most directly relevant to the perinatal/congenital HIV context, though tipranavir-specific data are not confirmed (Relevance: Grade B) |
Literature Evidence
Currently no related literature available.
EU Market Information
Tipranavir currently has no marketing authorization on file in the EU (market status: Not Marketed, 0 licenses recorded). No EU product, dosage form, or approved indication text is available for this drug.
Safety Considerations
Please refer to the SmPC for safety information. Detailed TFDA/EMA labeling data (warnings, contraindications, drug-drug interactions) were not available at the time of this evaluation and are flagged as a Blocking data gap (DG001) that prevents a complete safety pre-assessment.
Conclusion and Next Steps
Decision: Hold
Rationale:
- All identified clinical trials involve other antiretroviral agents (integrase inhibitors, CCR5 antagonists) rather than tipranavir itself; supporting evidence is class-based/mechanistic (L4), not drug-specific.
- Core safety documentation (warnings, contraindications, DDI profile) is missing and classified as a Blocking data gap, preventing a valid S1 safety assessment.
- The drug has no EU marketing authorization, adding regulatory uncertainty on top of the evidentiary gap.
To proceed, the following is needed:
- TFDA/EMA label data (warnings, contraindications) to close the Blocking data gap (DG001)
- Documented mechanism of action from DrugBank or primary literature to close the High-severity gap (DG002)
- Tipranavir-specific pharmacokinetic and safety data in pregnant women, neonates, and infants (perinatal transmission context), given available evidence is currently limited to other antiretroviral classes
- Dedicated clinical trials or case series evaluating tipranavir in congenital/perinatal HIV populations before advancing beyond the current “Research Question” stage
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.