Rilpivirine

證據等級: L5

預測適應症: 5 個

Rilpivirine: From HIV-1 Infection to Congenital HIV (Mother-to-Child Transmission Prevention)

One-Sentence Summary

Rilpivirine (DB08864) is a non-nucleoside reverse transcriptase inhibitor (NNRTI) already used as part of oral and long-acting injectable (CAB LA/RPV LA) antiretroviral regimens for HIV-1 infection. This evidence pack's strongest TxGNN-predicted signal points to congenital HIV (perinatal/mother-to-child transmission), supported by 28 clinical trials (including multiple completed Phase 3 RCTs) and 5 publications focused on pregnancy pharmacokinetics and safety. Four other candidate indications were also flagged by TxGNN in this pack but carry markedly weaker or non-human evidence (see note below).

Quick Overview

Item	Content
Original Indication	HIV-1 infection (NNRTI-based antiretroviral therapy) — drawn from trial descriptions in this evidence pack; no formal MOA/indication record on file
Predicted New Indication	Congenital human immunodeficiency virus (perinatal/vertical transmission prevention)
TxGNN Prediction Score	99.56%
Evidence Level	L1
Market Status	Not marketed (0 authorizations on file)
Number of Authorizations	0
Recommended Decision	Proceed with Guardrails

Why is This Prediction Reasonable?

Currently, no formal mechanism-of-action record exists in the drug-level fields for Rilpivirine (flagged as a data gap in this pack). However, the clinical trial and literature evidence gathered here consistently describes rilpivirine as an NNRTI that blocks HIV-1 reverse transcriptase, and it is a component of both oral regimens and the long-acting injectable cabotegravir/rilpivirine (CAB LA/RPV LA) regimen approved for HIV-1 infection.

The core strategy for preventing vertical/perinatal HIV transmission is suppression of maternal viral load. Since rilpivirine directly blocks reverse transcriptase and interrupts viral replication, its mechanism maps directly onto congenital-HIV prevention — this is less a novel repurposing hypothesis and more a logical extension of its existing antiviral action into the pregnant/perinatal population. The main open questions are pharmacokinetic: literature in this pack shows rilpivirine plasma concentrations drop 70–75% during pregnancy with the long-acting injectable formulation, and fetal/infant safety data are still accumulating, which is why guardrails rather than an unqualified "Go" are warranted.

Note on other TxGNN-flagged candidates in this pack: TxGNN also scored feline acquired immunodeficiency syndrome, simian immunodeficiency virus infection, and a rare neurodevelopmental disorder as high-probability matches. These were assessed as low-confidence: feline AIDS and SIV are non-human veterinary/primate-model indications outside the human repurposing scope (Hold / Research Question), and the neurodevelopmental disorder has no clinical trial or literature support at all and is flagged in the source rationale as a likely false-positive candidate (Hold). "AIDS related complex" (rank 4) scored similarly to congenital HIV but is essentially the same underlying HIV-1 indication under an older staging term, so it is not treated as a distinct repurposing opportunity here.

Clinical Trial Evidence

Trial Number	Phase	Status	Enrollment	Key Findings
NCT02951052	Phase 3	Active, not recruiting	618	ATLAS study — switching virologically suppressed HIV-1 adults to long-acting IM cabotegravir + rilpivirine
NCT05896748	Phase 3	Completed	94	FLAIR sub-study comparing subcutaneous vs. intramuscular administration of CAB/RPV long-acting injections
NCT01266902	Phase 3	Completed	482	TMC278 (rilpivirine) 25 mg qd continued-access study — pivotal registration-supporting trial
NCT00855335	Phase 3	Completed	77	Pharmacokinetics of darunavir, etravirine, and rilpivirine specifically in HIV-1 infected pregnant women
NCT00042289	N/A (Phase 4)	Completed	1578	IMPAACT P1026s — pharmacokinetics of antiretrovirals and TB drugs during pregnancy and postpartum
NCT03497676	Phase 1/2	Completed	168	Safety, tolerability and PK of oral/long-acting CAB and long-acting rilpivirine in HIV-infected children and adolescents
NCT02494986	Phase 2	Active, not recruiting	48	Continued-access rollover study of rilpivirine in participants from pediatric rilpivirine studies
NCT07412977	N/A	Not yet recruiting	5160	VIROPREG — French prospective cohort assessing viral infections (incl. HIV) and antiviral treatment impact during pregnancy on maternal/child health
NCT02938520	Phase 3	Active, not recruiting	631	FLAIR — long-acting IM cabotegravir + rilpivirine maintenance after switch from an integrase-inhibitor regimen
NCT03299049	Phase 3	Active, not recruiting	1049	ATLAS-2M — long-acting CAB + RPV dosed every 8 vs. every 4 weeks

18 additional trials in this pack were not included above; full list available in the source evidence file.

Literature Evidence

PMID	Year	Type	Journal	Key Findings
41225339	2025	Systematic Review/Meta-analysis	BMC Infectious Diseases	Safety of cabotegravir (co-administered with rilpivirine) in pregnancy
36411596	2023	Cohort/PK study	HIV Medicine	Pregnancy outcomes and PK in women exposed to long-acting cabotegravir + rilpivirine in clinical trials
38864586	2024	Cohort	AIDS (London, England)	First-trimester exposure to newer antiretrovirals (incl. rilpivirine) and congenital anomalies in a US cohort
38703388	2024	Case Report	Clinical Infectious Diseases	Long-acting CAB/RPV in a pregnant woman with HIV — RPV levels 70–75% lower during pregnancy, no vertical transmission or malformation
41268510	2025	Case Report	Case Reports in Infectious Diseases	Long-acting CAB/RPV maintained viral suppression throughout pregnancy; literature review

Safety Considerations

Please refer to the package insert for safety information.

Conclusion and Next Steps

Decision: Proceed with Guardrails

Rationale: Multiple completed Phase 3 RCTs establish rilpivirine's efficacy and safety as part of oral and long-acting antiretroviral regimens (L1 evidence), and an emerging body of pregnancy-specific PK, cohort, and case-report data supports its mechanistic applicability to congenital HIV prevention. However, long-acting rilpivirine shows markedly reduced plasma exposure during pregnancy and remains an off-label use in this population, so guardrails around monitoring and dosing are warranted rather than an unqualified proceed.

To proceed, the following is needed:

TFDA/local package insert warnings and contraindications (currently a blocking data gap, DG001)
Formal mechanism-of-action documentation at the drug level (DG002)
Drug-drug interaction profile (current DDI query returned no results)
Completion and grading of the 18 remaining, currently ungraded clinical trials in this evidence set
A dedicated maternal/fetal safety and dosing evaluation before recommending long-acting RPV in pregnant populations
Disclaimer

This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.