Abacavir
| 證據等級: L5 | 預測適應症: 10 個 |
目錄
- Abacavir
- AuTxGNN Drug Repurposing Evidence Report: Abacavir
- 1. Executive Summary
- 2. Drug Information
- 3. Predicted New Indications
- Overview Table
- 3.1 Rank 5 — Congenital Human Immunodeficiency Virus
- 3.2 Rank 6 — AIDS-Related Complex (ARC)
- 3.3 Rank 7 — Chronic Hepatitis C Virus Infection
- 3.4 Rank 1 — Simian Immunodeficiency Virus (SIV) Infection
- 3.5 Rank 2 — Feline Acquired Immunodeficiency Syndrome (FIV)
- 3.6 Ranks 3, 4, 8, 9, 10 — No Evidence Predictions
- 4. Evidence Summary
- 5. Safety Considerations
- 6. Recommendations
- 7. Scoring Methodology Reference
- 8. Appendix: Query Log Summary
- Disclaimer
AuTxGNN Drug Repurposing Evidence Report: Abacavir
Candidate ID: TW-DB01048-multi Report Version: v4 Date Generated: 3 April 2026 Data Cutoff: 3 April 2026
1. Executive Summary
This report evaluates Abacavir (DrugBank ID: DB01048), a nucleoside reverse transcriptase inhibitor (NRTI) used in the treatment of HIV-1 infection, across 10 predicted novel indications generated by the TxGNN knowledge graph model. The predictions span a wide range of conditions including lentiviral infections in animals, neurodevelopmental disorders, metabolic conditions, musculoskeletal pathologies, and oncological entities.
Key Findings:
- Two predictions (Rank 5: Congenital HIV; Rank 6: AIDS-related complex) represent on-label or near-on-label extensions of Abacavir’s existing HIV indication and carry strong clinical evidence (Evidence Levels L1 and L2 respectively). These are not true repurposing candidates but confirm the model’s ability to identify pharmacologically coherent drug–disease relationships.
- One prediction (Rank 7: Chronic Hepatitis C) presents a genuinely novel repurposing hypothesis with moderate evidence (L3), including one directly relevant Phase 2 RCT (NCT06356740, PENCIL trial) that is testing Abacavir/Lamivudine for systemic lupus erythematosus — notably mislabelled in the evidence pack but potentially relevant via shared interferon pathway modulation. Extensive literature on Abacavir’s interactions with HCV therapy in co-infected patients exists.
- Two predictions (Rank 1: SIV infection; Rank 2: Feline AIDS) involve veterinary/non-human diseases with limited in vitro evidence. These are not applicable to human therapeutics.
- Five predictions (Ranks 3, 4, 8, 9, 10) lack any supporting evidence and have no plausible mechanistic rationale.
TGA Registration Status: Abacavir is registered on the Australian Register of Therapeutic Goods (ARTG) as the brand name Ziagen (as monotherapy) and in fixed-dose combinations including Kivexa (abacavir/lamivudine) and Triumeq (abacavir/dolutegravir/lamivudine).
Critical Data Gaps: TGA-approved Product Information (PI) warnings/contraindications and detailed mechanism of action data were not available in this evidence pack and represent blocking gaps for safety assessment.
2. Drug Information
| Parameter | Detail |
|---|---|
| INN (Generic Name) | Abacavir (as abacavir sulfate) |
| DrugBank ID | DB01048 |
| ATC Code | J05AF06 |
| Drug Class | Nucleoside Reverse Transcriptase Inhibitor (NRTI) |
| Australian Brand Names | Ziagen®, Kivexa® (with lamivudine), Triumeq® (with dolutegravir/lamivudine) |
| ARTG Status | Registered (multiple formulations) |
| Mechanism of Action | [Data Gap — not provided in evidence pack] Abacavir is a guanosine analogue that is phosphorylated intracellularly to its active metabolite carbovir triphosphate (CBV-TP), which competitively inhibits HIV-1 reverse transcriptase and acts as a chain terminator of viral DNA synthesis. |
Current TGA-Approved Indications
Abacavir is indicated in antiretroviral combination therapy for the treatment of Human Immunodeficiency Virus (HIV-1) infection in adults and children aged ≥3 months.
Available Formulations (Australia)
- Ziagen: 300 mg tablets; 20 mg/mL oral solution
- Kivexa: 600 mg abacavir / 300 mg lamivudine tablets
- Triumeq: 600 mg abacavir / 50 mg dolutegravir / 300 mg lamivudine tablets
- Paediatric dispersible tablet formulations
3. Predicted New Indications
Overview Table
| Rank | Disease | TxGNN Score | Evidence Level | Decision Stage | Recommendation |
|---|---|---|---|---|---|
| 1 | Simian immunodeficiency virus infection | 0.998 | L4 | S0 | Hold |
| 2 | Feline acquired immunodeficiency syndrome | 0.998 | L3 | S0 | Hold |
| 3 | Neurodevelopmental disorder with ataxic gait | 0.998 | L5 | S0 | Hold |
| 4 | Obsolete familial combined hyperlipidaemia | 0.987 | L5 | S0 | Hold |
| 5 | Congenital human immunodeficiency virus | 0.928 | L1 | S3 | Proceed with Guardrails |
| 6 | AIDS-related complex | 0.928 | L2 | S3 | Proceed with Guardrails |
| 7 | Chronic hepatitis C virus infection | 0.927 | L3 | S1 | Research Question |
| 8 | Paratenonitis | 0.882 | L5 | S0 | Hold |
| 9 | Calcific tendinitis | 0.879 | L5 | S0 | Hold |
| 10 | Fibroma of prostate | 0.870 | L5 | S0 | Hold |
3.1 Rank 5 — Congenital Human Immunodeficiency Virus
| **Evidence Level: L1 | Decision Stage: S3 | Recommendation: Proceed with Guardrails** |
Disease Description
Congenital (perinatally acquired) HIV refers to HIV-1 infection transmitted from mother to child during pregnancy, labour, delivery, or breastfeeding. Without intervention, vertical transmission rates range from 15–45%. Early initiation of antiretroviral therapy (ART) is critical for infant survival and long-term outcomes.
Biological Rationale
Direct mechanistic link. Abacavir is an already approved HIV NRTI; congenital HIV is fundamentally the same viral infection acquired via vertical transmission. Abacavir has TGA/FDA-approved paediatric formulations (oral solution for infants ≥3 months; dispersible tablets). This prediction represents an on-label extension rather than a genuine repurposing candidate, confirming that Abacavir’s existing indication encompasses this disease entity.
Clinical Trial Evidence
A substantial body of 24 clinical trials was identified on ClinicalTrials.gov. Key trials with graded relevance:
| NCT ID | Phase | N | Status | Relevance | Key Finding |
|---|---|---|---|---|---|
| NCT00102960 | Phase 3 | 377 | Completed | A | ART strategies in perinatally infected infants |
| NCT02422797 | Phase 3 | 518 | Completed | A | DTG+RPV switch from ABC-containing regimens |
| NCT02429791 | Phase 3 | 510 | Completed | A | DTG+RPV non-inferiority vs ABC-containing ART |
| NCT03299049 | Phase 3 | 1,049 | Active | A | CAB LA+RPV LA (ATLAS-2M), ABC backbone |
| NCT02938520 | Phase 3 | 631 | Active | A | FLAIR study, ABC/DTG/3TC induction |
| NCT02105987 | Phase 3b | 555 | Completed | A | STRIIVING: switch to ABC/DTG/3TC |
| NCT03016533 | Phase 3 | 100 | Completed | A | IMPAACT paediatric DTG access |
| NCT01910402 | Phase 3b | 499 | Completed | A | DTG/ABC/3TC in ART-naïve women |
Literature Evidence
7 publications identified, including:
- PENTA 5 Trial (Lancet, 2002; PMID 11888583) — Tier 1 RCT comparing dual NRTI regimens ± nelfinavir in treatment-naïve children with HIV-1.
- IMPAACT 2010/VESTED (JAIDS, 2024; PMID 39742354) — Tier 2 cohort study on pregnancy outcomes in women on ART including abacavir-containing regimens.
- ANRS CO1/CO11 French Perinatal Cohort (PLoS Medicine, 2014; PMID 24781315) — Tier 2 cohort analysis of birth defects associated with prenatal ART exposure.
Assessment
This is a validated on-label indication. Abacavir is a cornerstone of paediatric HIV treatment globally, including in Australian clinical practice guidelines (ASHM HIV Management Guidelines). The extensive Phase 3 trial evidence (>4,000 combined participants) supports its established role. No repurposing action is required.
3.2 Rank 6 — AIDS-Related Complex (ARC)
| **Evidence Level: L2 | Decision Stage: S3 | Recommendation: Proceed with Guardrails** |
Disease Description
AIDS-related complex (ARC) is a historical term describing the symptomatic stage of HIV infection characterised by constitutional symptoms (fever, weight loss, lymphadenopathy, diarrhoea) and immunological decline, preceding the formal diagnosis of AIDS. While the term has largely been superseded by modern HIV staging systems (CDC classification), it remains in clinical ontologies.
Biological Rationale
Direct mechanistic link. ARC is a clinical stage of HIV-1 infection. Abacavir’s NRTI mechanism directly suppresses HIV replication at this disease stage. The compound 1592U89 referenced in early trials (NCT00002364) is Abacavir’s developmental code name. This is essentially an on-label application.
Clinical Trial Evidence
| NCT ID | Phase | N | Status | Relevance | Key Finding |
|---|---|---|---|---|---|
| NCT00002364 | Phase 2 | 40 | Completed | A | Early exploratory study of 1592U89 (Abacavir) in NRTI-experienced patients |
| NCT00001119 | N/A | 288 | Completed | B | Combination ART in acute HIV-1, Abacavir as component |
Literature Evidence
14 PubMed articles identified. Notable publications:
- Brew et al. (PLoS Clinical Trials, 2007; PMID 17401456) — Tier 1 clinical trial analysis evaluating Abacavir added to background ART for AIDS dementia complex (ADC), directly relevant to ARC-stage neurological complications.
- Silverberg et al. (AIDS, 2024; PMID 37967231) — Tier 2 cohort study on initial ART regimen and heart failure risk, relevant to long-term safety.
- Multiple Tier 2 reviews on drug hypersensitivity (PMID 17620824, 21480946) relevant to Abacavir’s known HLA-B*57:01-associated hypersensitivity reaction.
Assessment
This is another validated on-label indication. Abacavir is used at all stages of HIV infection including the symptomatic pre-AIDS phase. No repurposing action is required.
3.3 Rank 7 — Chronic Hepatitis C Virus Infection
| **Evidence Level: L3 | Decision Stage: S1 | Recommendation: Research Question** |
Disease Description
Chronic hepatitis C virus (HCV) infection is a blood-borne viral disease affecting approximately 130,000 Australians. Untreated chronic HCV leads to progressive liver fibrosis, cirrhosis, hepatocellular carcinoma, and liver failure. Australia has committed to HCV elimination by 2030, with direct-acting antivirals (DAAs) available on the PBS since 2016.
Biological Rationale
Indirect mechanistic link. Abacavir targets HIV reverse transcriptase and has no known direct activity against HCV RNA-dependent RNA polymerase (NS5B). However, several hypotheses warrant consideration:
- Reverse transcriptase inhibition of endogenous retroelements: NRTIs may inhibit LINE-1 retrotransposon activity, which has been implicated in innate immune activation and interferon signalling in autoimmune and chronic inflammatory conditions.
- Immunomodulatory effects: Abacavir may modulate type I interferon pathways indirectly.
- P-glycoprotein interactions: In vitro evidence (PMID 31481446) demonstrates that Abacavir inhibits P-glycoprotein efflux, potentially affecting intracellular concentrations of co-administered HCV DAAs.
- HIV/HCV co-infection management: The majority of literature addresses Abacavir as background ART in HIV/HCV co-infected patients receiving HCV treatment, not as a direct anti-HCV agent.
Important caveat: Multiple studies (PMID 18572756, 20167995) have reported reduced HCV treatment response in patients receiving Abacavir-containing ART with pegylated interferon/ribavirin, possibly due to intracellular competition between abacavir and ribavirin (both guanosine analogues). This represents a potential negative signal.
Clinical Trial Evidence
| NCT ID | Phase | N | Status | Relevance | Key Finding |
|---|---|---|---|---|---|
| NCT06356740 (PENCIL) | Phase 2 | 70 | Not yet recruiting | A | RCT of ABC/3TC for SLE (note: mislabelled as HCV in evidence pack; tests reverse transcriptase inhibitor hypothesis in autoimmunity) |
| NCT01908660 (HEPAVIR) | N/A | 192 | Completed | B | Hepatic safety of ART including Abacavir in HIV/HCV co-infected patients |
| NCT01500616 | Phase 3 | 122 | Completed | C | Telaprevir for HCV in HIV co-infection; Abacavir as background ART only |
Literature Evidence
20 PubMed articles identified. Key publications:
- Vispo et al. (Antiviral Therapy, 2008; PMID 18572756) — Low response to PEG-IFN/RBV in HIV/HCV patients on Abacavir. Negative signal.
- Fuchs et al. (JAC, 2016; PMID 26869690) — Plasma and intracellular ribavirin concentrations not significantly altered by Abacavir.
- Mira et al. (JAC, 2008; PMID 18854330) — Comparison of HCV therapy efficacy with Abacavir vs tenofovir NRTI backbones in co-infected patients.
- Martinec et al. (AAC, 2019; PMID 31481446) — Abacavir inhibits P-glycoprotein efflux in Caco-2 cells and intestinal slices.
- Brunet et al. (CID, 2016; PMID 26400998) — Liver fibrosis progression with ABC/3TC vs TDF/FTC backbones in HIV/HCV co-infection.
Assessment
The evidence for Abacavir as a direct anti-HCV agent is weak and largely circumstantial. Most clinical data pertains to Abacavir as background ART in co-infected patients, with some studies suggesting a negative interaction with ribavirin-based HCV therapy. The PENCIL trial (NCT06356740) tests ABC/3TC in systemic lupus erythematosus (not HCV), though the underlying hypothesis of retrotransposon inhibition could theoretically extend to HCV-associated immune dysregulation. In the current Australian context, highly effective DAAs (sofosbuvir/velpatasvir, glecaprevir/pibrentasvir) are PBS-listed with cure rates >95%, making Abacavir repurposing for HCV clinically unnecessary. This remains a research question only.
3.4 Rank 1 — Simian Immunodeficiency Virus (SIV) Infection
| **Evidence Level: L4 | Decision Stage: S0 | Recommendation: Hold** |
Assessment
SIV is a non-human primate lentivirus. While phylogenetically related to HIV, SIV infection is not a human disease and therefore not a valid repurposing target for clinical application. One in vitro susceptibility study (PMID 15040537, Witvrouw et al., Antiviral Therapy, 2004) evaluated anti-HIV-1 compounds against SIV strains, demonstrating the research utility of cross-species antiviral testing but not a therapeutic opportunity. Not applicable to human medicine.
3.5 Rank 2 — Feline Acquired Immunodeficiency Syndrome (FIV)
| **Evidence Level: L3 | Decision Stage: S0 | Recommendation: Hold** |
Assessment
Feline immunodeficiency virus (FIV) is a veterinary pathogen. One in vitro study (PMID 11684314, Bisset et al., Antiviral Research, 2002) demonstrated that ZDV/3TC/ABC combination suppressed FIV replication in cell culture. All four clinical trials retrieved (NCT01263015, NCT01227824, NCT00951015, NCT01499199) are human HIV trials unrelated to FIV (search false positives). While the FIV-cat model has value in HIV research, this is not a human repurposing opportunity.
3.6 Ranks 3, 4, 8, 9, 10 — No Evidence Predictions
| Rank | Disease | Rationale for Hold |
|---|---|---|
| 3 | Neurodevelopmental disorder with ataxic gait, absent speech, and decreased cortical white matter | Rare genetic disorder; no NRTI mechanism relevant to neurodevelopment. High TxGNN score likely reflects topological proximity to HIV encephalopathy in the knowledge graph. |
| 4 | Obsolete familial combined hyperlipidaemia | Ontology term marked as “obsolete.” NRTIs including Abacavir are associated with worsening dyslipidaemia as an adverse effect — a contraindication signal. |
| 8 | Paratenonitis | Mechanical/inflammatory tendon sheath condition; no NRTI anti-inflammatory mechanism. |
| 9 | Calcific tendinitis | Calcium deposition disorder; Abacavir has no calcium metabolism or tendon repair activity. |
| 10 | Fibroma of prostate | Benign mesenchymal tumour; no anti-tumour or anti-fibrotic NRTI mechanism. |
4. Evidence Summary
4.1 Evidence Sources Queried
| Source | Queries Executed | Successful | Results Found |
|---|---|---|---|
| TGA/TFDA | 1 | 1 | 0 licences |
| DrugBank | 1 | 1 | 1 record |
| ClinicalTrials.gov | 10 | 10 | 33 trials total |
| ICTRP | 10 | 10 | 0 trials |
| PubMed | 10 | 10 | 43 articles total |
| ANZCTR | Not queried | — | — |
4.2 Evidence Distribution by Indication
| Indication | Clinical Trials | PubMed Articles | Total Evidence Items |
|---|---|---|---|
| Congenital HIV | 24 | 7 | 31 |
| AIDS-related complex | 2 | 14 | 16 |
| Chronic HCV | 3 | 20 | 23 |
| Feline AIDS | 4 (all false positives) | 1 | 5 |
| SIV infection | 0 | 1 | 1 |
| All other (5 indications) | 0 | 0 | 0 |
4.3 ANZCTR Gap
No Australian New Zealand Clinical Trials Registry (ANZCTR) search was conducted. Future iterations should include ANZCTR queries to capture Australia-specific trial data relevant to HIV management and any novel Abacavir indications.
5. Safety Considerations
5.1 Known Adverse Effects
⚠️ Data Gap (DG001 — Blocking): Full TGA Product Information warnings and contraindications were not available in this evidence pack. The following is based on established pharmacological knowledge.
Black Box Warning (International):
- HLA-B57:01 Hypersensitivity Reaction:** Potentially fatal hypersensitivity syndrome characterised by fever, rash, gastrointestinal symptoms, respiratory symptoms, and constitutional symptoms. **HLA-B57:01 screening is mandatory before prescribing in Australia (PBS requirement). Prevalence of HLA-B*57:01 is approximately 6–8% in Caucasian Australians.
Common Adverse Effects:
- Nausea, vomiting, diarrhoea
- Headache, fatigue
- Hyperlipidaemia (particularly relevant to Rank 4 prediction)
Serious Adverse Effects:
- Lactic acidosis / severe hepatomegaly with steatosis (class effect of NRTIs)
- Immune reconstitution inflammatory syndrome (IRIS)
- Cardiovascular risk: Some epidemiological studies have associated Abacavir use with increased myocardial infarction risk (D:A:D study), though this remains debated
5.2 Contraindications
- [Data Gap — DG001]
- Known HLA-B*57:01 positive status (mandatory screening in Australia)
- Prior hypersensitivity reaction to Abacavir (must never be re-challenged)
- Moderate to severe hepatic impairment (for Abacavir-containing FDCs)
5.3 Drug–Drug Interactions
| Parameter | Status |
|---|---|
| DDI query status | Not found in evidence pack |
| Total interactions identified | 0 |
Known significant interactions from pharmacological literature:
- Ribavirin: Potential intracellular competition (both guanosine analogues); may reduce HCV treatment efficacy — directly relevant to Rank 7 prediction
- Methadone: Increased methadone clearance; dose adjustment may be required
- Alcohol: Increased Abacavir AUC (~41%) due to shared alcohol dehydrogenase metabolism
- Tipranavir/ritonavir: May decrease Abacavir concentrations
5.4 Australian Prescribing Considerations
- HLA-B*57:01 testing is required before initiation (Medicare-rebatable pathology test)
- Abacavir is PBS-listed under Section 85 for HIV treatment (Authority Required)
- Prescribing is generally initiated by infectious diseases physicians or sexual health specialists
- ASHM (Australasian Society for HIV, Viral Hepatitis, and Sexual Health Medicine) guidelines recommend HLA testing, cardiovascular risk assessment, and viral resistance testing prior to commencement
6. Recommendations
6.1 Evidence Strength Assessment
| Category | Assessment |
|---|---|
| Strongest predictions | Rank 5 (Congenital HIV) and Rank 6 (ARC) — both are essentially on-label; no repurposing action needed |
| Only genuine repurposing candidate | Rank 7 (Chronic HCV) — weak/indirect evidence; research question only |
| Veterinary/non-human | Ranks 1 and 2 — not applicable to human therapeutics |
| No evidence / no rationale | Ranks 3, 4, 8, 9, 10 — hold; no further action |
6.2 Suggested Next Steps
For Chronic HCV (Rank 7) — If Further Investigation Is Desired:
- Monitor PENCIL Trial (NCT06356740): Although this trial tests ABC/3TC in SLE (not HCV), results may inform the retrotransposon inhibition hypothesis applicable to other interferon-driven conditions.
- Systematic Review: Conduct a formal systematic review of Abacavir’s effect on HCV treatment outcomes in co-infected patients, reconciling conflicting data (negative signal from Vispo et al. vs neutral signal from Fuchs et al.).
- In Vitro Testing: If the retrotransposon hypothesis is to be pursued, in vitro assays evaluating Abacavir’s effect on LINE-1 activity in HCV-infected hepatocytes would be informative.
- Australian Context Consideration: Given that highly effective DAAs (>95% cure rates) are PBS-listed and widely accessible in Australia, the clinical utility of Abacavir for HCV is negligible. Investigation would be of mechanistic/academic interest only.
Critical Data Gaps to Resolve:
| Gap ID | Item | Severity | Remediation |
|---|---|---|---|
| DG001 | TGA PI warnings/contraindications | Blocking | Download and parse current Ziagen/Kivexa/Triumeq PI from TGA website |
| DG002 | Mechanism of action detail | High | Query DrugBank API for full MOA, targets, pathways |
| — | ANZCTR trials | Medium | Query ANZCTR for Australian-specific Abacavir trials |
| — | DDI data | Medium | Query TGA or DrugBank for comprehensive interaction profile |
6.3 Relevant Australian Research Institutions
- Kirby Institute, UNSW Sydney — HIV epidemiology and clinical trials
- Peter Doherty Institute for Infection and Immunity, Melbourne — HIV and viral hepatitis research
- Burnet Institute, Melbourne — Disease elimination programmes
- ASHM (Australasian Society for HIV, Viral Hepatitis, and Sexual Health Medicine) — Clinical guidelines and education
- National Centre for HIV Epidemiology and Clinical Research — Surveillance and cohort studies
7. Scoring Methodology Reference
| Level | Definition |
|---|---|
| L1 | ≥1 Phase 3 RCT with direct relevance |
| L2 | Phase 2 trials or strong observational evidence |
| L3 | In vitro/animal studies or indirect clinical evidence |
| L4 | Single preclinical study or case reports only |
| L5 | No evidence identified |
| Stage | Definition |
|---|---|
| S0 | Prediction only; insufficient evidence to evaluate |
| S1 | Research question identified; warrants literature review |
| S2 | Preclinical validation warranted |
| S3 | Clinical evidence exists; proceed with guardrails |
8. Appendix: Query Log Summary
A total of 33 evidence queries were executed across 5 data sources on 9 March 2026. All queries returned successfully. The highest evidence yield was for congenital HIV (24 clinical trials, 7 PubMed articles) and chronic HCV (3 clinical trials, 20 PubMed articles). Five of ten predicted indications returned zero evidence across all sources.
Research Use Only: This report is generated for research purposes only and does not constitute medical advice. Drug repurposing predictions require clinical validation before therapeutic application. This is not a TGA-approved assessment. All predicted indications require independent verification by qualified healthcare professionals before any clinical consideration. HLA-B*57:01 screening is mandatory before any use of Abacavir in Australia.
Generated by AuTxGNN — Australia Drug Repurposing Predictions Report ID: TW-DB01048-multi-v4 | 3 April 2026
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.