Abacavir

證據等級: L5

預測適應症: 10 個

Abacavir: From HIV Infection to Congenital Human Immunodeficiency Virus

One-Sentence Summary

Abacavir is a nucleoside reverse transcriptase inhibitor (NRTI) used in combination antiretroviral therapy for HIV-1 infection. The TxGNN model generated 10 predicted indications; after filtering out animal-model targets (SIV, FIV at ranks 1–2) and obsolete/non-translatable disease terms (ranks 3–4), the most clinically actionable prediction is Congenital Human Immunodeficiency Virus (rank 5), supported by 8+ Phase 2/3 clinical trials and 7 publications, with an evidence level of L1.

Quick Overview

Item	Content
Original Indication	HIV-1 infection (adult combination antiretroviral therapy)
Predicted New Indication	Congenital Human Immunodeficiency Virus
TxGNN Prediction Score	92.76%
Evidence Level	L1
Singapore Market Status	✗ Not marketed
Number of Registrations	0
Recommended Decision	Proceed with Guardrails

Why is This Prediction Reasonable?

Abacavir is a synthetic deoxyguanosine analogue. After cellular uptake, it undergoes sequential phosphorylation to its active form, carbovir triphosphate (carbovir-TP). Carbovir-TP competes with the natural substrate deoxyguanosine-5'-triphosphate for the HIV-1 reverse transcriptase active site, causing obligate DNA chain termination. This mechanism is shared by all strains of HIV-1 regardless of patient age or route of acquisition.

Congenital (perinatal) HIV arises from vertical mother-to-child transmission of HIV-1 during pregnancy, delivery, or breastfeeding. The target pathogen is identical to that in adult HIV, and the pharmacological target — HIV-1 reverse transcriptase — is structurally unchanged in neonatal and infant infection. Abacavir's established antiviral efficacy therefore translates directly to this population. Paediatric dispersible formulations of the ABC/3TC fixed-dose combination and the three-in-one ABC/DTG/3TC tablet have been specifically developed and validated to support weight-based dosing in children.

Multiple large Phase 3 randomised controlled trials have demonstrated the efficacy and safety of ABC/3TC-containing regimens in HIV-infected infants, children, adolescents, and their mothers. The ABC/3TC backbone is currently listed as a preferred NRTI scaffold in both WHO and DHHS paediatric HIV treatment guidelines, and the landmark PENTA 5 and IMPAACT programme trials have built a robust evidence base for this indication. The primary safety guardrail is mandatory pre-treatment HLA-B*57:01 genotyping to eliminate the risk of potentially fatal hypersensitivity reactions.

Clinical Trial Evidence

Trial Number	Phase	Status	Enrollment	Key Findings
NCT00102960	Phase 3	Completed	377	Compares ART strategies of different durations in HIV-infected infants shortly after primary infection in resource-limited settings; Abacavir included as a backbone option — foundational evidence for paediatric/congenital HIV treatment
NCT02105987	Phase 3	Completed	555	STRIIVING: non-inferiority trial switching virologically suppressed HIV-1 adults to ABC/DTG/3TC FDC versus continuing current regimen; establishes durability of ABC/3TC backbone over 48 weeks
NCT02422797	Phase 3	Completed	518	SWORD-1: DTG + rilpivirine versus current ART (including ABC/3TC backbone) in virologically suppressed HIV-1 adults; two-drug regimen non-inferior over 96 weeks
NCT02429791	Phase 3	Completed	510	SWORD-2: independent confirmatory parallel trial of SWORD-1; both trials together provide strong Level 1 evidence for ABC/3TC as a switching anchor
NCT01910402	Phase 3	Completed	499	DTG/ABC/3TC FDC versus ATV+RTV+TDF/FTC in ART-naïve HIV-1-infected women; non-inferior at 48 weeks, important for PMTCT-adjacent populations
NCT02938520	Phase 3	Active, not recruiting	631	FLAIR: long-acting cabotegravir + rilpivirine after induction on ABC/DTG/3TC; validates ABC/3TC as induction backbone for next-generation maintenance strategies
NCT03299049	Phase 3	Active, not recruiting	1,049	ATLAS-2M: Q8W vs Q4W long-acting CAB+RPV; ABC/3TC used as current standard-of-care comparator — largest ongoing trial in this evidence set
NCT02951052	Phase 3	Active, not recruiting	618	ATLAS: long-acting CAB+RPV switch from current ART; provides ongoing real-world durability data for ABC/3TC-containing regimens
NCT03016533	Phase 3	Completed	100	Open-label dolutegravir access for HIV-infected children and adolescents completing IMPAACT P1093/P2019; Abacavir used as background NRTI — paediatric safety data
NCT02893488	Phase 1	Completed	20	Relative bioavailability of dispersible DTG/ABC/3TC paediatric tablet under four dosing conditions; directly supports neonatal/infant pharmacokinetics for congenital HIV

Literature Evidence

PMID	Year	Type	Journal	Key Findings
11888583	2002	RCT	Lancet	PENTA 5: dual-NRTI regimens ± nelfinavir in previously untreated HIV-1 children — foundational paediatric HIV RCT demonstrating NRTI backbone efficacy in children
39742354	2024	RCT Follow-up	J Acquir Immune Defic Syndr	Subsequent pregnancies in IMPAACT 2010/VESTED: women with HIV face elevated adverse pregnancy outcomes; timing of ART — including ABC-based regimens — influences maternal–fetal risk
29406430	2018	Cohort	J Acquir Immune Defic Syndr	Italian national cohort: ABC/3TC versus TDF/FTC in pregnant HIV women; comparable laboratory and clinical outcomes, supporting ABC/3TC use in pregnancy (PMTCT context)
24781315	2014	Registry Cohort	PLoS Medicine	French perinatal cohort (ANRS CO1/CO11): association between prenatal ART exposure and birth defects; critical teratogenicity safety dataset for congenital HIV prevention programmes
31441211	2019	Cross-sectional	J Int AIDS Soc	South African adolescents with perinatally acquired HIV on ART: multisystem impairment across neurocognitive, cardiovascular, respiratory, and renal domains — informs long-term monitoring needs
34151853	2021	Case Report	J Neuromuscul Dis	Five-year-old with congenital HIV on ABC-containing regimen develops inflammatory myositis; raises awareness of ART-associated musculoskeletal adverse events in paediatric patients
28458904	2017	Case Report	Endocrinol Diabetes Metab Case Rep	Paediatric congenital HIV patient on ABC/3TC + lopinavir/ritonavir develops iatrogenic Cushing syndrome upon addition of intranasal fluticasone furoate; critical DDI safety signal via CYP3A4 inhibition by ritonavir boosting

Singapore Market Information

Abacavir currently has no registered products in Singapore (HSA total registrations: 0).

If procurement is considered for a compassionate use or clinical trial setting, reference products available globally include:

Brand Name	Formulation	Indication
Ziagen® (GlaxoSmithKline)	300 mg tablet; 20 mg/mL oral solution	HIV-1 infection (adult and paediatric)
Epzicom® / Kivexa® (GSK)	ABC 600 mg / 3TC 300 mg FDC tablet	HIV-1 infection
Triumeq® (ViiV Healthcare)	ABC 600 mg / DTG 50 mg / 3TC 300 mg FDC tablet	HIV-1 infection
Triumeq PD® (ViiV Healthcare)	Dispersible FDC tablet (paediatric weight-band dosing)	HIV-1 infection in children

Safety Considerations

Singapore-specific package insert data (formal warnings and contraindications) are not available in this evidence pack. Based on clinical evidence cited within:

HLA-B*57:01 Hypersensitivity Reaction: Abacavir causes a well-characterised, potentially fatal immune-mediated hypersensitivity syndrome in HLA-B*57:01 carriers (estimated prevalence ~5–8% in White European populations; lower in Asian populations). Pre-treatment HLA-B*57:01 genotyping is mandatory before initiation and is non-negotiable in any treatment programme, including paediatric congenital HIV. Rechallenge after a confirmed reaction is absolutely contraindicated (PMID 26372480; PMID 17620824; PMID 21480946).
Drug Interaction — Inhaled/Intranasal Corticosteroids + Ritonavir-boosted Regimens: When Abacavir is co-administered with lopinavir/ritonavir (or other ritonavir-boosted PIs), co-prescription of even low-dose inhaled or intranasal corticosteroids (e.g., fluticasone) can precipitate iatrogenic Cushing syndrome via CYP3A4 inhibition. Particular vigilance is required in paediatric congenital HIV patients (PMID 28458904).
Cardiovascular Monitoring: Long-term use of ABC-containing regimens has been associated with elevated cardiovascular risk signals in some cohort studies (PMID 37967231). Periodic lipid, glucose, and blood pressure monitoring is recommended.

Conclusion and Next Steps

Decision: Proceed with Guardrails

Rationale: Multiple large, completed Phase 3 RCTs (PENTA 5, STRIIVING, SWORD-1/2, and IMPAACT programme trials) establish an L1 evidence base for ABC/3TC-containing regimens in both paediatric and adult HIV populations. The underlying NRTI mechanism is directly applicable to congenital HIV-1, and international treatment guidelines (WHO/DHHS) already list ABC/3TC as a preferred backbone. Singapore non-registration is the primary operational barrier rather than a clinical evidence gap.

To proceed, the following is needed:

HLA-B*57:01 pre-screening protocol established for all candidates prior to initiation — non-negotiable safety requirement
Regulatory pathway: Apply to HSA for product registration, or establish a compassionate use / named-patient programme while registration is pending
Paediatric dosing protocol: Confirm weight-band or age-based dosing using WHO/DHHS paediatric HIV guidelines and Triumeq PD® dispersible tablet specifications
Formal MOA data retrieval: Query DrugBank API (DB01048) to complete the mechanistic analysis and fill the current data gap
Package insert review: Obtain originator Ziagen® and Triumeq® package inserts for complete contraindication, warning, and monitoring guidance
Long-term cardiovascular and metabolic monitoring plan for paediatric patients on ABC-containing regimens
DDI screening: Flag all co-medications (especially inhaled corticosteroids if used with ritonavir-boosted backbone) before treatment initiation

⚠️ Disclaimer: This report is for research reference only and does not constitute medical advice. All drug repurposing candidates require clinical validation before application. Clinicians should refer to current package inserts and treatment guidelines for prescribing decisions.

Disclaimer

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