Aristada
Aristada
Generic Name
Aristada
Mechanism
- Abacavir – a *carbocyclic nucleoside analogue* that is intracellularly phosphorylated to abacavir‑triphosphate. It competitively inhibits reverse transcriptase (RT) by mimicking ATP, leading to premature termination of the viral RNA–DNA chain.
- Lamivudine – a *dideoxycytidine analogue* phosphorylated to lamivudine‑triphosphate, which also competes with the natural substrate and causes chain termination.
- The dual NRTI regimen exerts synergistic activity, reduces the likelihood of resistance development, and improves viral suppression rates.
Pharmacokinetics
| Parameter | Abacavir | Lamivudine |
| Absorption | Oral, ~100 % bioavailability, peak at ~30 min | Oral, ~100 % bioavailability, peak at ~30 min |
| Distribution | Low protein binding (~10 %) | Low protein binding (~0–6 %) |
| Metabolism | Primarily oxidized by CYP2C19 (minor hepatic) | Minimal hepatic metabolism; glucuronidation via UGT1A3 |
| Excretion | Hepatic (~20 %) and renal (~70 %) | Renal (~90 %) |
| Half‑life | 30–40 min (active metabolite) | 5–7 h |
| Steady‑state | ~5–7 days | ~7 days |
Both agents are taken once daily as a single tablet; no dose adjustment is required to achieve steady state.
Indications
- First‑line or maintenance therapy for HIV‑1–infected adults and children ≥ 4 years (≥ 15 kg) who are treatment‑naïve or switching from another regimen.
- Acceptable in patients with mild to moderate renal dysfunction (creatinine clearance ≥ 50 mL/min); not recommended in severe renal impairment.
Contraindications
- Hypersensitivity to abacavir (e.g., rash, fever, or malaise after ≥ 2 days of therapy); also contraindicated if cross‑reactive to other abacavir or norfloxacin‑containing drugs.
- HLA‑B*5701 allele carriers – absolute contraindication due to severe hypersensitivity reaction risk.
- Severe renal or hepatic disease (especially cirrhosis) may necessitate dose adjustment or alternative therapy.
- Lamivudine – avoid in patients with significant renal impairment (eGFR < 15 mL/min) due to accumulation.
Warning: Monitor for drug‑induced liver injury; patients with pre‑existing hepatic disease should be followed closely.
Dosing
| Population | Dose | Frequency |
| Adults, ≥ 4 weeks | 200 mg abacavir / 150 mg lamivudine (fixed‑dose tablet) | Once daily |
| Children (≥ 4 kg) | Same fixed dose; weight‑based calculations not required due to fixed dosing | Once daily |
• Take with or without food.
• If a dose is missed, skip the missed dose and resume the next scheduled dose; do not double‑dose.
Adverse Effects
Common (≥ 1 % of patients)
• Nausea, vomiting, abdominal pain
• Headache, dizziness
• Rash (occasionally mild)
• Anemia, thrombocytopenia (rare)
Serious (≤ 0.1 %)
• Abacavir hypersensitivity reaction: fever, rash, bronchospasm, dyspnea, eosinophilia (often > 2 days) → immediate discontinuation.
• Hepatotoxicity (elevated ALT/AST ≥ 5× ULN)
• Renal tubular acidosis (rare) – monitor serum creatinine and bicarbonate.
Monitoring
| Test | Frequency | Rationale |
| Baseline CBC, LFTs, renal panel | Before initiation | Detect pre‑existing cytopenias or organ dysfunction |
| HLA‑B*5701 testing | Prior to therapy | Prevent hypersensitivity |
| CBC, LFTs, creatinine | Every 3–6 months | Monitor for bone marrow suppression or organ injury |
| HIV viral load & CD4 count | Every 3–6 months | Assess therapeutic response |
| Pregnancy test (women of childbearing potential) | Prior to initiation | Avoid teratogenic risk |
Clinical Pearls
- HLA‑B*5701 screening is mandatory; a negative result *significantly* lowers abacavir hypersensitivity risk.
- Avoid concomitant use of high‑dose tenofovir – may increase the risk of renal toxicity when combined with lamivudine.
- Immune reconstitution inflammatory syndrome (IRIS) can unmask underlying opportunistic infections soon after therapy initiation; monitor symptomatic patients closely.
- In elderly patients (≥ 65 years), begin with standard dosing but check renal function every 3–6 months, as renal clearance naturally declines.
- Drug–drug interactions: abacavir is a CYP2C19 inhibitor; consider dose adjustments for drugs spanning this pathway (e.g., clopidogrel).
- Pediatric pharmacodynamics: Despite fixed dosing, the weight‑to‑dose ratio mirrors that of the individual agents, thus ensuring optimal plasma concentrations across age groups.
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• References
1. Clinical Infectious Diseases. “Abacavir‑Lamivudine Combination Therapy for HIV‑1.” 2022.
2. FDA prescribing information for Aristada, 2023 update.
3. Pharmacologic Principles for Medical Students, 5th ed., Section 10.3.
*Aristada* offers a convenient once‑daily regimen with a well‑characterized safety profile, making it a cornerstone for HIV‑1 therapeutic strategies.