Makindo Medical Notes

⚠️ Key Safety Point: Abacavir should never be started without testing for the HLA-B*5701 allele. Patients with this gene variant have a high risk of a severe, potentially fatal hypersensitivity reaction. 💔 Use cautiously in those with high cardiovascular risk (10-year risk >20%) or HIV viral load >100,000 copies/mL.

🧠 About

• Abacavir is a nucleoside reverse transcriptase inhibitor (NRTI) used in combination antiretroviral therapy (ART) for HIV infection.
• Commonly combined with lamivudine or dolutegravir in fixed-dose formulations (e.g. Kivexa, Triumeq).
• It remains a useful option when renal impairment limits tenofovir use — but carries added cardiovascular risk.

⚙️ Mechanism of Action

• Abacavir is phosphorylated intracellularly to its active form, carbovir triphosphate.
• It competitively inhibits HIV reverse transcriptase, the enzyme converting viral RNA → DNA.
• Once incorporated into viral DNA, it acts as a chain terminator, halting further synthesis and replication.

🎯 Indications & Dosing

• Used for HIV-1 infection as part of a combination ART regimen.

🧪 Pharmacogenomics & Screening

• ✅ Test for HLA-B*5701 before treatment.
• If positive → do not use abacavir (risk of fatal hypersensitivity).
• Re-exposure after a hypersensitivity reaction is contraindicated.
• Symptoms typically appear within the first 6 weeks: fever, malaise, rash, GI upset, respiratory symptoms — progress rapidly if continued.

🔗 Interactions

• Fewer renal interactions compared with tenofovir.
• May interact with ethanol (increased plasma abacavir levels).
• Otherwise, minimal CYP450 metabolism — fewer hepatic interactions than NNRTIs or protease inhibitors.
• Always review full ART regimen to prevent overlapping toxicities (e.g. lactic acidosis risk with other NRTIs).

⚠️ Cautions

• 💔 Cardiovascular disease: Some data link abacavir with increased risk of myocardial infarction, particularly in those with pre-existing CVD.
• 🫀 Lactic acidosis and hepatic steatosis: Rare but potentially fatal; monitor for unexplained nausea, abdominal pain, or breathlessness.
• 🩸 Liver disease: Use cautiously in patients with hepatitis B or C, or abnormal LFTs.
• 🧬 Immune reconstitution inflammatory syndrome (IRIS): May occur in early ART as immune function improves.

🚫 Contraindications

• Positive for HLA-B*5701 allele.
• Previous abacavir hypersensitivity reaction (even if test negative).
• Moderate to severe hepatic impairment.

💥 Side Effects

• ⚠️ Hypersensitivity reaction (≈5–8%): Fever, rash, malaise, GI and respiratory symptoms — discontinue immediately and never restart.
• 💔 Cardiovascular: Possible increased risk of MI.
• 🫁 Metabolic: Lactic acidosis, hepatic steatosis.
• 🧍‍♂️ Lipodystrophy: Redistribution of fat (central accumulation, limb or facial loss).
• 🦠 Immune reconstitution inflammatory syndrome (IRIS): Worsening of underlying infection as immunity recovers.

📋 Monitoring

💡 Teaching Tip

• Abacavir elegantly illustrates the principle of pharmacogenomic safety screening — a cornerstone of personalised medicine.
• Always remember the triad of major risks: Hypersensitivity → Lactic acidosis → Cardiovascular events.
• In exam questions, if a patient develops rash, fever, or malaise shortly after starting abacavir — the correct action is stop immediately and never restart.

📚 References

• BNF: Abacavir
• BHIVA Guidelines (2024): HIV Treatment in Adults
• Saag MS et al., NEJM 2008;358:568–579 — HLA-B*5701 screening and abacavir hypersensitivity.
• MHRA Drug Safety Update (2012): Abacavir and cardiovascular risk