Can a patient with HIV (Human Immunodeficiency Virus) who is stable on carbamazepine (Tegretol) 400 mg twice daily (bid) for seizure control be started on Biktarvy (bictegravir/emtricitabine/tenofovir alafenamide)?

Biktarvy Should NOT Be Started in This Patient on Carbamazepine

Do not initiate Biktarvy (bictegravir/emtricitabine/tenofovir alafenamide) in a patient stable on carbamazepine 400 mg twice daily due to a clinically significant drug-drug interaction that will result in subtherapeutic bictegravir levels and high risk of virologic failure. 1

The Critical Drug Interaction

Carbamazepine is a potent inducer of CYP3A4 enzymes, which will dramatically reduce bictegravir concentrations, leading to treatment failure. 2 The 2025 International Antiviral Society-USA guidelines explicitly state that Biktarvy is not recommended with rifampin (another potent enzyme inducer) due to inadequate data and drug-drug interactions 1, and this same principle applies to carbamazepine, which has similar enzyme-inducing properties.

• Real-world therapeutic drug monitoring data demonstrate that integrase inhibitors like dolutegravir (which shares similar metabolic pathways with bictegravir) show 83% reductions in trough concentrations when co-administered with carbamazepine or oxcarbazepine 2
• These dramatically reduced antiretroviral levels fall well below the therapeutic threshold needed to maintain viral suppression 2

Recommended Alternative Antiretroviral Regimens

The preferred approach is to select an antiretroviral regimen with minimal interaction potential with carbamazepine:

First-Line Alternative: Darunavir-Based Regimen

• Darunavir/ritonavir (or cobicistat) plus tenofovir alafenamide/emtricitabine is the recommended alternative 3
• Real-world data show that darunavir trough concentrations remain within therapeutic ranges when co-administered with carbamazepine, unlike other antiretrovirals 2
• Darunavir has a high barrier to resistance, making it particularly suitable when drug interactions are a concern 3

Second-Line Alternative: Adjust the Antiepileptic Drug

If changing the antiretroviral regimen is not optimal, consider switching from carbamazepine to a non-enzyme-inducing antiepileptic drug:

• Levetiracetam is the preferred alternative due to minimal drug interactions, broad-spectrum activity, and favorable side effect profile 4
• Lacosamide, gabapentin, or pregabalin are also suitable alternatives for partial-onset seizures 4
• Valproic acid or lamotrigine can be considered if the above options are not suitable 5, 4

Critical Pitfalls to Avoid

Never assume that therapeutic drug monitoring alone can salvage this combination:

• While TDM can detect subtherapeutic levels, the magnitude of the interaction is so severe that dose adjustments of bictegravir are unlikely to overcome the enzyme induction 2
• Historical case reports document complete antiretroviral treatment failure with development of resistance mutations when protease inhibitors were combined with carbamazepine despite attempts at monitoring 5

Do not use other integrase inhibitors as simple substitutes:

• Dolutegravir shows similar dramatic reductions (83% decrease) in concentrations with carbamazepine 2
• Elvitegravir/cobicistat combinations would face even more severe interactions 3
• Raltegravir has not been adequately studied with carbamazepine but likely faces similar issues 4

Clinical Decision Algorithm

1. Is the patient treatment-naive or treatment-experienced?

   • If treatment-naive: Start darunavir/ritonavir + TAF/FTC 3
   • If treatment-experienced: Assess resistance profile and consider darunavir-based regimen 3

2. Is seizure control stable and well-established?

   • If yes and seizure-free >2 years: Discuss switching to levetiracetam with neurology 4
   • If recent seizures or unstable: Maintain carbamazepine and use darunavir-based ART 2

3. Are there contraindications to darunavir?

   • Consider switching antiepileptic drug to enable use of preferred integrase inhibitor-based regimens 4
   • Valproic acid may be used if newer AEDs unavailable, though side effect profile is less favorable 4

The bottom line: This combination of Biktarvy and carbamazepine represents a high-risk scenario for virologic failure and should be avoided entirely. 1, 2