What medication should be added to Biktarvy (bictegravir/emtricitabine/tenofovir alafenamide) for a patient with HIV treatment failure?

Management of HIV Treatment Failure on Biktarvy

Do not simply add a single medication to Biktarvy when treatment failure occurs; instead, construct an entirely new regimen using at least 2 fully active drugs from different antiretroviral classes based on resistance testing. 1

Initial Assessment and Critical First Steps

Before making any treatment changes, you must:

• Confirm true virological failure (HIV RNA >200 copies/mL on 2 consecutive measurements), as isolated blips or low-level viremia between 20-200 copies/mL do not warrant regimen changes 1
• Obtain resistance testing immediately while the patient is still taking Biktarvy, or within 4 weeks of stopping if already discontinued 1
• Review all historical resistance data from any prior genotypes, as archived mutations matter even if not currently detected 1
• Assess adherence thoroughly, including psychosocial circumstances, financial barriers, drug interactions, and supplements that may affect absorption 1

Understanding Biktarvy Failure Context

Virological failure on bictegravir-based regimens is extremely rare in clinical trials, and resistance emergence is uncommon 1. When it does occur:

• The most likely cause is poor adherence rather than true resistance 1
• Case reports document emergence of R263K integrase mutations and M184V NRTI mutations with confirmed failure 2
• The high genetic barrier of bictegravir means failure often indicates significant adherence issues 3, 4

Recommended Salvage Regimens After Biktarvy Failure

If Integrase Resistance is Detected:

Switch to a boosted protease inhibitor (PI) regimen plus 2 NRTIs (with at least 1 fully active based on resistance testing) 1. This represents the evidence-based approach for INSTI failure.

Specific options include:

• Darunavir/ritonavir or darunavir/cobicistat plus 2 active NRTIs 1
• Alternative boosted PIs if darunavir resistance exists 1

If No Integrase Resistance Detected (Adherence-Related Failure):

Dolutegravir 50 mg twice daily plus at least 1 other fully active drug may be effective, particularly if raltegravir or elvitegravir resistance patterns are present but not bictegravir-specific mutations 1

For Multidrug Resistance or Limited Options:

If the patient has extensive multiclass resistance including to INSTIs, novel mechanism agents are required:

• Fostemsavir (attachment inhibitor) with at least 1 additional active drug - 60% achieved viral suppression at 96 weeks 1
• Ibalizumab (CD4 monoclonal antibody) administered IV every 2 weeks with optimized background therapy - 50% achieved undetectable viral loads at 12 months 1
• Lenacapavir (capsid inhibitor) ideally combined with another fully active agent 1

These should be used in combination to achieve 2 fully active drugs whenever possible 1.

Critical Principles That Must Be Followed

• Never add a single active drug to the failing Biktarvy regimen - this is explicitly contraindicated and will lead to further resistance 1
• At least 2 fully active drugs from different classes are required for the new regimen 1
• Resistance testing must guide drug selection - use both current and all historical genotypes to construct the resistance profile 1
• Expert consultation is recommended for complex treatment histories or multiclass resistance 1

Special Considerations

Hepatitis B Co-infection:

If the patient has chronic HBV, you must continue tenofovir-based therapy (either TDF or TAF) or provide alternative HBV suppressive therapy to prevent hepatitis flare 5

Renal Function:

Assess kidney function to determine appropriate NRTI backbone and whether dose adjustments are needed 5

Drug-Drug Interactions:

Review all concomitant medications, as interactions may have contributed to subtherapeutic levels 1

Common Pitfalls to Avoid

• Do not restart Biktarvy after confirmed virological failure with resistance - this guarantees treatment failure 1
• Do not switch based on isolated viral blips <1000 copies/mL that return to undetectable 1
• Do not delay resistance testing - obtain it while on the failing regimen for optimal mutation detection 1
• Do not assume adherence is adequate without thorough investigation - this is the most common cause of INSTI failure 1

Monitoring After Regimen Change

• HIV RNA at 2-4 weeks to confirm early virologic response 6
• Goal of undetectable viral load by 12-24 weeks from new regimen initiation 6
• Repeat resistance testing if the new regimen fails to guide subsequent therapy 1