What are the recommended alternative HIV‑1 regimens for switching from dolutegravir (DTG) due to contraindication, intolerance, or drug–drug interaction?

Alternative HIV-1 Regimens When Switching from Dolutegravir

For virologically suppressed patients switching from dolutegravir due to contraindication, intolerance, or drug-drug interaction, bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) is the preferred alternative, as it maintains the integrase inhibitor backbone with similar efficacy and tolerability. 1

Primary Alternative Regimens by Clinical Scenario

For Drug-Drug Interactions (Especially Rifampin for Active TB)

When dolutegravir cannot be used due to rifampin co-administration or patient unwillingness to take twice-daily dosing:

• Efavirenz 600 mg once daily plus 2 NRTIs (tenofovir/emtricitabine or lamivudine) is the preferred alternative, as it requires no dose adjustment with rifampin 1, 2
• Raltegravir 800 mg twice daily plus 2 NRTIs is an alternative integrase inhibitor option compatible with rifampin 1
• Boosted protease inhibitors should only be used if efavirenz or raltegravir are not options, and require substituting rifabutin 150 mg daily for rifampin 1, 2

Critical caveat: Bictegravir cannot be used with rifampin due to severe drug-drug interactions 1, 2. The two-drug regimen dolutegravir/lamivudine is also contraindicated with rifampin 2.

For Intolerance or Contraindication (Without Drug-Drug Interaction Concerns)

When switching virologically suppressed patients without resistance:

• Bictegravir/emtricitabine/tenofovir alafenamide maintains viral suppression above 90% when switching from other integrase inhibitor regimens 1
• Dolutegravir/rilpivirine is an alternative two-drug regimen that maintained virologic suppression for 2 years with improvements in bone mineral density and kidney function 1
• Darunavir/cobicistat/emtricitabine/tenofovir alafenamide is an option for those requiring a boosted protease inhibitor backbone 1

For Patients with Prior Treatment Failure or Resistance

When NRTI resistance is present but no integrase inhibitor resistance:

• Bictegravir/emtricitabine/tenofovir alafenamide can be used regardless of likely prior NRTI resistance, provided there is no history of integrase inhibitor resistance 1
• Dolutegravir plus tenofovir/emtricitabine maintains efficacy even with NRTI resistance mutations, though closer monitoring is warranted 1
• Switching to NNRTI or first-generation integrase inhibitor regimens (raltegravir or elvitegravir) plus 2 NRTIs is not recommended in the presence of NRTI resistance due to increased risk of virologic failure 1

Important monitoring: Patients with NRTI resistance who switch to dual NRTI plus dolutegravir or bictegravir regimens should have viral load checked at 1 month, then every 3 months for the first year 1.

Alternative Two-Drug Regimens

For patients seeking simplification or tenofovir-sparing options:

• Dolutegravir/lamivudine maintains viral suppression in patients without prior virologic failure, NRTI resistance, or hepatitis B co-infection 1
• Long-acting cabotegravir plus rilpivirine (monthly or every 8-week injections) is noninferior to continuing stable oral regimens, with rates of viral suppression approaching 95% 1

Critical caveat: Long-acting cabotegravir/rilpivirine requires excellent adherence to injection schedules, as missed doses can lead to prolonged subtherapeutic levels and resistance development 1. This regimen should not be used in patients with chronic hepatitis B unless HBV treatment is continued separately 1.

Regimens to Avoid When Switching from Dolutegravir

The following cannot replace dolutegravir in specific contexts:

• With rifampin: Bictegravir, dolutegravir/lamivudine two-drug regimen, doravirine, elvitegravir/cobicistat combinations, long-acting cabotegravir/rilpivirine, and rilpivirine-containing regimens 2
• In pregnancy: Cobicistat-boosted regimens (including darunavir/cobicistat combinations) achieve inadequate plasma levels 3
• With hepatitis B co-infection: Any tenofovir-sparing regimen (dolutegravir/lamivudine, dolutegravir/rilpivirine, long-acting cabotegravir/rilpivirine) unless separate HBV treatment is provided 1, 4

Post-Switch Monitoring Protocol

Regardless of the alternative regimen selected:

• Check HIV-1 RNA at 1 month post-switch to confirm maintained viral suppression 1, 4
• Monitor viral load every 3 months for the first year, then at least every 6 months if stable 4, 3
• Assess renal function (serum creatinine, eGFR) at baseline and periodically, particularly with tenofovir-containing regimens 4
• Review complete antiretroviral treatment history to identify any prior virologic failures or resistance testing results before switching 1, 4

Common Pitfalls to Avoid

• Never assume all integrase inhibitors behave similarly with rifampin: Dolutegravir requires twice-daily dosing with rifampin, raltegravir requires 800 mg twice daily, but bictegravir cannot be used at all 1, 2
• Do not overlook hepatitis B co-infection status: Switching to tenofovir-sparing regimens without addressing HBV can lead to hepatitis flares 1, 4
• Avoid switching if documented integrase inhibitor resistance exists: Both dolutegravir and bictegravir rely on integrase inhibition, so prior resistance limits alternative options 4
• Do not use standard once-daily dolutegravir dosing with rifampin: This results in subtherapeutic levels and treatment failure; 50 mg twice daily is required 1, 2