Dolutegravir Combination Therapy for HIV Treatment
Dolutegravir can be effectively combined with other antiretroviral therapies (ART) and is recommended as part of both two-drug and three-drug regimens for HIV treatment, with specific combinations determined by patient factors including treatment history, resistance patterns, and comorbidities. 1
Recommended Dolutegravir Combinations
Three-Drug Regimens
- Dolutegravir plus tenofovir disoproxil fumarate/emtricitabine or tenofovir alafenamide/emtricitabine is recommended as a first-line regimen 1, 2
- Dolutegravir plus abacavir/lamivudine is effective but has limited role due to HLA-B*5701 testing requirement and concerns about cardiovascular risk 1, 3
Two-Drug Regimens
- Dolutegravir/lamivudine is recommended as an initial ART regimen (evidence rating: AIa) with several important caveats 1:
- Dolutegravir/rilpivirine is recommended for switching in virologically suppressed patients with no history of resistance 1
- Boosted protease inhibitor with lamivudine is another viable two-drug option 1
Important Considerations and Contraindications
Drug Interactions
- Dolutegravir has minimal drug-drug interactions with medications metabolized through CYP450 pathway 5, 6
- Dose adjustments are required when co-administered with certain medications:
- Efavirenz, fosamprenavir/ritonavir, tipranavir/ritonavir, and carbamazepine require twice-daily dosing of dolutegravir 6
- Medications containing polyvalent cations (antacids with Mg or Al) should be taken 2 hours before or 6 hours after dolutegravir 6
- Calcium or iron supplements can be taken with dolutegravir if taken with food; otherwise, separate by 2 hours before or 6 hours after 6
- Avoid co-administration with oxcarbazepine, phenytoin, phenobarbital, and St. John's wort 6
Special Populations
- For patients with hepatitis B co-infection, dolutegravir should be combined with tenofovir alafenamide or tenofovir disoproxil fumarate to maintain HBV suppression 1, 2
- For pregnant individuals, dolutegravir plus tenofovir disoproxil fumarate/emtricitabine or tenofovir alafenamide/emtricitabine is considered safe 1
Management of Treatment Failure
- For failure of NNRTI-based regimens, dolutegravir plus NRTIs is superior to lopinavir plus NRTIs when at least one active NRTI is available 1
- For failure of integrase inhibitor-based regimens (raltegravir or elvitegravir) with integrase mutations, dolutegravir (50 mg twice daily) with at least one other active drug may be effective 1
- Monotherapy with dolutegravir is not recommended due to higher rates of virologic rebound and resistance development 1, 7
Common Pitfalls to Avoid
- Failing to check for pre-existing resistance before initiating dolutegravir/lamivudine two-drug therapy 1, 4
- Using dolutegravir/lamivudine in patients with hepatitis B co-infection, which can lead to HBV resistance 1
- Not adjusting dolutegravir dosing when co-administered with enzyme-inducing medications 6
- Switching from a boosted PI to dolutegravir in patients with NRTI resistance mutations, which can lead to treatment failure 1
- Using dolutegravir monotherapy, which increases risk of resistance development 1, 7
Monitoring Recommendations
- Viral load assessment is recommended 1 month after starting or switching regimens 1
- Regular monitoring for adherence and tolerability should be performed, especially with newer combinations like dolutegravir/lamivudine 1
- Resistance testing is recommended while the patient is taking a failing ART regimen or within 4 weeks of stopping 1