Can I combine dolutegravir with other Antiretroviral Therapy (ART) medications?

Dolutegravir Can Be Effectively Combined with Other Antiretroviral Therapy

Yes, dolutegravir can be effectively combined with other antiretroviral therapy (ART) medications and is recommended as part of various combination regimens for HIV treatment. 1

Recommended Dolutegravir-Based Combinations

• Dolutegravir plus 2 nucleoside reverse transcriptase inhibitors (NRTIs) is a recommended first-line regimen, with at least one NRTI being active by genotype 1
• Dolutegravir/lamivudine is recommended as a 2-drug regimen in virologically suppressed patients with no prior virologic failure or transmitted drug resistance 1
• Dolutegravir plus tenofovir alafenamide/emtricitabine or tenofovir disoproxil fumarate/emtricitabine is recommended as a safe option for treatment 1
• For patients with tuberculosis co-infection receiving rifamycin-based treatment, dolutegravir (50 mg twice daily) can be combined with 2 NRTIs 1

Specific Clinical Scenarios for Dolutegravir Combinations

For Treatment-Naïve Patients

• Dolutegravir/lamivudine is recommended as an initial ART regimen (evidence rating: AIa), but with several caveats 1:
  • Not recommended for patients with HIV RNA levels above 500,000 copies/mL
  • Requires confirmation of absence of resistance to either drug before initiation
  • Not recommended for patients with hepatitis B co-infection
  • Less effective in patients with CD4 counts below 200/μL

For Virologic Failure

• Dolutegravir plus at least one fully active agent may be effective in the setting of raltegravir or elvitegravir resistance, with dolutegravir dosed twice daily in this scenario 1
• After initial treatment failure with a non-nucleoside reverse transcriptase inhibitor (NNRTI), dolutegravir plus 2 NRTIs (with at least 1 active by genotype) is recommended 1

For Virologically Suppressed Patients

• Switching from 3-drug regimens to dolutegravir/rilpivirine (evidence rating AIa) or dolutegravir with lamivudine (evidence rating AIIa) is recommended in patients with no prior virologic failure or transmitted drug resistance 1
• Individuals with virologic suppression receiving regimens containing a boosted protease inhibitor and 2 NRTIs can be switched to dolutegravir plus tenofovir/emtricitabine or bictegravir/emtricitabine/tenofovir alafenamide regardless of known or likely prior resistance to the NRTI pair, provided there is no history of integrase strand transfer inhibitor (InSTI) resistance 1

Important Contraindications and Cautions

• Monotherapy with dolutegravir is not recommended (evidence rating AIIa) 1
• Patients with hepatitis B virus co-infection should receive a regimen containing 2 drugs active against hepatitis B (usually tenofovir alafenamide or tenofovir disoproxil fumarate plus lamivudine or emtricitabine) in addition to dolutegravir 1
• A single active agent added to a failing regimen containing dolutegravir is not recommended (evidence rating AIa) 1
• Dolutegravir has drug interactions that may require dosage adjustments or alternative medications 2:
  • When combined with rifampin, carbamazepine, or certain other medications, dolutegravir dosing should be increased to twice daily
  • Medications containing polyvalent cations (e.g., antacids with magnesium or aluminum) should be taken 2 hours before or 6 hours after dolutegravir

Advantages of Dolutegravir in Combination Therapy

• High genetic barrier to resistance with no major treatment-emergent resistance mutations observed in clinical trials 3, 4
• Effective viral suppression when combined with appropriate agents 4, 5
• Generally well-tolerated with fewer adverse events leading to discontinuation compared to some other regimens 4
• Can be effectively combined with many antiretrovirals without dose adjustment, including atazanavir/ritonavir, darunavir/ritonavir, rilpivirine, and others 2

Special Populations

• For pregnant individuals, dolutegravir plus either tenofovir disoproxil fumarate/emtricitabine or tenofovir alafenamide/emtricitabine is recommended as a safe option 1
• For patients with renal impairment, dolutegravir-based regimens may be preferred over tenofovir disoproxil fumarate-containing regimens 6, 7

Dolutegravir's high genetic barrier to resistance, efficacy in combination with various antiretrovirals, and favorable drug interaction profile make it a versatile component of HIV treatment regimens. However, specific combinations should be selected based on prior treatment history, resistance patterns, comorbidities, and potential drug interactions.