Dolutegravir with Tenofovir Without Emtricitabine is NOT Recommended
Dolutegravir combined with tenofovir alone (without emtricitabine or lamivudine) is not a guideline-recommended regimen for HIV treatment. All major guidelines consistently specify that dolutegravir must be paired with two nucleoside reverse transcriptase inhibitors (NRTIs), not just one 1.
Why This Combination is Inadequate
Guideline-Recommended Regimens Always Include Two NRTIs
The International Antiviral Society-USA Panel's most recent recommendations (2020) explicitly list the following dolutegravir-based regimens as recommended initial therapy 1:
- Dolutegravir/abacavir/lamivudine (evidence rating AIa)
- Dolutegravir plus tenofovir alafenamide/emtricitabine (evidence rating AIa)
- Dolutegravir plus tenofovir disoproxil fumarate/emtricitabine (evidence rating AIa)
Notice that every recommended regimen includes both tenofovir AND emtricitabine (or lamivudine) 1. The 2016 and 2018 guidelines similarly specify dolutegravir must be combined with dual-NRTI backbones 1.
The Evidence Base Supports Three-Drug Regimens
All pivotal clinical trials establishing dolutegravir's efficacy used three-drug combinations 1. The FDA label for dolutegravir (Tivicay) explicitly states it is "indicated in combination with other antiretroviral agents" (plural) for HIV-1 treatment 2. Using dolutegravir with only one NRTI has never been studied or validated in clinical trials.
Two-Drug Regimens Require Specific Combinations
While two-drug regimens are now accepted in certain contexts, they involve specific validated combinations 1:
- Dolutegravir/lamivudine (not dolutegravir/tenofovir alone) 1
- Dolutegravir/rilpivirine 1
- Boosted protease inhibitor with lamivudine 1
The GEMINI trials demonstrated non-inferiority of dolutegravir plus lamivudine versus three-drug regimens, with 91% achieving viral suppression at 48 weeks 3. However, this was dolutegravir with lamivudine, not tenofovir alone.
Critical Risks of Using Only One NRTI
Insufficient Viral Suppression
Monotherapy or inadequate dual therapy dramatically increases the risk of:
- Virologic failure with detectable HIV RNA 1
- Development of resistance mutations to both the integrase inhibitor and the single NRTI 1
- Loss of future treatment options due to cross-resistance 1
Guidelines explicitly state that "monotherapy with boosted PIs or dolutegravir is not recommended" (evidence rating AIIa), and this principle extends to inadequate dual therapy 1.
Resistance Development
Even with dolutegravir's high genetic barrier to resistance, using only one active NRTI creates selective pressure that can lead to:
- Integrase strand transfer inhibitor resistance mutations 1
- NRTI resistance mutations that compromise future regimens 1
- Multi-class resistance limiting salvage options 1
The Correct Approach
Use Guideline-Recommended Three-Drug Regimens
For treatment-naive patients, prescribe 1:
- Bictegravir/tenofovir alafenamide/emtricitabine (evidence rating AIa)
- Dolutegravir/abacavir/lamivudine (evidence rating AIa, requires HLA-B*5701 testing)
- Dolutegravir plus tenofovir alafenamide/emtricitabine (evidence rating AIa)
If Emtricitabine is Unavailable
If emtricitabine cannot be obtained, lamivudine is an acceptable substitute as it is pharmacologically similar and recommended in guidelines 1. The regimen would be dolutegravir plus tenofovir disoproxil fumarate/lamivudine, which maintains the essential three-drug structure.
Consider Two-Drug Regimens Only in Specific Situations
Two-drug regimens are appropriate only for virologically suppressed patients switching therapy, and only with validated combinations like dolutegravir/lamivudine 1, 4. The D2ARLING trial showed 92% viral suppression with dolutegravir/lamivudine in treatment-naive patients, but this was a two-drug regimen with lamivudine, not tenofovir alone 4.
Common Pitfalls to Avoid
- Never use dolutegravir with only one NRTI as this lacks evidence and violates all treatment guidelines 1
- Do not confuse two-drug regimens (dolutegravir/lamivudine) with inadequate single-NRTI combinations 1, 4
- Always verify the complete regimen includes either two NRTIs or a validated two-drug combination before prescribing 1
- Resistance testing should guide therapy but does not justify using suboptimal drug combinations 1