Dolutegravir-Based HIV Treatment Regimens

Guideline-Recommended Regimens

The International Antiviral Society-USA Panel recommends dolutegravir-based regimens, including dolutegravir/abacavir/lamivudine, dolutegravir plus tenofovir alafenamide/emtricitabine, and dolutegravir plus tenofovir disoproxil fumarate/emtricitabine, as initial therapy with an evidence rating of AIa 2, 3
The American College of Physicians and other guideline societies consistently specify that dolutegravir must be paired with two nucleoside reverse transcriptase inhibitors (NRTIs), not just one 1, 2, 3

All pivotal clinical trials establishing dolutegravir's efficacy used three-drug combinations, and the FDA label for dolutegravir explicitly states it is "indicated in combination with other antiretroviral agents" (plural) for HIV-1 treatment 1, 4

Monotherapy or inadequate dual therapy dramatically increases the risk of virologic failure, development of resistance mutations, and loss of future treatment options due to cross-resistance 3
Using only one active NRTI creates selective pressure that can lead to integrase strand transfer inhibitor resistance mutations, NRTI resistance mutations, and multi-class resistance limiting salvage options 3

For treatment-naive patients, guideline-recommended three-drug regimens include bictegravir/tenofovir alafenamide/emtricitabine, dolutegravir/abacavir/lamivudine, and dolutegravir plus tenofovir alafenamide/emtricitabine, all with an evidence rating of AIa 2, 3
If emtricitabine is unavailable, lamivudine is an acceptable substitute as it is pharmacologically similar and recommended in guidelines 1, 2, 3
Two-drug regimens, such as dolutegravir/lamivudine, are only appropriate for virologically suppressed patients switching therapy, and only with validated combinations 3, 5