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This is a generic educational information sheet for 1 NRTI + 1 INSTI regimens.


Use of 1 NRTI + 1 INSTI regimens is becoming supported by emerging evidence for using this regimen as a treatment simplification for virologically suppressed patients, and in ART naive patients as it offers cost or toxicity advantages over 3-drug regimens.Dual-treatment studies of 1 NRTI + 1 INSTI have primarily included DTG; success with RAL is inferred from that data, but should be considered with caution as RAL has lower barrier to resistance than DTG.  The majority of data has been with DTG+3TC; anticipated efficacy of DTG+other NRTI's is inferred.

Recommendations for Treatment-Naïve Patients

DHHS:1INSTI +1NRTI is discussed in the context of patients who cannot take ABC, TAF, TDF.  It may be considered to minimize toxicity or costs.  In the Gemini trials, at Week 48, the 2-drug regimen was noninferior to DTG + FTC/tenofovir disoproxil fumarate (TDF) (91% vs 93% with HIV-1 RNA < 50 copies/mL, respectively); of note, viral load at entry was capped at 500,000 and this strategy may not be appropriate for those at much higher viral loads.IAS: Initial 2-drug regimens are only recommended for consideration in the rare situations in which a patient cannot take ABC, TAF, or TDF. Given that there are not any adequately-powered studies of initial therapy for 1 NRTI + 1 INSTI regimens, efficacy of these regimens is inferred from other clinical trials. IAS does acknowledge the promising PADDLE trial results, but considers the trial to be too small to make a formal recommendation of 1 NRTI + 1 INSTI regimens for treatment-naïve patients[1]. IAS recommends DTG over RAL among INSTI drugs, as DTG has been found to be noninferior to RAL in treatment-naïve patients, whereas it was found to be superior to RAL in treatment-experienced patients.

Recommendations for Treatment-Experienced Patients

DHHS: In virally suppressed patients, the DHHS guidelines discuss the results of the Lamidol trial which evaluated DTG+3TC as a maintenance strategy in suppressed patients with no history of NRTI, INSTI, or PI resistance. 90% of patients achieved and maintained viral suppression, but given this is a single arm study, it was felt that additional evidence is still needed.   In cases of confirmed virologic failure, the DHHS recommends that patients be put on a regimen with at least two to three active drugs and does not specifically discuss this regimen.

IAS: The IAS does not specifically recommend this regimen for treatment-experienced patients in cases of confirmed virologic failure. However, in virally suppressed patients, they recommend to consider switching patients on older regimens to a variety of simplified regimens (i.e. from use of old NRTIs as they have long-term toxic effects, or older PIs that have higher pill burdens and are more metabolically toxic), but do not specifically recommend any 2 drug regimens.

Other Considerations


  • Lowest risk of resistance with virological failure among INSTIs
  • Relatively few drug interactions
  • Can be taken with or without food (but not with polyvalent ions, which may be found in antacids, laxatives, and mineral supplements)
  • May raise serum creatinine 
  • Possible side effects include insomnia, headache, and (rarely) hypersensitivity reaction


  • Must be taken twice daily, although a once daily dose has shown similar efficacy in a recent trial, but there is not enough data to recommend this[2].
  • Should not be taken with polyvalent cations, which may be found in antacids, laxatives, and mineral supplements
  • Possible side effects include creatine kinase elevation, myositis, rhabdomyolysis, and (rarely) severe skin reactions and systemic hypersensitivity reactions


Efficacy in Clinical Trials


Trial Name

Drugs Compared


Study Results


3TC+DTG (1 arm)

20 tx-naive

At week 48, 90% (18 of 20) achieved viral suppression. The combination was well tolerated through week 48, and all adverse events were reported in the first week of therapy [1].



104 tx-experienced

101/104 (97%) of patients who switched from triple ART to DTG+3TC maintained therapeutic success through 40 weeks of dual therapy [unpublished; Joly V, et al CROI 2017 Abstract 458][3]   

ACTG A5353


120 Tx naive

At week 24, 90% had HIV RNA<50copies/ml (with similar response in those with high and low baseline VL). Three participants with suboptimal adherence experienced virologic failure, one with INSTI mutation.[4]



719 vs 722 tx-naive, with Vl<500,000

At week 48, 91% and 93% were virally suppressed in the 2 drug and 3 drug arms, respectively, in the pooled analysis of GEMINI 1 and 2, and met non-inferiority margin [5][6]


DTG+3TC (n=44) vs 3 drug ART (n=45)

44 vs 45 suppressed patients with no hx of failure or known NRTI or INSTI mutations and no HBV

At week 24 and 48, 93 vs91% and 91 vs 89% were suppressed for the DTG+3TC vs 3-drug ART regimens, respectively.[7]


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