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DTG+TDF/FTC* is a regimen containing two NRTIs and an INSTI. It is considered a recommended regimen by both the DHHS and the IAS for treatment-naïve patients. This regimen is not specifically discussed in either guideline for treatment-experienced patients, but both guidelines state that DTG has been found to be superior to other INSTIs in studies.

*There is evidence from bioequivalence or relative bioavailability studies that TAF can be substituted for TDF without loss of efficacy and with an improved side effect profile, particularly less impact on kidney function and on bone loss[1]. As such, TAF, an oral prodrug of TDF, is now included (since 2016) as a component of several recommended regimens and first line therapy in both DHHS and IAS guidance. TAF is FDA approved for use in patients with estimated CrCl as low as 30mL/min.

Recommendations for treatment-naive patients

DHHS: As a regimen of an INSTI + 2 NRTIs, TDF/FTC+DTG is a recommended initial regimen for most patients with HIV.

IAS: TDF/FTC+DTG is a recommended regimen for treatment-naïve patients.

Recommendations for treatment-experienced patients

DHHS: In virally suppressed patients, within-class switches from RAL to DTG may be considered if the switch will improve QOL and maintain viral suppression. Recommended between-class switches include replacing an NNRTI or boosted PI with an INSTI.

In cases of confirmed virologic failure, the DHHS does not discuss switching to a regimen of 2 NRTIs + 1 INSTI specifically, but discusses considering a switch to a non-PI-based regimen with more than two fully active agents in cases of poor tolerability or interactions that result in the virologic failure of a PI-based regimen.

IAS: In virally suppressed patients, switching from an older regimen to a simpler single-pill regimen of 2 NRTIs + 1 INSTI may be considered as long as the patient has no resistance or mutations that would result in virologic failure. However, a regimen of DTG + TDF/FTC is not a single-pill regimen and is not specifically discussed for virally suppressed patients by the IAS.

In cases of virologic failure, the IAS does not have any specific recommendations, but notes that in treatment-experienced patients, DTG was found to be superior to RAL.

Other Considerations


  • Can lead to renal and bone toxic effects due to high plasma tenofovir concentrations
  • High daily dose (as compared to TAF)
  • Similar rates of HIV suppression, resistance with virologic failure, and increases in CD4 cell count as TAF


  • DTG has the lowest risk of resistance with virological failure among INSTIs
  • Relatively few drug interactions
  • Can be taken with or without food (but not at the same time as polyvalent cations, which may be found in antacids, laxatives, and mineral supplements; give DTG at least 2 hours before or at least 6 hours after antacids containing polyvalent cations). 
  • DTG may raise serum creatinine due to inhibition of tubular secretion of creatinine without affecting renal glomerular function
  • Possible side effects include insomnia, headache, and (rarely) hypersensitivity reaction


Efficacy in Clinical Trials

Trial Name

Drugs Compared





833 tx-naive

At week 48, the proportion of participants with an HIV-1 RNA level of less than 50 copies per milliliter was significantly higher in the ABC/3TC/DTG group than in the TDF/FTC/EVF group (88% vs. 81%).  Was due primarily to discontinuations because of adverse events (2% in the ABC/3TC/DTG group and 10% in the TDF/FTC/EVF group). At week 144, ABC/3TC/DTG remained superior (71% vs 63% viral suppression) [2] [3] [4]



495 tx-naive women

At 48 weeks, ABC/3TC/DTG was superior in terms of virologic suppression (82% vs 71%). There were fewer virological nonresponses and fewer discontinuations due to adverse events in the ABC/3TC/DTG arm [5]


2 NRTIs plus DTG or DRV/r

484 tx-naive

At 48 weeks, DTG outperformed DRV/r (viral suppression 90% vs 83%). Discontinuation due to adverse effects was higher in the DRV/r group than the DTG group (2% vs 4%, respectively), which contributed to the difference in the response rate. DTG continued to outperform DRV/r at 96 weeks (viral suppression 80% vs 66%) [6][7]


2 NRTIs plus DTG or RAL

822 tx-naive

At 48 and 96 weeks, once-daily DTG was non-inferior to twice-daily RAL (88% vs 85% viral suppression at 48 weeks, and 81% vs 76% at 96 weeks), with a similar safety profile[8] [9]


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