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TAF/FTC/RPV+DTG* is a regimen containing two NRTIs, an NNRTI, and an INSTI, and is dosed as two pills taken once a day. It does not specifically appear in either the DHHS or IAS guidelines, but regimens of TAF/FTC+DTG or RPV/TAF/FTC are considered recommended regimens by both the DHHS and the IAS. This type of 4 drug regimen is recommended by many experts for patients with M184V mutations as they have increased resistance to FTC and 3TC.

*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-naïve patients

DHHS: TAF/FTC/RPV+DTG is not ranked, but TAF/FTC+DTG is a recommended regimen for most treatment-naive patients with HIV. RPV/TAF/FTC is a recommended initial regimen in certain clinical situations if HIV RNA <100,000 copies/mL and a CD4 count of > 200 cells/mm3. For example, this combination is available as a single pill regimen, and RPV-based pills are smaller in size than other single pill regimens. This may thus be preferable for patients with difficulty tolerating larger medications.

IAS: TAF/FTC/RPV+DTG is not ranked, but TAF/FTC+DTG is one of the INSTI-based regimens that are "optimal for initial therapy". RPV/TAF/FTC is a recommended initial regimen for patients in whom INSTI is not an option.

Recommendations for treatment-experienced patients

DHHS: DTG+RPV/TAF/FTC is not discussed in the guidelines, but, generally speaking, in cases of confirmed treatment failure, patients are recommended to start a regimen with at least 2-3 active agents. The guidelines also mention that there is increasing data that patients who are on at least 3 active drugs achieve a more sustained and improved virologic response as opposed to patients who have fewer active drugs in their regimens. This type of regimen is not discussed in cases of viral suppression. However, within the NNRTI class, switching from EFV to RPV can be considered if there is either an adverse event or because RPV offers a better safety profile, reduced dosing frequency, and lower pill burden, as long as viral suppression is maintained and there is no drug resistance to RPV

IAS: The IAS guidelines do not specifically recommend any regimens for treatment-experienced patients in both cases of virologic failure or suppression and do not discuss this regimen for treatment-experienced patients. The guidelines recommend addressing adherence and drug interactions prior to switching a patient’s regimen in cases of suspected virologic failure. Patients who are taking TDF are recommended to switch to TAF even if they are not experiencing toxic effects, especially if the switch is cost-effective.

Other Considerations


  • Equivalent efficacy to TDF, with improved side effect profile and less impact on kidney function and on bone loss [1]
  • Should not be used in patients with CrCl<30


  • Approved for use in patients with pre-treatment viral loads <100,000 copies/mL and CD4 count >200 cells/mm3
  • Must be taken with food
  • Interacts with many other drugs
  • Should not be taken with a PPI
  • Lowest risk of rash among NNRTI-based therapies, and low risk of metabolic adverse effects
  • Possible side effects include depressive disorders and suicidality.
  • May prolong the QT interval


  • 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 
  • Largest tablet among co-formulated single-pill regimens 
  • Possible side effects include insomnia, headache, and (rarely) hypersensitivity reaction 
  • Use caution in women of child bearing age, based on limited reports of neural tube defects. DHHS recommends documenting negative pregnancy test prior to initiation. Women should be counseled about switching to alternatives if pregnant and within 8 weeks since LMP. [2]


Efficacy in Clinical Trials


Trial Name

Drugs Compared


Study Results



786 tx-naive

At 96 weeks, RPV was non-inferior to EFV overall, superior in patients with pre-ART viral loads ≤100,000 copies/mL, and noninferior in those with pre-ART viral loads >100,000 copies/mL. In patients with pre-ART viral loads >500,000 copies/mL, virologic failure was more common in RPV-treated patients. There were more participants with emergent resistance in the RPV arm [3].


2 NRTIs plus RPV or EFV

1368 tx-naive

RPV was noninferior to EFV overall. Among participants with a pre-ART viral load >100,000 copies/mL, more RPV-treated participants experienced virologic failure. In participants with virologic failure, NNRTI and NRTI resistance was more frequently identified in those treated with RPV. Among the RPV-treated participants, the rate of virologic failure was greater in those with pre-treatment CD4 counts <200 cells/mm3 [4].



49 tx-experienced

100% of patients on RPV/FTC/TDF remained virally suppressed at weeks 12 and 24. At week 48, 93.9% of patients remained suppressed. Switching from EFV/FTC/TDF to RPV/FTC/TDF was found to be safe and effective for patients who are virally suppressed[5].


RPV/FTC/TDF vs baseline PI/r+2NRTIs

476 tx-experienced

RPV/FTC/TDF was found to be noninferior at week 24, with 93.7% of the RPV/FTC/TDF group maintaining viral suppression, while 89.9% of the PI/r+2NRTI group maintained viral suppression. The switch maintained virologic suppression and had a low risk of virologic failure, with improvements in total cholesterol, LDL, and triglycerides[6].


Trial Name

Drugs Compared





833 tx-naive

At 48 weeks, the treatment discontinuation rate was higher in the EFV arm. At week 144, DTG plus ABC/3TC remained superior. [7] [8] [9]



495 tx-naïve women

At 48 weeks, ABC/3TC/DTG was superior. There were fewer virological nonresponses and fewer discontinuations due to adverse events in the 3TC/ABC/DTG arm. [10]


2 NRTIs plus DTG or DRV/r

484 tx-naive

At 48 weeks, DTG outperformed DRV/r. [11]


2 NRTIs plus DTG or RAL

822 tx-naive

At 48 and 96 weeks, DTG was non-inferior to RAL, with a similar safety profile. [12] [13] 


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