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EFV+TAF/FTC* is a regimen containing two NRTIs and an NNRTI, dosed as one pill taken once a day. It is classified as an alternative regimen by the DHHS and is a recommended regimen for patients who cannot take an INSTI by the IAS. It has interactions with many other medications, and possible CNS side effects.

*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+EFV is classified as a recommended initial treatment regimen in certain clinical situations for patients with an HIV RNA <100,000 copies/mL and a CD4 count of > 200 cells/mm3.  Due to the availability of regimens with fewer treatment-limiting adverse events and noninferior or superior efficacy, INSTI + 2 NRTI regimens are recommended for most.

IAS: TAF/FTC+EFV is not discussed in the IAS guidelines. However, EFV/TDF/FTC is a "recommended initial regimen for individuals in whom an INSTI is not an option." This regimen has the benefit of high efficacy in patients with baseline HIV Vl>100,000 and there is wide global availability and extensive experience; disadvantages include high rates of neuropsychiatric side effects. 

Recommendations for treatment-experienced patients

DHHS: The DHHS does not mention use of this regimen for treatment-experienced patients. Mentions of switches to an NNRTI-based regimen in virally suppressed patients, advise considering a switch from EFV to RPV in certain circumstances. In cases of confirmed virologic failure, the DHHS does not currently recommend switching to an NNRTI + 2 NRTI regimen at this time.

IAS: There is no explicit recommendation to switch to this type of regimen (2 NRTI + 1 NNRTI) in the IAS guidelines in the setting of treatment failure or for those that are virally suppressed. However, they suggest that when virally suppressed, there may be consideration for switching patients on older regimens to a variety of single-pill regimen. Situations in which patients should be recommended a switch include use of old NRTIs as they have long-term toxic effects, or older drugs that have higher pill burdens and are more metabolically toxic.

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


  • Widely available globally 
  • Available as a fixed-dose combination tablet of FTC/TDF/EFV, but no single tablet form available with TAF
  • High efficacy in patients with baseline HIV RNA > 100,000 copies/mL
  • Extensive experience in patients with TB
  • Interacts with many other drugs, including methadone
  • Consider avoiding in patients with QTc prolongation
  • May be associated with suicidality
  • Use with caution in patients with HIV-associated dementia
  • Possible side effects include rash, elevation in LDL cholesterol and/or triglycerides, depression, abnormal dreams, dizziness, and headache


Efficacy in Clinical Trials

Trial Name

Drugs Compared


Study Results

ACTG 5202

2 NRTIs plus EFV or ATV/r

463 tx-naive patients

EFV was comparable to ATV/r with respect to virological response when each was given with either TDF/FTC or ABC/3TC [2].

GS 102

FTC/TDF/EFV was non-inferior to EVG/c/TDF/FTC


At 144 weeks, EFV was non-inferior with respect to study discontinuation [3].



833 tx-naive

At 48 weeks, a DTG-based regimen was superior to EFV with regards to viral suppression [4].



566 tx-naive

At 48 weeks, RAL was noninferior to EFV. At 4 and 5 years, RAL was superior to EFV, in part because of more frequent discontinuations due to adverse events in the EFV group [5][6][7].



786 tx-naive

At week 48 TDF/FTC/RPV was noninferior to TDF/FTC/EFV (viral suppression of 86% versus 82%). TDF/FTC/RPV was more efficacious than TDF/FTC/EFV in persons with baseline HIV RNAs of ≤ 100,000  copies/ml (89% viral suppression versus 82%).  For participants with baseline HIV-RNAs between 100,000-500,000 copies/mL, the virologic failure rate in the TDF/FTC/RPV and TDF/FTC/EFV arms were 10% and 8.5% (not statistically significant). For those with a HIV RNA of ≥ 500,000 copies/mL it was 25% and 16% (not statistically significant). More emergent resistance occurred in the TDF/FTC/RPV arm (4% versus 1%). TDF/FTC/PRV had fewer discontinuations because of adverse events (2.5 vs 9%). These findings held at 96 weeks (overall viral suppression 78% for TDF/FTC/RPV versus 72% for TDF/FTC/EFV; higher efficacy of TDF/FTC/RPV in persons with HIV RNA <100,000 copies/mL [79% viral suppression versus 72%]; fewer discontinuations in the TDF/FTC/RPV group [3% versus 11%]). [8] [9].


2 NRTIs plus RPV or EFV

1368 tx-naive

At week 48 the RPV arm was noninferior to the EFV arm (overall 84% viral suppression versus 82%).  Virologic failure occurred in 9% of patients in the RPV arm and 5% in the EFV arm. Discontinuation due to adverse events occurred in 3% of the RPV arm and 8% of the EFV arm. In participants with virologic failure, NNRTI and NRTI resistance was more frequently identified in the RPV arm. Also, in the RPV arm the rate of virologic failure was greater in those with pre-treatment CD4 counts <200 cells/mm3. These findings held at 96 weeks (overall viral suppression of 77% in both arms; viral suppression of 83% and 80% for persons with baseline HIV RNA <100,000 copies/mL; viral suppression of 60% versus 75% in persons with baseline HIV RNA levels of >500,000 copies/mL; 4% discontinuation due to adverse events in the RPV arm and 8% in the EFV arm; NNRTI and NRTI resistance was more frequently identified in the RPV arm in persons with virologic failure). [10] [11] [12] . 


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