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TAF/FTC/EVG/c+DRV*+ is a regimen containing two NRTIs, an INSTI, a PI, and a PK enhancer, dosed as two pills taken once a day. It is not routinely used and is only considered in specific circumstances for treatment-naïve and treatment-experienced patients. The DHHS and IAS guidelines do not discuss this regimen for treatment-naïve patients, but the DHHS notes that it has potential as a simplification strategy in virally suppressed patients. In treatment experienced patients, this regimen has shown promising results as a simplification strategy in patients with complicated regimens[1]. Given the promising results of the study, some experts may consider use of this regimen in treatment-naïve patients whose HIV genotypic drug testing results show resistance to multiple ARV drug classes (i.e. NRTI, NNRTI, PI), without resistance to INSTIs.

*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[2]. 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.

+DRV/c was found to be bioequivalent to DRV/r in healthy volunteers[3]. Based on the results of the study, efficacy of DRV/c has been extrapolated from DRV/r data. Therefore, many experts may consider use of DRV/c despite the limited supporting data from clinical trials due to the reduced pill burden. Use of DRV/c is discussed in both the DHHS and IAS guidelines for use in treatment-naïve and treatment-experienced patients. Cobicistat inhibits active tubular secretion of creatinine, which can increase serum creatinine without an effect on renal glomerular function.

Recommendations in treatment-naive patients

DHHS: TAF/FTC/EVG/c+DRV is not ranked, but TAF/FTC/EVG/c and TAF/FTC+DRV/(c or r) are considered  recommended regimens for "most individuals' and 'in certain clinical situations' , respectively, for treatment-naive patients. Additionally, the combination of an INSTI and a PI (RAL + DRV specifically)  is now listed as a 'recommended regimen in certain clinical situations' (for those without CD4<200 or Viral Load >100000). 

IAS: TAF/FTC/EVG/c+DRV is not ranked, but TAF/FTC/EVG/c is one of the INSTI-based regimens that are "optimal for initial therapy".  TAF/FTC+DRV/(c or r) is an alternative regimen.

Recommendations in treatment-experienced patients

DHHS: This regimen is mentioned for treatment of virally suppressed patients who have resistance to at least 2 ARV drug classes without INSTI resistance, given promising results[1]. The DHHS states that the regimen has potential to be a good option for simplification of patients who have complicated rescue regimens.  An RCT of 135 virally suppressed patients on a DRV based regimen and 2 class resistance (who could have a K65R but not a Q151M or T69 insertion) were simplified to EVG/c/FTC/TAF and 97% maintained viral suppression[1].

IAS: This regimen is not discussed in the IAS guidelines for treatment-experienced patients. However, the IAS recommends using a boosted PI in secondline regimens because of the high barrier to resistance.

Other Considerations


  • Equivalent efficacy to TDF, with improved side effect profile and less impact on kidney function and on bone loss [2]
  • Should not be used in patients with CrCl<30


  • Must be taken with food (but not with polyvalent ions, which may be found in antacids, laxatives, and mineral supplements)
  • Contraindicated in pregnancy
  • May raise serum creatinine and reduce estimated CrCl
  • Interacts with many other drugs
  • Possible side effects include diarrhea, nausea, headache, and fatigue


  • Must be taken with food
  • Low risk of virologic failure, even with intermittent use
  • PI boosters (cobicistat and ritonavir) interact with many other drugs 
  • Cobicistat inhibits active tubular secretion of creatinine, which can increase serum creatinine without an effect on renal glomerular function
  • Possible side effects include diarrhea, nausea, and headache


Efficacy in Clinical Trials


Trial Name

Drugs Compared


Study Results




At 48 weeks, FTC/TAF/EVG/c was noninferior in achieving viral suppression, with fewer renal and bone side effects [4].




At 144 weeks, TDF/FTC/EVG/c was noninferior to fixed-dose TDF/FTC/EFV with respect to discontinuation rate [5].




TDF/FTC/EVG/c was noninferior with respect to viral suppression [6].



575 women

At 48 weeks, EVG/c/TDF/FTC had superior efficacy, in part because of a lower rate of treatment discontinuation. 87% of participants on EVG achieved viral suppression, with fewer adverse events and incidents of virological failure than in the ATV group [7].

Study 103


350 tx-naive

At 144 weeks, FTC/TDF/EVGc demonstrated durable efficacy and improved safety [8].


 TAF/FTC/EVG/c+DRV vs baseline regimen

 135 suppressed on DRV, with >=2 class resistance

 At 24 weeks 94% vs 91% in the EVG/c+DRV arm and baseline regimen arms maintained viral suppression, respectively. [1]





Study Participants

Study Results


ABC/3TC+DRV/r (single arm)

67, 48% tx-naive

At 48 weeks, 79% achieved viral suppression [9].


TDF/FTC plus DRV/r or LPV/r 

689 tx-naive

At 92 weeks, DRV/r was superior to LPV/r with respect to virological response. Among participants with baseline HIV RNA levels >100,000 copies/mL, virologic response rates were lower in the LPV/r arm than in the DRV/r arm [10].


2 NRTIs plus DRV/r or DTG

488 tx-naive

At week 96, virologic suppression was significantly greater among those who received DTG. The excess failure observed in the DRV/r group was related to a higher rate of virologic failure among those with a viral load >100,000 copies/mL and more drug discontinuations in the DRV/r group [11].

ACTG A5257

TDF/FTC plus DRV/r, ATV/r, or RAL

1809 tx-naive

Similar virologic efficacy in all three arms, but more participants in the ATV/r group discontinued randomized treatment because of adverse events [12].



2 NRTIs + DRV/c (single arm)

313, 95% tx-naive

At week 48, 81% achieved viral suppression, while 5% discontinued treatment because of adverse events [13].

Study 115

DRV/c vs.DRV/r


DRV/c is bioequivalent to DRV/r in healthy volunteers [3].



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