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EVG/c/TDF/FTC* is a regimen containing two NRTIs, an INSTI, and a PK enhancer. It is available in a fixed dose combination and is prescribed as one pill taken once daily. This regimen is recommended by both the DHHS and the IAS for treatment-naive patients and is recommended for consideration for treatment-experienced patients. The cobicistat component of the regimen leads to interactions with many other medications.

 *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 (2018): EVG/c/TDF/FTC  was moved from being considered recommended for most individuals, to  recommended for initial treatment regimen in certain clinical situations.  This change was made "because these combinations include COBI" which increases the likelihood of drug-drug interactions. EVG also has a lower barrier to resistance than DTG and BIC.

IAS(2018): EVG/c/TDF/FTC is a recommended regimen for treatment-naïve patients in whom generally recommended regimens cannot be used or are not available.

 Recommendations for treatment-experienced patients

DHHS: In virally suppressed patients, within-class switches from RAL to EVG/c 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 recommends 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 like this one, EVG/c/FTC/TDF, may be considered as long as the patient has no resistance or mutations that would result in virologic failure. In cases of virologic failure, the IAS does not have any specific recommendations, but notes that in treatment-experienced patients, EVG was found to be noninferior 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


  • Must be taken with food (but not at the same time as polyvalent cations, which may be found in antacids, laxatives, and mineral supplements; separate administration of EVG/c and polyvalent ion antacids by more than 2 hours)
  • Contraindicated in pregnancy
  • Cobicistat may raise serum creatinine due to inhibition of tubular secretion of creatinine without affecting renal glomerular function
  • Interacts with many other drugs; check for interactions before prescribing
  • Possible side effects include diarrhea, nausea, headache, and fatigue


Efficacy in Clinical Trials

Trial Name

Drugs Compared


Study Results



1733 tx-naive

TAF/FTC/EVG/c was non-inferior to TDF/FTC/EVG/c (92% viral suppression in the TAF group and 90% in the TDF group) Patients given TAF/FTC/EVG/c had significantly smaller mean serum creatinine increases than those given TDF/FTC/EVG/c (0·08 vs 0·12 mg/dL), significantly less proteinuria (median % change -3 vs 20), and a significantly smaller decrease in bone mineral density at spine (mean % change -1·30 vs -2·86) and hip (-0·66 vs -2·95) at 48 weeks [2].



757 tx-naive

At 48 weeks, TDF/FTC/EVG/c was non-inferior to TDF/FTC/EFV (88% viral suppression vs. 84%). Proportions of patients discontinuing drugs for adverse events did not differ substantially (4% in the TDF/FTC/EVG/c group vs 5% in the TDF/FTC/EFV group). Similar findings were also seen at 96 weeks (84% viral suppression vs. 82%) and 144 weeks ( 80% viral suppression vs. 75%)  [3] [4] [5].



708 tx-naive

At 48 weeks, TDF/FTC/EVG/c was non-inferior to TDF/FTC+ATV/r (90% viral suppression vs. 87%, respectively).   Proportions of patients discontinuing drugs for adverse events did not differ substantially (4% of TDF/FTC/EVG/c vs 5% of TDF/FTC+ATV/r). Similar findings were also seen at 96 weeks (83% viral suppression vs. 82%) and 144 weeks (78% viral suppression vs. 75%)  [6] [7] [8].



575 tx-naïve women

At 48 weeks, 87% of the women in the TDF/FTC/EVG/c group achieved viral suppression, vs. 81% of the women in the TDF/FTC+ATV/r group. 5 women in the in the TDF/FTC/EVG/c group discontinued due to adverse events, compared to 19 women in the TDF/FTC+ATV/r group[9]


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