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TAF/FTC/RPV* is a regimen containing two NRTIs and an NNRTI, and is dosed as one pill taken once a day. It is considered an alternative regimen by the DHHS and a recommended regimen for patients who cannot take an INSTI by the IAS. In certain circumstances, this regimen is considered in treatment-experienced patients, as there is data to switch from EFV to RPV[1], boosted PI to RPV [2].

*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[3]. 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 is an alternative regimen for treatment-naive patients with an HIV RNA <100,000 copies/mL and a CD4 count of > 200 cells/mm3. It is effective and tolerable, but has potential disadvantages, limitations for use, and/or less supporting data from RCT than recommended regimens.

IAS: TAF/FTC/RPV is a recommended initial regimen for individuals in whom an INSTI is not an option. RPV-containing regimens have low risk of rash and are the smallest single-pill regimens available, but have limitations in pts with high Vl or low CD4.

Recommendations for treatment-experienced patients      

DHHS: In virally suppressed patients, a switch to this regimen is only mentioned for consideration in cases where a switch would maintain viral suppression and where there is no resistance to any components in the regimen, in this case, NNRTIs. In certain circumstances a boosted PI can be replaced with RPV. Within the NNRTI class, switching from EFV to RPV is recommended 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. In cases of confirmed virologic failure, the DHHS does not currently address switching to this regimen because of NNRTI-based regimen failure.

IAS: There is no explicit recommendation to switch to this type of regimen in the IAS guidelines. However, they recommend to consider switching patients on older regimens to a variety of single-pill regimens, including RPV/FTC/TDF. Situations in which patients should be recommended a switch include use of old NRTIs as they have long-term toxic effects, or older PIs that have higher pill burdens and are more metabolically toxic than DRV or ATV. 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 [3]
  • Should not be used in patients with CrCl<30


  • Smallest tablet among the single-pill regimens
  • Approved for use in patients with pre-treatment viral loads <100,000 copies/mL and CD4 count >200 cells/mm3
  • Must be taken with a high-calorie meal (at least 390 kcal)
  • Interacts with many other drugs
  • Contraindicated with PPIs, use with caution with H2 antagonists or antacids
  • Can prolong the QTc
  • Lowest risk of rash among NNRTI-based therapies, and low risk of metabolic adverse effects
  • Possible side effects include depressive disorders and suicidality


Efficacy in Clinical Trials

Trial Name Drugs Compared Participants Study Results
STaR TDF/FTC/RPV vs. TDF/FTC/EFV 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%]). [4] [5].
ECHO and THRIVE 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). [6] [7] [8] .
N/A EFV/FTC/TDF vs RPV/FTC/TDF 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[1].
N/A 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[2].


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