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DRV/c+TDF/FTC

 

Overview

TDF/FTC+DRV/c*+ is a regimen containing two NRTIs and a boosted PI. It is considered a recommended regimen by the DHHS "in certain clinical situations" and a recommended regimen for patients who cannot take an INSTI by the IAS. DRV/c is as effective as DRV/r and has a lower pill burden (1 pill vs 2 pills) for treatment-naïve patients. It is recommended by DHHS for treatment-experienced patients who have failed an NNRTI-based regimen and is recommended to be considered by the IAS for patients on older regimens.

*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.

 +DRV/c was found to be bioequivalent to DRV/r in healthy volunteers[2]. 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 for Treatment-Naïve Patients

DHHS: TDF/FTC+DRV/c is "recommended as an initial regimen in certain clinical situations" for treatment-naive patients, because it has durable virologic efficacy, is well-tolerated, has a good toxicity profile, and low pill burden. Clinical situations include when ART is to be started before resistance results are available, such as in acute HIV or other circumstances when rapid ART initiation is needed. In general, boosted DRV is preferred over boosted ATV

 

IAS: TDF/FTC+DRV/c is a recommended initial regimen for individuals in whom an INSTI is not an option.

 

 Recommendations for Treatment-Experienced Patients

DHHS: Recommended in cases of confirmed virologic failure for patients who fail an NNRTI-based regimen (with 2 NRTIs) due to the failure often being a result of NNRTI resistance, rather than NRTI resistance. Patients who are on TDF are recommended to switch to TAF because it offers a better safety profile. In virally suppressed patients, switching to this type of regimen (2 NRTIs + 1 boosted PI) is only recommended for consideration as a within-class regimen to reduce pill burden, improve the safety profile of the drugs or reduce the dosing frequency; for example, switching from a ritonavir-boosted PI to a cobicistat-boosted PI. The DHHS does not recommend a between-class switch to a boosted PI if the drugs in their current regimen are fully active.

IAS: There is no explicit recommendation to switch to this regimen in the IAS guidelines. However, they recommend to consider switching patients on older regimens to regimens with lower pill burden. Other 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

TDF

  • 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

 

DRV/c

  • Must be taken with food
  • High barrier to resistance
  • PI booster (cobicistat) interacts 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 is inferred from studies of DRV/r

 

Efficacy in Clinical Trials

Trial Name

Drugs Compared

Participants

Study Results

N/A

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 [3].

Study 115

DRV/c vs.DRV/r

62

DRV/c is bioequivalent to DRV/r in healthy volunteers [2].

 DRV/r

N/A

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

67, 48% tx-naive

At 48 weeks, 79% achieved viral suppression [4].

ARTEMIS

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 [5].

FLAMINGO

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 [6].

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 [7].

 

 

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