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DRV/c*+DTG/RPV is a regimen containing an INSTI and a boosted PI and an NNRTI.  For treatment naïve patients, it is a regimen that might be considered in selective situations when seeking an NRTI-sparing regimen; it is also a regimen that might be considered in selected situations in treatment-experienced patients, particularly with resistance to other drug classes. This regimen has relatively limited data, and its efficacy is extrapolated from other clinical trials of 1PI+1INSTI, or from studies of 1INSTI +1NNRTI.  While some data has suggested that 1PI+1INSTI is inferior to regimens containing 2NRTI+1PI (particularly with high viral load and low CD4), these studies were generally done with RAL as the INSTI.  Whether similar outcomes would have been seen when using DTG, which has higher barrier resistance and potency is unknown, and emerging clinical trial data is promising[1]; similarly, whether similar outcomes would be seen when adding a 3rd active agent (compared to 1INSTI+1PI alone) are unknown. In the TRIO study (ETV+DRV/r+RAL) of patients with multi-drug reistant virus, the combination was found to be well tolerated and had a rate of viral suppression similar to that expectd in a treatment naive paitient; efficacy of DRV/c+DTG/RPV is extrapolated in part from this data. 

*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 in treatment naïve patients

DHHS: This particular regimen is not discussed for treatment-naïve patients. However, a 1 INSTI + 1 PI regimen, DRV/r+RAL, is recommended as an “other” regimen for treatment-naïve patients when an NRTI cannot be used. Based on trial data, the DHHS acknowledges that a regimen of DRV/r+RAL has some potential disadvantages and may be less effective with patients who have high viral loads or low CD4 counts[3].

IAS: DRV/c+DTG/RPV is not discussed in the IAS guidelines. However, a different regimen of 1PI+1INSTI, DRV/r+RAL, is recommended for consideration in situations where patients cannot take ABC, TAF, or TDF because it may be less effective in patients with CD4 cell counts below 200µ/L or HIV RNA levels above 100,000 copies/mL.

Recommendations in treatment-experienced patients

DHHS: In virally suppressed patients, DTG+RPV is now discussed as a 2 drug simplification strategy in patients that are virally suppressed. DHHS guidelines now state that, "DTG plus RPV can be a reasonable option when the use of NRTIs is not desirable and when resistance to either DTG or RPV is not expected."

The DHHS does not currently recommend switching to other PI + INSTI regimens, specifically, ATV/r + RAL, from a 3-drug regimen due to higher rates of virologic failure and discontinuation in patients who switched from ATV/r + TDF/FTC to ATV/r + RAL. However, a recent study showed promising data for switching treatment experienced patients to this particular regimen[1]. Usage of this regimen that includes DTG/RPV (that is recommended), along with an additional PI component are extrapolated from studies of the component regimens. 

In cases of confirmed virologic failure, the DHHS does not explicitly mention this particular regimen, but does recommend considering a regimen of a boosted PI + 1 INSTI after a patient has failed a regimen of an NNRTI with NRTIs. DHHS also recommends considering 1 boosted PI with an INSTI in patients who do not have an INSTI resistance after failing an INSTI + 2 NRTI regimen. Such regimen is also recommended in cases of virologic failure of second-line regimens, as long as the virus is susceptible to INSTIs. This regimen has the potential benefit of additional active drugs when compared to 1PI+1INSTI regimens, but have not been formally studied. 

IAS: IAS does not specifically recommend any regimens for treatment-experienced patients in cases of both virologic failure or suppression. However, IAS does recommend a regimen of 1 PI + 1 INSTI as an alternative regimen for treatment experienced patients.


Other Considerations


  • 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


  • Lowest risk of resistance with virological failure among INSTIs
  • Relatively few drug interactions
  • Can be taken with or without food (but not with polyvalent ions, which may be found in antacids, laxatives, and mineral supplements)
  • May raise serum creatinine 
  • Largest tablet among co-formulated single-pill regimens 
  • Possible side effects include insomnia, headache, and (rarely) hypersensitivity reaction



  • 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


Study Results


DRV/r+DTG (1 arm)

113 tx-experienced

At week 48, the combination of DTG and DRV/r provided a high rate of viral suppression (98.1%), with only one dropout due to drug toxicity [1].

Other Evidence in support of 1 INSTI + 1 PI:






TDF/FTC + LPV/r vs LPV/r + RAL

206 naive

The LPV/r + RAL regimen was found to be noninferior to the regimen of LPV/r + TDF/FTC in both safety and efficacy. Viral suppression at 48 weeks 83% in RAL group vs 85% in TDF/FTC+LPV/r group[4]



94 naive

Similar rates of viral suppression at 24 weeks, but higher incidence of hyperbilirubinemia and RAL resistance development[5]



112 naive

26% virologic failure by 48 weeks, with integrase resistance in 5 participants, particularly in those with baseline viral load>100,000[6]



68 naive

DRV/r+RAL was less effective than DRV/r+TDF/FTC (62.5% of RAL subjects and 83.7% of TDF/FTC subjects were responders (VL<48 copies/mL) at week 48) but better for bone health. However, the proportions of patients achieving VL<200 copies/mL were similar: 72.5% and 86.0%[7]

ANRS143/NEAT 100

DRV/r+RAL vs


805 naive

DRV/r+RAL was noninferior for the primary endpoint of time to treatment failure (17.8%vs 13.8% at 96 weeks); planned subgroup analysis showed RAL arm was inferior for those with CD4<200.[3]


ETR+DRV/r+RAL+Optimized background regimen single arm

103 tx experienced

Phase II study of individuals with multidrug resistant virus who were viremic (HIV vl >1000), had 90% and 86% virologic suppression at 24 and 48 weeks, respectively. [8]


Trial Name

Drugs Compared


Study Results


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 [9].

Study 115

DRV/c vs.DRV/r


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







PI and/or NRTI-based regimens vs RAL + ETR

25 tx-experienced

In a prospective cohort study, virologically suppressed patients on PI or NRTI regimens who expressed concerns due to unwanted side effects were switched to an RAL+ETR regimen. The regimen was wel- tolerated and maintained viral suppression at 48 weeks and the regimen can be considered a well-tolerated potential regimen in certain patients who had difficulty with both PI and NRTI therapy [10].

SWORD 1 and 2

DTG/RPV vs prior combination ART

1024 participants virally suppressed and no history of treatment failure

Virologic suppression was maintained in ~95% of participants in both arms at 48 weeks. 

  • In an observational cohort at eight centers in Italy, 132 subjects were followed for median of 24 months on DTG + RPV.  Most were switched to this regimen for simplification (53%) or toxicity (35%), and nearly half had RT mutations and nearly half had PI mutations, and majority were virally suppressed at time of starting on to DTG +RPV.  At 24 weeks, all but one individual appeared virally suppressed[11]. .
  Open label study of DTG/RPV 38 Heavily experienced with history of treatment failure Three patients discontinued the new regimen due to gastrointestinal toxicity, DDI with omeprazole, and physician’s decision, one case each. There were no virological failures: HIV-RNA remained below 37copies/mL in 100% (38/38) at week 4 and 100% (35/35) at week 48. CD4 count remained stable after switching: median 707.7 cells/mm3 at week 48 (95%CI 591.7-823.6, P=0.99). We observed a statistically improvement in total cholesterol and triglycerides with no changes in HDL and LDL-cholesterol. All total bilirubin, ALT, AST, GGT and alkaline phosphatase decreased (P<0.05). CKD-EPI eGFR decreased from 85 to 76 mL/min/1.73m² (95% CI 5.1-16.6, P=0.0002) at week 4 and maintained stable until week 48.[12].
DORIVIR DTG/RPV 104 participants treatment experienced A total of 104 participants were included, who switched for the following reasons: toxicity/intolerance (42.3%), convenience (27.8%), and drug interactions (17.3%). 82 (78.8%) with virologic suppression and 22 (21.1%) without virologic suppression (8 virologic failure and 14 restarting ART).Prior regimens are protease inhibitor (56.7%), integrase strand transfer inhibitor (26.9%), and non-nucleoside reverse transcriptase inhibitor (16.3%). Efficacy at 24 weeks was 88.4% (intention to treat) and 96.8% (per protocol).  No patient discontinued due to adverse events.[13]

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