Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents Living with HIV

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Drug-Drug Interactions

Interactions between Integrase Inhibitors and Non-Nucleoside Reverse Transcriptase Inhibitors or Protease Inhibitors

Last Updated: October 17, 2017; Last Reviewed: October 17, 2017

Table 19b. Interactions between Integrase Strand Transfer Inhibitors and Non-Nucleoside Reverse Transcriptase Inhibitors or Protease Inhibitors

Recommendations for managing a particular drug interaction may differ depending on whether a new ARV is being initiated in a patient on a stable concomitant medication, or if a new concomitant medication is being initiated in a patient on a stable ARV regimen. The magnitude and significance of drug interactions are difficult to predict when several drugs with competing metabolic pathways are prescribed concomitantly.

Table 19b. Interactions between Integrase Strand Transfer Inhibitors and Non-Nucleoside Reverse Transcriptase Inhibitors or Protease Inhibitors
ARV Drugs by Drug Class
INSTIs
DTG EVG/c RAL
NNRTIs
EFV
PK Data
With DTG 50 mg Once Daily:
  • DTG AUC ↓ 57% and Cmin ↓ 75%
↑ or ↓ EVG, COBI, EFV possible With RAL 400 mg BID:
  • RAL AUC ↓ 36% and Cmin ↓ 21%
With RAL 1200 mg Once Daily:
  • RAL AUC ↓ 14% and Cmin
Dose
In Patients Without INSTI Resistance:
  • DTG 50 mg BID
In Patients With Certain INSTI-Associated Resistancea or Clinically Suspected INSTI Resistance:
  • Consider alternative combination.
Do not coadminister. Standard doses
ETR PK Data ETR 200 mg BID + DTG 50 mg Once Daily:
  • DTG AUC ↓ 71% and Cmin ↓ 88%
ETR 200 mg BID with (DRV 600 mg + RTV 100 mg) BID and DTG 50 mg Once Daily:
  • DTG AUC ↓ 25% and Cmin ↓ 37%
ETR 200 mg BID with (LPV 400 mg + RTV 100 mg) BID and DTG 50 mg Once Daily:
  • DTG AUC ↑ 11% and Cmin ↑ 28%
↑ or ↓ EVG, COBI, ETR possible ETR 200 mg BID + RAL 400 mg BID:
  • ETR Cmin ↑ 17%
  • RAL Cmin ↓ 34%
Dose Do not coadminister ETR and DTG without concurrently administering ATV/r, DRV/r, or LPV/r.

In Patients Without INSTI Resistance:
  • DTG 50 mg once daily with ETR (concurrently with ATV/r, DRV/r, or LPV/r)
In Patients With Certain INSTI-Associated Resistancea or Clinically Suspected INSTI Resistance:
  • DTG 50 mg BID with ETR (concurrently with ATV/r, DRV/r, or LPV/r)
Do not coadminister. RAL 400 mg BID

Coadministration with RAL 1200 mg once daily is not recommended.
NVP PK Data
With DTG 50 mg Once Daily:
  • DTG AUC ↓ 19% and Cmin ↓ 34%
↑ or ↓ EVG, COBI, NVP possible No data
Dose
Standard doses Do not coadminister. Standard doses
RPV PK Data
With DTG 50 mg Once Daily:
  • DTG AUC ↔ and Cmin ↑ 22%
  • RPV AUC ↔ and Cmin ↑ 21%
↑ or ↓ EVG, COBI, RPV possible
  • RPV ↔
  • RAL Cmin ↑ 27%
Dose
Standard doses Do not coadminister. Standard doses
PIs
ATV/c PK Data No data ATV/c + EVG/c:
  • No data
No data
Dose Standard doses Do not coadminister. Standard doses
ATV
+/-
RTV
 
PK Data
Unboosted ATV + DTG 30 mg Once Daily:
  • DTG AUC ↑ 91% and Cmin ↑ 180%
(ATV 300 mg + RTV 100 mg) Once Daily + DTG 30 mg Once Daily:
  • DTG AUC ↑ 62% and Cmin ↑ 121%
↑ or ↓ EVG, COBI, ATV possible With Unboosted ATV:
  • RAL AUC ↑ 72%
With Unboosted ATV and RAL 1200 mg:
  • RAL AUC ↑ 67%
With (ATV 300 mg + RTV 100 mg) Once Daily:
  • RAL AUC ↑ 41%
Dose
Standard doses Do not coadminister. Standard doses
DRV/c PK Data
DTG 50 mg Once Daily and DRV/r Once Daily Switched to DRV/c:
  • DTG Cmin ↑ 100%
DRV/c + EVG/c:
  • ↓ EVG possible
No data
Dose
Standard doses Do not coadminister. Standard doses
DRV/r
PK Data
(DRV 600 mg + RTV 100 mg) BID with DTG 30 mg Once Daily:
  • DTG AUC ↓ 22% and Cmin ↓ 38%
↑ or ↓ EVG, COBI, DRV possible With (DRV 600 mg + RTV 100 mg) BID:
  • RAL AUC ↓ 29% and Cmin ↑ 38%
Dose
Standard doses Do not coadminister. Standard doses
LPV/r PK Data
With (LPV 400 mg + RTV 100 mg) BID and DTG 30 mg Once Daily:
  • DTG: No significant effect
↑ or ↓ EVG, COBI, LPV possible

RTV and COBI have similar effects on CYP3A.
↓ RAL

↔ LPV/r
Dose
Standard doses Do not coadminister. Standard doses
TPV/r
PK Data
With (TPV 500 mg + RTV 200 mg) BID and DTG 50 mg Once Daily:
  • DTG AUC ↓ 59% and Cmin ↓ 76%
↑ or ↓ EVG, COBI, TPV possible

RTV and COBI have similar effects on CYP3A.
With (TPV 500 mg + RTV 200 mg) BID and RAL 400 mg BID:
  • RAL AUC ↓ 24% and Cmin ↓ 55%
Dose
In Patients Without INSTI Resistance:
  • DTG 50 mg BID
In Patients With Certain INSTI-Associated Resistancea or Clinically Suspected INSTI Resistance:
  • Consider alternative combination.
Do not coadminister. RAL 400 mg BID

Coadministration with RAL 1200 mg once daily is not recommended.
a Refer to DTG product labeling for details.

Key to Symbols:
↑ = increase
↓ = decrease
↔ = no change

Key to Acronyms: ARV = antiretroviral; ATV = atazanavir; ATV/c = atazanavir/cobicistat; ATV/r = atazanavir/ritonavir; AUC = area under the curve; BID = twice daily; Cmin = minimum plasma concentration; COBI = cobicistat; CYP = cytochrome P450; DRV = darunavir; DRV/c = darunavir/cobicistat; DRV/r = darunavir/ritonavir; DTG = dolutegravir; EFV = efavirenz; ETR = etravirine; EVG = elvitegravir; EVG/c = elvitegravir/cobicistat; INSTI = integrase strand transfer inhibitor; LPV = lopinavir; LPV/r = lopinavir/ritonavir; NNRTI = non-nucleoside reverse transcriptase inhibitor; NVP = nevirapine; PI = protease inhibitor; PK = pharmacokinetic; RAL = raltegravir; RPV = rilpivirine; RTV = ritonavir; TPV = tipranavir; TPV/r = tipranavir/ritonavir

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