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

Last Updated: October 25, 2018; Last Reviewed: October 25, 2018

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.

^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; BIC = bictegravir; BID = twice daily; Cmin = minimum plasma concentration; COBI = cobicistat; CYP = cytochrome P; DOR = doravirine; 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

ARV Drugs by Drug Class		INSTIs
ARV Drugs by Drug Class		BIC	DTG	EVG/c	RAL
DOR	PK Data	↔ DOR, BIC expected	↔ DOR DTG AUC ↑ 36% and C_min↑ 27%	↑ DOR expected ↔ EVG	↔ DOR, RAL expected
DOR	Dose	Standard doses	Standard doses	Standard doses	Standard doses
EFV	PK Data	↓ BIC expected	With DTG 50 mg Once Daily: DTG AUC ↓ 57% and C_min ↓ 75%	↑ or ↓ EVG, COBI, EFV possible	With RAL 400 mg BID: RAL AUC ↓ 36% and C_min ↓ 21% With RAL 1200 mg Once Daily: RAL AUC ↓ 14% and ↔ C_min
EFV	Dose	Do not coadminister.	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	↓ BIC expected	ETR 200 mg BID plus DTG 50 mg Once Daily: DTG AUC ↓ 71% and C_min ↓ 88% ETR 200 mg BID with (DRV 600 mg plus RTV 100 mg) BID and DTG 50 mg Once Daily: DTG AUC ↓ 25% and C_min ↓ 37% ETR 200 mg BID with (LPV 400 mg plus RTV 100 mg) BID and DTG 50 mg Once Daily: DTG AUC ↑ 11% and C_min ↑ 28%	↑ or ↓ EVG, COBI, ETR possible	ETR 200 mg BID plus RAL 400 mg BID: ETR C_min ↑ 17% RAL C_min ↓ 34%
ETR	Dose	Do not coadminister.	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	↓ BIC expected	With DTG 50 mg Once Daily: DTG AUC ↓ 19% and C_min ↓ 34%	↑ or ↓ EVG, COBI, NVP possible	No data
NVP	Dose	Do not coadminister.	Standard doses	Do not coadminister.	Standard doses
RPV	PK Data	No data	With DTG 50 mg Once Daily: DTG AUC ↔ and C_min ↑ 22% RPV AUC ↔ and C_min ↑ 21%	↑ or ↓ EVG, COBI, RPV possible	↔ RPV RAL C_min↑ 27%
RPV	Dose	Standard doses	Standard doses	Do not coadminister.	Standard doses

ARV Drugs by Drug Class		INSTIs
ARV Drugs by Drug Class		BIC	DTG	EVG/c	RAL
ATV/c	PK Data	BIC AUC ↑ 305%	No data	No data	No data
ATV/c	Dose	Do not coadminister.	Standard doses	Do not coadminister.	Standard doses
ATV +/- RTV	PK Data	BIC AUC ↑ 310%	Unboosted ATV plus DTG 30 mg Once Daily: DTG AUC ↑ 91% and C_min ↑ 180% (ATV 300 mg plus RTV 100 mg) Once Daily plus DTG 30 mg Once Daily: DTG AUC ↑ 62% and C_min ↑ 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 plus RTV 100 mg) Once Daily: RAL AUC ↑ 41%
ATV +/- RTV	Dose	Do not coadminister.	Standard doses	Do not coadminister.	Standard doses
DRV/c	PK Data	BIC AUC ↑ 74%	DRV/c plus DTG Once Daily: ↔ DTG, DRV, COBI DTG 50 mg Once Daily and DRV/r Once Daily Switched to DRV/c: DTG C_min ↑ 100%	DRV/c plus EVG/c: ↓ EVG possible	No data
DRV/c	Dose	Standard doses	Standard doses	Do not coadminister.	Standard doses
DRV/r	PK Data	No data	(DRV 600 mg plus RTV 100 mg) BID with DTG 30 mg Once Daily: DTG AUC ↓ 22% and C_min ↓ 38%	↑ or ↓ EVG, COBI, DRV possible	With (DRV 600 mg plus RTV 100 mg) BID: RAL AUC ↓ 29% and C_min ↑ 38%
DRV/r	Dose	Standard doses	Standard doses	Do not coadminister.	Standard doses
LPV/r	PK Data	No data	With (LPV 400 mg plus RTV 100 mg) BID and DTG 30 mg Once Daily: ↔ DTG	↑ or ↓ EVG, COBI, LPV possible RTV and COBI have similar effects on CYP3A.	↓ RAL ↔ LPV/r
LPV/r	Dose	Consider alternative combination.	Standard doses	Do not coadminister.	Standard doses
TPV/r	PK Data	↓ BIC possible	With (TPV 500 mg plus RTV 200 mg) BID and DTG 50 mg Once Daily: DTG AUC ↓ 59% and C_min ↓ 76%	↑ or ↓ EVG, COBI, TPV possible RTV and COBI have similar effects on CYP3A.	With (TPV 500 mg plus RTV 200 mg) BID and RAL 400 mg BID: RAL AUC ↓ 24% and C_min ↓ 55%
TPV/r	Dose	Do not coadminister.	In Patients Without INSTI Resistance: DTG 50 mg BID In Patients With Certain INSTI-Associated Resistance^a 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.