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Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents

Drug Interactions

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

(Last updated: April 8, 2015; last reviewed: April 8, 2015)

Table 20b. Interactions Between Integrase Strand Transfer Inhibitors and Non-Nucleoside Reverse Transcriptase Inhibitors or Protease Inhibitors
ARV Drugs by Drug Class
INSTIs
DTG EVG/c/TDF/FTC EVG
(EVG must be given with a PI/r.)
RAL
NNRTIs
EFV
PK Data
With DTG 50 mg once daily:
  • DTG: AUC ↓ 57%, Cmin ↓ 75%
↑ or ↓ EVG, COBI, EFV possible
↓ EVG expected
RAL
  • AUC ↓ 36%
     

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.
 Do not coadminister. Standard doses
ETR PK Data
ETR 200 mg BID plus DTG 50 mg once daily:
  • DTG AUC ↓ 71% and Cmin ↓ 88%
ETR 200 mg BID with (DRV 600 mg plus RTV 100 mg) BID and DTG 50 mg once daily:
  • DTG AUC ↓ 25% and Cmin ↓ 37%
ETR 200 mg BID with (LPV 400 mg plus RTV 100 mg) BID and DTG 50 mg once daily:
  • DTG AUC ↑ 11% and Cmin ↑ 28%
↑ or ↓ EVG, COBI, ETR possible
No significant interaction between EVG/r and ETR
  • 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.
May coadminister EVG with ETR plus (ATV/r, DRV/r, or LPV/r)

EVG
  • Standard dose depending on the concomitant PI (see below)
Standard doses
NVP
 
PK Data
↓ DTG possible 
↑ or ↓ EVG, COBI, NVP possible
↓ EVG possible
No data
Dose
Do not coadminister.
Do not coadminister.
Do not coadminister.
Standard doses
RPV PK Data
With DTG 50mg once daily:
  • DTG: AUC ↔ and Cmin ↑22%
  • RPV: AUC ↔ and Cmin ↑21%
↑ or ↓ EVG, COBI, RPV possible
↑ RPV expected
  • RPV ↔
  • RAL Cmin ↑ 27% 
Dose
Standard doses
Do not coadminister.
EVG:
  • Standard dose depending on the concomitant PI (see below)
RPV
  • Standard dose
Standard doses
PIs
ATV/c PK Data No data ATV/c plus EVG/c:
  • No data
No data No data
Dose Standard doses  Do not coadminister.  Do not coadminister.
Standard doses
ATV
+/-
RTV
 
PK Data
Unboosted ATV plus DTG 30 mg once daily
  • DTG AUC ↑ 91% and Cmin ↑ 180%
(ATV 300 mg plus RTV 100 mg) once daily plus DTG 30 mg once daily:
  • DTG AUC ↑ 62% and Cmin ↑ 121%
↑ or ↓ EVG, COBI, ATV possible
EVG 85 mg with (ATV 300 mg plus RTV 100 mg) once daily:
  • EVG AUC ↔ and Cmin ↑ 38%
  • ATV AUC and Cmin
With unboosted ATV:
  • RAL AUC ↑ 72%
With (ATV 300 mg plus RTV 100 mg) once daily:
  • RAL AUC ↑ 41%
Dose
Standard doses
Do not coadminister.
  • EVG 85 mg once daily
  • (ATV 300 mg plus RTV 100 mg) once daily
Standard doses
DRV/c PK Data
No data DRV/c plus EVG/c:
  • ↓ EVG possible
No data No data
Dose
Standard doses Do not coadminister. Do not coadminister.
Standard doses
DRV/r
PK Data
(DRV 600 mg plus RTV 100 mg) BID with DTG 30 mg once daily:
  • DTG AUC ↓ 22% and Cmin ↓ 38%
↑ or ↓ EVG, COBI, DRV possible
EVG 125 mg once daily with (DRV 600 mg plus RTV 100 mg) BID:
  • EVG AUC and Cmin
  • DRV AUC and Cmin
With (DRV 600 mg plus RTV 100 mg) BID:
  • RAL AUC ↓ 29% and Cmin ↑ 38%
Dose
Standard doses:
  • Once or twice daily dosing of DRV/r
Do not coadminister.
  • EVG 150 mg once daily
  • (DRV 600 mg plus RTV 100 mg) BID
Standard doses
FPV
+/-
RTV
PK Data
With (FPV 700 mg plus RTV 100 mg) BID and DTG 50 mg once daily:
  • DTG AUC ↓ 35% and Cmin ↓ 49%
↑ or ↓ EVG, COBI, FPV possible
No significant interaction with FPV and EVG FPV: No significant effect
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.
  • EVG 150 mg once daily
  • (FPV 700 mg plus RTV 100 mg) BID
Standard doses
LPV/r
PK Data
With (LPV/r 400 mg plus 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.
EVG 125 mg once daily  with (LPV 400 mg plus RTV 100 mg) BID:
  • EVG AUC ↑ 75% and Cmin ↑ 138%
  • LPV AUC and Cmin
  • ↓ RAL
  • ↔ LPV/r
Dose
Standard doses:
  • Once or twice daily dosing of LPV/r
Do not coadminister.
  • EVG 85 mg once daily
  • (LPV 400 mg plus RTV 100 mg) BID
Standard doses
SQV/r
PK Data
No data ↑ or ↓ EVG, COBI, SQV possible

RTV and COBI have similar effects on CYP3A.
No data No data
Dose
Standard doses
Do not coadminister.
No dosage recommendation Standard doses
TPV/r
PK Data
With (TPV 500 mg plus 
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.
EVG 200 mg once daily with (TPV 500 mg plus RTV 200 mg) BID:
  • EVG AUC and Cmin
  • TPV AUC and Cmin
With (TPV 500 mg plus 
RTV 200 mg) BID
:
  • RAL AUC ↓ 24%
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.
  • EVG 150 mg once daily
  • (TPV 500 mg plus RTV 200 mg) BID
 
Standard doses
a Refer to dolutegravir product labeling for details.

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

Key to Abbreviations: 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, c = cobicistat; CYP = cytochrome P; DRV = darunavir; DRV/c = darunavir/cobicistat; DRV/r = darunavir/ritonavir; DTG = dolutegravir; EFV = efavirenz; ETR = etravirine; EVG = elvitegravir; EVG/c = elvitegravir/cobicistat; EVG/c/TDF/FTC = elvitegravir/cobicistat/tenofovir disoproxil fumarate/emtricitabine; EVG/r = elvitegravir/ritonavir; FPV = fosamprenavir; INSTI = integrase strand transfer inhibitor; LPV = lopinavir; LPV/r = lopinavir/ritonavir; NNRTI = non-nucleoside reverse transcriptase inhibitor; NVP = nevirapine; PI = protease inhibitor; PI/r = ritonavir-boosted protease inhibitor; PK = pharmacokinetic; RAL = raltegravir; RPV = rilpivirine; RTV = ritonavir; SQV = saquinavir; SQV/r = saquinavir/ritonavir; TPV = tipranavir; TPV/r = tipranavir/ritonavir

 

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