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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: May 1, 2014; last reviewed: May 1, 2014)

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Table 19b. Interactions between Integrase Strand Transfer Inhibitors and Non-Nucleoside Reverse Transcriptase Inhibitors or Protease Inhibitors
Drug Class/ARV
INSTI
DTG EVG/cobi/TDF/FTC RAL
NNRTIs
EFV
PK Data
With DTG 50 mg Once Daily:
DTG: AUC ↓ 57%, C
min ↓ 75%
↑ or ↓ EVG, cobi, EFV possible
EFV: AUC ↓ 36%
Dose
DTG 50 mg BID in patients without INSTI resistance 

Consider alternative combination in patients with certain INSTI-associated resistancea or clinically suspected INSTI resistance.
Do not co-administer.
Standard
ETR PK Data
With ETR 200 mg BID plus DTG 50 mg Once Daily:
DTG: AUC ↓ 71%, Cmin ↓ 88%

With ETR 200 mg BID plus DRV/r 600/100 mg BID plus DTG 50 mg Once Daily:
DTG: AUC ↓ 25%, Cmin ↓ 37%

With ETR 200 mg BID plus LPV/r 400 mg/100 mg BID plus DTG 50 mg Once Daily:
DTG: AUC ↑ 11%, Cmin ↑ 28%
↑ or ↓ EVG, cobi, ETR possible
ETR: Cmin ↓ 17%

RAL: C
min ↓ 34%
 
Dose
Do not co-administer ETR and DTG without concurrently administering ATV/r, DRV/r, or LPV/r.

In Patients without INSTI Resistance
DTG 50 mg daily with ETR (concurrently with ATV/r, DRV/r, or LPV/r) 

In Patients with Certain INSTI-Associated Resistance or Clinically Suspected INSTI Resistance:
DTG 50mg BID with ETR (concurrently with ATV/r, DRV/r, or LPV/r)
Do not co-administer.
Standard
NVP
 
PK Data
↓ DTG possible 
↑ or ↓ EVG, cobi, NVP possible
No data
Dose
Do not co-administer.
Do not co-administer.
Standard
RPV PK Data
With DTG 50mg Daily:
DTG: AUC ↔, C
min ↑ 22%
RPV: AUC ↔, Cmin ↑ 21%
↑ or ↓ EVG, cobi, RPV possible
No data
Dose
Standard
Do not co-administer.
No data
PIs
ATV
+/-
RTV
 
PK Data
With Unboosted ATV plus DTG 30 mg Once Daily
DTG: AUC↑ 91%, C
min ↑ 180%

With (ATV 300 mg plus RTV 100 mg) Once Daily plus DTG 30 mg Once Daily:
DTG: AUC ↑ 62%, Cmin ↑ 121%
↑ or ↓ EVG, cobi, ATV possible
With unboosted ATV:
RAL: AUC ↑ 72%

With ATV 300 mg plus RTV 100 mg Once Daily:
RAL: AUC ↑ 41%
Dose
Standard
Do not co-administer.
Standard
DRV
Always use with RTV
PK Data
With (DRV 600 mg plus RTV 100 mg) BID plus DTG 30 mg Once Daily:
DTG: AUC ↓ 22%, C
min ↓ 38%
↑ or ↓ EVG, cobi, DRV possible
With DRV 600 mg plus RTV 100 mg BID:
RAL: AUC ↓ 29% and C
min ↑ 38%
Dose
Standard

Can use either once or twice daily dosing of DRV/r without dose adjustments.
Do not co-administer.
Standard
FPV
+/-
RTV
PK Data
With (FPV 700 mg plus RTV 100 mg) BID plus DTG 50 mg Once Daily:
DTG: AUC ↓ 35%, C
min ↓ 49%
↑ or ↓ EVG, cobi, FPV possible
FPV: No significant effect
Dose
DTG 50 mg BID in patients without INSTI resistance

Consider alternative combination in patients with certain INSTI-associated resistancea or clinically suspected INSTI resistance.
Do not co-administer.
Standard
LPV/r
PK Data
With LPV/r 400 mg/100 mg BID plus 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

Can use either once or twice daily dosing of LPV/r without dose adjustments.
Do not co-administer.
Standard
RTV PK Data
No data with RTV alone
↑ or ↓ EVG, cobi possible

RTV and cobi have similar effects on CYP3A.
With RTV 100 mg BID:
RAL: AUC ↓ 16%
Dose
Refer to other PI/r for dosage recommendation.
Do not co-administer.
Standard
SQV
Always use with RTV
PK Data
No data ↑ or ↓ EVG, cobi, SQV possible

RTV and cobi have similar effects on CYP3A.
No data
Dose
No dosage recommendation
Do not co-administer.
Standard
TPV
Always use with RTV
PK Data
With (TPV 500 mg plus 
RTV 200 mg) BID plus DTG 50 mg Once Daily:

DTG: AUC ↓ 59%, 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:

RAL: AUC ↓ 24%
Dose
DTG: 50 mg BID in patients without INSTI resistance

Consider alternative combination in patients with certain INSTI- associated resistance or clinically suspected INSTI-associated resistance substitutions.
a
Do not co-administer.
Standard
a Refer to Tivicay product label for details.

Key to Acronyms: APV = amprenavir; ART = antiretroviral therapy; ATV = atazanavir; AUC = area under the curve; BID = twice daily; cobi= cobicistat; Cmax = maximum plasma concentration; Cmin = minimum plasma concentration; CYP = cytochrome P; DLV = delavirdine; DRV = darunavir; DRV/r = ritonavir-boosted darunavir; DTG = dolutegravir; EFV = efavirenz; EVG = elvitegravir; ETR = etravirine; FDA = Food and Drug Administration; FPV = fosamprenavir; IDV = indinavir; INSTI = integrase strand transfer inhibitor; LPV = lopinavir; LPV/r = ritonavir-boosted lopinavir; MVC = maraviroc; NFV = nelfinavir; NVP = nevirapine; PI = protease inhibitor; PK = pharmacokinetic; RAL = raltegravir; RPV = rilpivirine; RTV = ritonavir; SQV = saquinavir; SQV/r = ritonavir-boosted saquinavir; TDF = tenofovir disoproxil fumarate; TID = three times a day; TPV = tipranavir

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