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

Drug Interactions

Interactions between Non-Nucleoside Reverse Transcriptase Inhibitors and Protease Inhibitors

(Last updated:3/27/2012; last reviewed:5/1/2014)

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Table 19a. Interactions between Non-Nucleoside Reverse Transcriptase Inhibitors, and Protease Inhibitorsa 

a DLV, IDV, and NFV are not included in this table. Refer to the DLV, IDV, and NFV Food and Drug Administration package inserts for information regarding drug interactions.

 
Table 19a. Interactions between Non-Nucleoside Reverse Transcriptase Inhibitors, and Protease Inhibitors*
 
PIs
 NNRTIs
EFV ETR NVP RPVa
ATV
 +/-
RTV
PK data With Unboosted ATV:
ATV: AUC ↓ 74%
EFV: no significant change

With ATV 300 mg plus RTV 100 mg Once Daily with Food:
ATV concentrations similar to those with unboosted ATV without EFV
 
With Unboosted ATV:
ETR: AUC ↑ 50%, Cmin ↑ 58%
ATV: AUC ↓ 17%, Cmin ↓ 47%

With ATV 300 mg plus RTV 100 mg Once Daily:
ETR: AUC and Cmin ↑ approximately 30%
ATV: AUC ↓ 14%, Cmin ↓ 38% 
 
With ATV 300 mg plus RTV 100 mg Once Daily:
ATV: AUC ↓ 42%, Cmin ↓ 72%
NVP: AUC ↑ 25% 
 
With Boosted and Unboosted ATV:
↑ RPV possible
 
Dose Do not co-administer with unboosted ATV.

In ART-Naive Patients:
(ATV 400 mg plus RTV 100 mg) once daily

Do not co-administer in ART experienced patients.
 
Do not co-administer with ATV +/− RTV. Do not co-administer with ATV +/− RTV. Standard
DRV

Always use with RTV
PK Data With DRV 300 mg plus RTV 100 mg BID:
DRV: AUC ↓ 13%, Cmin ↓ 31%
EFV: AUC ↑ 21%
 
ETR 100 mg BID with DRV 600 mg plus RTV 100 mg BID:
DRV: no significant change
ETR: AUC ↓ 37%, Cmin ↓ 49%
 
With DRV 400 mg plus RTV 100 mg BID:
DRV: AUC ↑ 24%b
NVP: AUC ↑ 27%, Cmin ↑ 47%
 
RPV 150 mg Once Daily with DRV 800 mg plus RTV 100 mg Once Daily:
DRV: no significant change
RPV: AUC ↑ 130%, Cmin ↑ 178%
 
Dose Clinical significance unknown. Use standard doses and monitor patient closely. Consider monitoring drug levels. Standard (ETR 200 mg BID)

Safety and efficacy of this combination, despite decreased ETR concentration, have been established in a clinical trial.
 
Standard Standard
FPV PK Data With FPV 1400 mg plus RTV 200 mg Once Daily:
APV: Cmin ↓ 36%
 
With FPV 700 mg plus RTV 100 mg BID:
APV: AUC ↑ 69%, Cmin ↑ 77%
 
With Unboosted FPV 1400 mg BID:
APV: AUC ↓ 33%
NVP: AUC ↑ 29%

With FPV 700 mg plus RTV 100 mg BID:
NVP: Cmin ↑ 22%  
 
With Boosted and Unboosted FPV:
↑ RPV possible
 
Dose FPV 1400 mg plus RTV 300 mg once daily or FPV 700 mg plus RTV 100 mg BID

EFV standard
 
Do not co-administer with FPV +/− RTV. FPV 700 mg plus RTV 100 mg BID

NVP standard
 
Standard
LPV/r PK Data With LPV/r Tablets 500/125 mg BIDc plus EFV 600 mg:
LPV levels similar to LPV/r 400/100 mg BID without EFV
 
With LPV/r Tablets:
ETR: AUC ↓ 35% (comparable to the decrease with DRV/r)
LPV: AUC↓ 13%
 
With LPV/r Capsules:
LPV: AUC ↓ 27%, Cmin ↓51% 
 
RPV 150 mg Once Daily with LPV/r Capsules:
LPV: no significant change
RPV: AUC ↑ 52%, Cmin ↑ 74%
 
Dose LPV/r tablets 500/125 mgc BID; LPV/r oral solution 533/133 mg BID

EFV standard
 
Standard LPV/r tablets 500/125 mgc BID; LPV/r oral solution 533/133 mg BID

NVP standard
Standard
RTV PK Data Refer to information for boosted PI. Refer to information for boosted PI. Refer to information for boosted PI. Refer to information for boosted PI.
Dose
SQV

Always use with RTV
PK Data With SQV 1200 mg TID:
SQV: AUC ↓ 62%
EFV: AUC ↓ 12%
 
With SQV 1000 mg plus RTV 100 mg BID:
SQV: AUC unchanged 
ETR: AUC ↓ 33%, Cmin ↓ 29%

Reduced ETR levels similar to reduction with DRV/r
With 600 mg TID:
SQV: AUC ↓ 24%
NVP: no significant change
 
↑ RPV possible
Dose (SQV 1000 mg plus RTV 100 mg) BID SQV 1000 mg plus 
RTV 100 mg BID
Dose with SQV/r not established Standard
TPV
(always use with RTV)
PK Data With TPV 500 mg plus 
RTV 100 mg BID: 

TPV: AUC ↓ 31%, Cmin ↓ 42%
EFV: no significant change

With TPV 750 mg plus 
RTV 200 mg BID:

TPV: no significant change
EFV: no significant change
With TPV 500 mg plus 
RTV 200 mg BID
:
ETR: AUC ↓ 76%, Cmin ↓ 82%
TPV: AUC ↑ 18%, Cmin ↑ 24%
 
With (TPV 250 mg plus 
RTV 200 mg) BID and with (TPV 750 mg plus 
RTV 100 mg) BID
:
NVP: no significant change
TPV: no data
 
↑ RPV possible
Dose Standard Do not co-administer.  Standard Standard
a Approved dose for RPV is 25 mg once daily. Most PK interaction studies were performed using 75 mg to 150 mg RPV per dose.
b Based on between-study comparison.
c Use a combination of two LPV/r 200 mg/50 mg tablets plus one LPV/r 100 mg/25 mg tablet to make a total dose of LPV/r 500 mg/125 mg.

Key to Acronyms: APV = amprenavir; ART = antiretroviral therapy; ATV = atazanavir; AUC = area under the curve; BID = twice daily; Cmax = maximum plasma concentration; Cmin = minimum plasma concentration; CYP = cytochrome P; DLV = delavirdine; DRV = darunavir; DRV/r = ritonavir-boosted darunavir; EFV = efavirenz; ETR = etravirine; FDA = Food and Drug Administration; FPV = fosamprenavir; IDV = indinavir; LPV = lopinavir; LPV/r = ritonavir-boosted lopinavir; MVC = maraviroc; NFV = nelfinavir; NVP = nevirapine; PI = protease inhibitor; PK = pharmacokinetic; 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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