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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: April 8, 2015; last reviewed: April 8, 2015)

Table 20a. Interactions between Non-Nucleoside Reverse Transcriptase Inhibitors and Protease Inhibitorsa

Note: 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 20a. Interactions Between Non-Nucleoside Reverse Transcriptase Inhibitors and Protease Inhibitorsa
PIs NNRTIs
  EFV ETR NVP RPVa
 ATV Unboosted
PK Data EFV: no significant change

ATV AUC ↓ 74%
ETR AUC ↑ 50% and Cmin ↑ 58%

ATV AUC ↓ 17% and Cmin ↓ 47%
↓ ATV possible ↑ RPV possible
Dose Do not coadminister. Do not coadminister. Do not coadminister. Standard doses
ATV/c PK Data
↓ ATV

↓ COBI
↓ ATV

↓ COBI
↓ COBI ↑ RPV possible

↔ ATV expected
Dose
EFV standard dose

In ART-Naive Patients:
  • ATV 400 mg plus COBI 150 mg Once Daily
Do not coadminister in ART-experienced patients.
Do not coadminister. Do not coadminister. Standard doses
 ATV/r PK Data (ATV 300 mg plus RTV 100 mg) Once Daily:
  • ATV concentrations are similar to those with unboosted ATV without EFV.

(ATV 300 mg plus RTV 100 mg) Once Daily:

  • ETR AUC and Cmin both ↑ ~30%
  • ATV AUC ↔ and Cmin ↓ 18%

(ATV 300 mg plus RTV 100 mg) Once Daily:

  • ATV AUC ↓ 42% and Cmin ↓ 72%
  • NVP AUC ↑ 25%
↑ RPV possible
Dose EFV standard dose

In ART-Naive Patients:
  • (ATV 400 mg plus RTV 100 mg) Once Daily
Do not coadminister in ART-experienced patients.
ETR standard dose

(ATV 300 mg plus RTV 100 mg) Once Daily
Do not coadminister. Standard doses
DRV/c PK Data ↓ DRV possible

↓ COBI possible
Effect on DRV unknown

↓ COBI possible
Effect on DRV unknown

↓ COBI possible
↔ DRV expected

↑ RPV possible
Dose Do not coadminister. Do not coadminister. Do not coadminister. Standard doses
DRV/r PK Data With (DRV 300 mg plus RTV 100 mg) BID:
  • EFV AUC ↑ 21%
  • DRV AUC ↓ 13% and Cmin ↓ 31%
ETR 100 mg BID with (DRV 600 mg plus RTV 100 mg) BID:
  • ETR AUC ↓ 37% and Cmin ↓ 49%
  • DRV: no significant change
With (DRV 400 mg plus RTV 100 mg) BID:
  • NVP AUC ↑ 27% and Cmin ↑ 47%
  • DRV AUC ↑ 24%b
RPV 150 mg Once Daily with (DRV 800 mg plus RTV 100 mg) Once Daily:
  • RPV AUC ↑ 130% and Cmin ↑ 178%
  • DRV: no significant change
Dose Clinical significance unknown. Use standard doses and monitor patient closely. Consider monitoring drug levels. Standard doses

Safety and efficacy of this combination, despite reduced ETR concentration, have been established in a clinical trial.
Standard doses Standard doses
FPV +/- RTV 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% and Cmin ↑ 77%
With Unboosted FPV 1400 mg BID:
  • NVP AUC ↑ 29%
  • APV AUC ↓ 33%
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 dose Do not coadminister with FPV +/− RTV. (FPV 700 mg plus RTV 100 mg) BID

NVP standard dose
Standard doses
LPV/r PK Data With LPV/r Tablets 500/125 mgc BID:
  • LPV concentration similar to that with 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% and Cmin ↓ 51%
RPV 150 mg Once Daily with LPV/r Capsules:
  • RPV AUC ↑ 52% and Cmin ↑ 74%
  • LPV no significant change
Dose

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

EFV standard dose

Standard doses

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

NVP standard dose

Standard doses
SQV
Always use with RTV
PK Data With SQV 1200 mg TID:
  • EFV AUC ↓ 12%
  • SQV AUC ↓ 62%
With (SQV 1000 mg plus RTV 100 mg) BID:
  • ETR AUC ↓ 33% and Cmin ↓ 29%
  • SQV AUC ↔
↓ ETR levels similar to reduction with DRV/r
With SQV 600 mg TID:
  • NVP: no significant change
  • SQV AUC ↓ 24%
↑ 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 doses
TPV
Always use with RTV
PK Data With (TPV 500 mg plus RTV 100 mg) BID:
  • EFV no significant change
  • TPV AUC ↓ 31% and Cmin ↓ 42%
With (TPV 750 mg plus RTV 200 mg) BID:
  • EFV: no significant change
  • TPV: no significant change
With (TPV 500 mg plus RTV 200 mg) BID:
  • ETR AUC ↓ 76% and Cmin ↓ 82%
  • TPV AUC ↑ 18% and Cmin ↑ 24%
With (TPV 250 mg plus RTV 200 mg) BID or with (TPV 750 mg plus RTV 100 mg) BID:
  • NVP: no significant change
  • TPV: no data
↑ RPV possible
Dose Standard doses Do not coadminister. Standard doses Standard doses

a Approved dose for RPV is 25 mg once daily. Most PK 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 Symbols: ↑ = increase, ↓ = decrease, ↔ = no change

Key to Acronyms: APV = amprenavir; ART = antiretroviral therapy; ATV = atazanavir; ATV/c = atazanavir/cobicistat; AUC = area under the curve; BID = twice daily; Cmax = maximum plasma concentration; Cmin = minimum plasma concentration; CYP = cytochrome P; DLV = delavirdine; DRV = darunavir; DRV/c = darunavir/cobicistat; DRV/r = darunavir/ritonavir; EFV = efavirenz; ETR = etravirine; FDA = Food and Drug Administration; FPV = fosamprenavir; IDV = indinavir; LPV = lopinavir; LPV/r = lopinavir/ritonavir; NFV = nelfinavir; NVP = nevirapine; PK = pharmacokinetic; RPV = rilpivirine; RTV = ritonavir; SQV = saquinavir; SQV/r = saquinavir/ritonavir; TID = three times a day; TPV = tipranavir

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