Updated
Reviewed
Jun. 03, 2021

Drug-Drug Interactions

Interactions between Non-Nucleoside Reverse Transcriptase Inhibitors and Protease Inhibitors

Table 25a. Interactions Between Non-Nucleoside Reverse Transcriptase Inhibitors and Protease Inhibitors

Note: Interactions associated with DLV, FPV, IDV, NFV, TPV, and SQV are not included in this table. Please refer to the Food and Drug Administration product labels for information regarding interactions between these drugs and other concomitant drugs.

Rilpivirine (RPV) intramuscular (IM) is not included in this table, because the combination of cabotegravir IM plus RPV IM is a two-drug co-packaged product. Therefore, RPV IM is not expected to be used as a protease inhibitor.

Table 25a. Interactions Between Non-Nucleoside Reverse Transcriptase Inhibitors and Protease Inhibitors
PIs NNRTIs
DOR EFV ETR NVP RPV
ATV
Unboosted
PK Data ↑ DOR expected

↔ ATV expected
↔ EFV

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

↔ ATV AUC and Cmin ↓ 47%
↑ NVP possible

↓ ATV possible
↑ RPV PO possible

↔ ATV expected
Dose No dose adjustment needed. Do not coadminister. Do not coadminister. Do not coadminister. No dose adjustment needed.
ATV/c PK Data ↑ DOR expected

↔ ATV expected
↔ EFV expected

↓ ATV possible

↓ COBI possible
↑ ETR possible

↓ ATV possible

↓ COBI possible
↑ NVP possible

↓ ATV possible

↓ COBI possible
↑ RPV PO possible

↔ ATV expected
Dose No dose adjustment needed. ATV/c in ART-Naive Patients:
  • ATV 400 mg plus COBI 150 mg once daily
  • Do not use coformulated ATV 300 mg/COBI 150 mg.
ATV/c in ART-Experienced Patients:
  • Do not coadminister.
No dose adjustment needed for EFV.
Do not coadminister. Do not coadminister. No dose adjustment needed.
ATV/r PK Data ↑ DOR expected

↔ ATV expected
↔ EFV expected

(ATV 400 mg plus RTV 100 mg) Once Daily:
  • ATV concentrations similar to (ATV 300 mg plus RTV 100 mg) without EFV
(ATV 300 mg plus RTV 100 mg) Once Daily:
  • ETR AUC and Cmin both ↑ ~30%
  • ↔ ATV AUC and Cmin
(ATV 300 mg plus RTV 100 mg) Once Daily:
  • ATV AUC ↓ 42% and Cmin ↓ 72%
  • NVP AUC ↑ 25%
↑ RPV PO possible

↔ ATV expected
Dose No dose adjustment needed. ATV/r in ART-Naive Patients:
  • (ATV 400 mg plus RTV 100 mg) once daily
ATV/r in ART-Experienced Patients:
  • Do not coadminister.
No dose adjustment needed for EFV.
No dose adjustment needed. Do not coadminister. No dose adjustment needed.
DRV/c PK Data ↑ DOR expected

↔ DRV expected
↔ EFV expected

↓ DRV possible

↓ COBI possible
ETR 400 mg Once Daily with (DRV 800 mg plus COBI 150 mg) Once Daily:
  • ↔ ETR AUC and Cmin
  • ↔ DRV AUC and Cmin ↓ 56%
  • COBI AUC ↓ 30% and Cmin ↓ 66%
↑ NVP possible

↓ DRV possible

↓ COBI possible
↔ DRV expected

↑ RPV PO possible
Dose No dose adjustment needed. Do not coadminister. Do not coadminister. Do not coadminister. No dose adjustment needed.
DRV/r PK Data ↑ DOR expected

↔ DRV expected
With (DRV 300 mg plus RTV 100 mg) Twice Daily:
  • EFV AUC ↑ 21%
  • ↔ DRV AUC and Cmin ↓ 31%
ETR 100 mg Twice Daily with (DRV 600 mg plus RTV 100 mg) Twice Daily:
  • ETR AUC ↓ 37% and Cmin ↓ 49%
  • ↔ DRV
With (DRV 400 mg plus RTV 100 mg) Twice Daily:
  • NVP AUC ↑ 27% and Cmin ↑ 47%
  • DRV AUC ↑ 24%a
RPV 150 mg PO Once Daily with (DRV 800 mg plus RTV 100 mg) Once Daily:
  • RPV PO AUC ↑ 130% and Cmin ↑ 178%
  • ↔ DRV
Dose No dose adjustment needed. Clinical significance unknown. Use standard doses and monitor patient closely. Consider monitoring drug levels. No dose adjustment needed.

Despite reduced ETR concentration, safety and efficacy of this combination have been established in a clinical trial.
No dose adjustment needed. No dose adjustment needed.
LPV/r PK Data ↑ DOR expected

↔ LPV expected
↔ EFV expected

With LPV/r 500 mg/125 mgTwice Daily:
  • LPV concentration similar to that of LPV/r 400 mg/100 mg twice daily without EFV
ETR AUC ↓ 35% (comparable to the decrease seen with DRV/r)

↔ LPV AUC
↑ NVP possible

LPV AUC ↓ 27% and Cmin ↓ 51%
RPV 150 mg PO Once Daily with LPV/r:
  • RPV PO AUC ↑ 52% and Cmin ↑ 74%
  • ↔ LPV
Dose No dose adjustment needed. LPV/r 500 mg/125 mga twice daily

LPV/r 533 mg/133 mg twice daily when using oral solution

No dose adjustment needed for EFV.
No dose adjustment needed. LPV/r 500 mg/125 mga twice daily

LPV/r 533 mg/133 mg twice daily when using oral solution

No dose adjustment needed for NVP.
No dose adjustment needed.
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: ART = antiretroviral therapy; ATV = atazanavir; ATV/c = atazanavir/cobicistat; ATV/r = atazanavir/ritonavir; AUC = area under the curve; Cmin = minimum plasma concentration; COBI = cobicistat; DLV = delavirdine; DOR = doravirine; DRV = darunavir; DRV/c = darunavir/cobicistat; DRV/r = darunavir/ritonavir; EFV = efavirenz; ETR = etravirine; FPV = fosamprenavir; IDV = indinavir; IM = intramuscular; LPV = lopinavir; LPV/r = lopinavir/ritonavir; NFV = nelfinavir; NNRTI = non-nucleoside reverse transcriptase inhibitor; NVP = nevirapine; PI = protease inhibitor; PO = oral; PK = pharmacokinetic; RPV = rilpivirine; RTV = ritonavir; SQV = saquinavir; TPV = tipranavir.

Drug-Drug Interactions

Interactions between Non-Nucleoside Reverse Transcriptase Inhibitors and Protease Inhibitors

Table 25a. Interactions Between Non-Nucleoside Reverse Transcriptase Inhibitors and Protease Inhibitors

Note: Interactions associated with DLV, FPV, IDV, NFV, TPV, and SQV are not included in this table. Please refer to the Food and Drug Administration product labels for information regarding interactions between these drugs and other concomitant drugs.

Rilpivirine (RPV) intramuscular (IM) is not included in this table, because the combination of cabotegravir IM plus RPV IM is a two-drug co-packaged product. Therefore, RPV IM is not expected to be used as a protease inhibitor.

Table 25a. Interactions Between Non-Nucleoside Reverse Transcriptase Inhibitors and Protease Inhibitors
PIs NNRTIs
DOR EFV ETR NVP RPV
ATV
Unboosted
PK Data ↑ DOR expected

↔ ATV expected
↔ EFV

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

↔ ATV AUC and Cmin ↓ 47%
↑ NVP possible

↓ ATV possible
↑ RPV PO possible

↔ ATV expected
Dose No dose adjustment needed. Do not coadminister. Do not coadminister. Do not coadminister. No dose adjustment needed.
ATV/c PK Data ↑ DOR expected

↔ ATV expected
↔ EFV expected

↓ ATV possible

↓ COBI possible
↑ ETR possible

↓ ATV possible

↓ COBI possible
↑ NVP possible

↓ ATV possible

↓ COBI possible
↑ RPV PO possible

↔ ATV expected
Dose No dose adjustment needed. ATV/c in ART-Naive Patients:
  • ATV 400 mg plus COBI 150 mg once daily
  • Do not use coformulated ATV 300 mg/COBI 150 mg.
ATV/c in ART-Experienced Patients:
  • Do not coadminister.
No dose adjustment needed for EFV.
Do not coadminister. Do not coadminister. No dose adjustment needed.
ATV/r PK Data ↑ DOR expected

↔ ATV expected
↔ EFV expected

(ATV 400 mg plus RTV 100 mg) Once Daily:
  • ATV concentrations similar to (ATV 300 mg plus RTV 100 mg) without EFV
(ATV 300 mg plus RTV 100 mg) Once Daily:
  • ETR AUC and Cmin both ↑ ~30%
  • ↔ ATV AUC and Cmin
(ATV 300 mg plus RTV 100 mg) Once Daily:
  • ATV AUC ↓ 42% and Cmin ↓ 72%
  • NVP AUC ↑ 25%
↑ RPV PO possible

↔ ATV expected
Dose No dose adjustment needed. ATV/r in ART-Naive Patients:
  • (ATV 400 mg plus RTV 100 mg) once daily
ATV/r in ART-Experienced Patients:
  • Do not coadminister.
No dose adjustment needed for EFV.
No dose adjustment needed. Do not coadminister. No dose adjustment needed.
DRV/c PK Data ↑ DOR expected

↔ DRV expected
↔ EFV expected

↓ DRV possible

↓ COBI possible
ETR 400 mg Once Daily with (DRV 800 mg plus COBI 150 mg) Once Daily:
  • ↔ ETR AUC and Cmin
  • ↔ DRV AUC and Cmin ↓ 56%
  • COBI AUC ↓ 30% and Cmin ↓ 66%
↑ NVP possible

↓ DRV possible

↓ COBI possible
↔ DRV expected

↑ RPV PO possible
Dose No dose adjustment needed. Do not coadminister. Do not coadminister. Do not coadminister. No dose adjustment needed.
DRV/r PK Data ↑ DOR expected

↔ DRV expected
With (DRV 300 mg plus RTV 100 mg) Twice Daily:
  • EFV AUC ↑ 21%
  • ↔ DRV AUC and Cmin ↓ 31%
ETR 100 mg Twice Daily with (DRV 600 mg plus RTV 100 mg) Twice Daily:
  • ETR AUC ↓ 37% and Cmin ↓ 49%
  • ↔ DRV
With (DRV 400 mg plus RTV 100 mg) Twice Daily:
  • NVP AUC ↑ 27% and Cmin ↑ 47%
  • DRV AUC ↑ 24%a
RPV 150 mg PO Once Daily with (DRV 800 mg plus RTV 100 mg) Once Daily:
  • RPV PO AUC ↑ 130% and Cmin ↑ 178%
  • ↔ DRV
Dose No dose adjustment needed. Clinical significance unknown. Use standard doses and monitor patient closely. Consider monitoring drug levels. No dose adjustment needed.

Despite reduced ETR concentration, safety and efficacy of this combination have been established in a clinical trial.
No dose adjustment needed. No dose adjustment needed.
LPV/r PK Data ↑ DOR expected

↔ LPV expected
↔ EFV expected

With LPV/r 500 mg/125 mgTwice Daily:
  • LPV concentration similar to that of LPV/r 400 mg/100 mg twice daily without EFV
ETR AUC ↓ 35% (comparable to the decrease seen with DRV/r)

↔ LPV AUC
↑ NVP possible

LPV AUC ↓ 27% and Cmin ↓ 51%
RPV 150 mg PO Once Daily with LPV/r:
  • RPV PO AUC ↑ 52% and Cmin ↑ 74%
  • ↔ LPV
Dose No dose adjustment needed. LPV/r 500 mg/125 mga twice daily

LPV/r 533 mg/133 mg twice daily when using oral solution

No dose adjustment needed for EFV.
No dose adjustment needed. LPV/r 500 mg/125 mga twice daily

LPV/r 533 mg/133 mg twice daily when using oral solution

No dose adjustment needed for NVP.
No dose adjustment needed.
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: ART = antiretroviral therapy; ATV = atazanavir; ATV/c = atazanavir/cobicistat; ATV/r = atazanavir/ritonavir; AUC = area under the curve; Cmin = minimum plasma concentration; COBI = cobicistat; DLV = delavirdine; DOR = doravirine; DRV = darunavir; DRV/c = darunavir/cobicistat; DRV/r = darunavir/ritonavir; EFV = efavirenz; ETR = etravirine; FPV = fosamprenavir; IDV = indinavir; IM = intramuscular; LPV = lopinavir; LPV/r = lopinavir/ritonavir; NFV = nelfinavir; NNRTI = non-nucleoside reverse transcriptase inhibitor; NVP = nevirapine; PI = protease inhibitor; PO = oral; PK = pharmacokinetic; RPV = rilpivirine; RTV = ritonavir; SQV = saquinavir; TPV = tipranavir.

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