Antiretroviral Guidelines

US DHHS Guidelines with Australian commentary

Interactions between Non-Nucleoside Reverse Transcriptase Inhibitors and Protease Inhibitors

Last Updated: October 25, 2018; Last Reviewed: October 25, 2018

Note: Delavirdine (DLV), fosamprenavir (FPV), indinavir (IDV), nelfinavir (NFV), and saquinavir (SQV) are not included in this table. Please refer to the Food and Drug Administration product labels for DLV, FPV, IDV, NFV, and SQV for information regarding drug interactions.

AU comment: Pharmacokinetic enhancers - COBI

PIs NNRTIs
DOR EFV ETR NVP RPVa
ATV
Unboosted		 PK Data ↑ DOR expected

↔ ATV expected		 ↔ EFV 

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

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

↔ ATV expected		 ↓ ATV possible 

↓ COBI possible		 ↓ ATV possible 

↓ COBI possible		 ↓ ATV possible 

↓ COBI possible		 ↑ RPV possible 

↔ ATV expected
Dose Standard doses EFV standard dose 

In ART-Naive Patients:
  • ATV 400 mg plus COBI 150 mg once daily
  • Do not use coformulated ATV/c 300 mg/150 mg.
In ART-Experienced Patients:
  • Do not coadminister.
 Do not coadminister. Do not coadminister. Standard doses
ATV/r PK Data ↑ DOR expected

↔ ATV 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 possible
Dose Standard doses EFV standard dose

In ART-Naive Patients:
  • (ATV 400 mg plus RTV 100 mg) once daily
In ART-Experienced Patients:
  • Do not coadminister.
 ETR standard dose 

(ATV 300 mg plus RTV 100 mg) once daily		 Do not coadminister. Standard doses
DRV/c PK Data ↑ DOR expected

↔ DRV 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%
 ↓ DRV possible 

↓ COBI possible		 ↔ DRV expected 

↑ RPV possible
Dose Standard doses Do not coadminister. Do not coadminister. Do not coadminister. Standard doses
DRV/r PK Data ↑ DOR expected

↔ DRV expected		 With (DRV 300 mg plus RTV 100 mg) BID:
  • EFV AUC ↑ 21%
  • ↔ DRV AUC and Cmin ↓ 31%
 ETR 100 mg BID with (DRV 600 mg plus RTV 100 mg) BID:
  • ETR AUC ↓ 37% and Cmin ↓ 49%
  • ↔ DRV
 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
Dose Standard doses Clinical significance unknown. Use standard doses and monitor patient closely. Consider monitoring drug levels. Standard doses 

Despite reduced ETR concentration, safety and efficacy of this combination have been established in a clinical trial.		 Standard doses Standard doses
LPV/r PK Data ↑ DOR expected

↔ LPV expected		 With LPV/r Tablets 500 mg/125 mgc BID:
  • LPV concentration similar to that of LPV/r 400 mg/100 mg BID without EFV
 With LPV/r Tablets:
  • ETR AUC ↓ 35% (comparable to the decrease with DRV/r)
  • ↔ LPV AUC
 With LPV/r Capsules:
  • LPV AUC ↓ 27% and Cmin ↓ 51%
 RPV 150 mg Once Daily with LPV/r Capsules:
  • LRPV AUC ↑ 52% and Cmin ↑ 74%
  • ↔ LPV
Dose Standard doses LPV/r tablets 500 mg/125 mgc BID; LPV/r oral solution 533 mg/133 mg BID 

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

NVP standard dose		 Standard doses
TPV/r

Always use TPV with RTV		 PK Data ↑ DOR expected

↔ TPV expected		 With (TPV 500 mg plus RTV 100 mg) BID:
  • ↔ EFV
  • TPV AUC ↓ 31% and Cmin ↓ 42%
With (TPV 750 mg plus RTV 200 mg) BID:
  • ↔ EFV and TPV
 With (TPV 500 mg plus RTV 200 mg) BID:
  • ETR AUC ↓ 76% and Cmin ↓ 82%
  • ↔ TPV AUC and Cmin ↑ 24%
 With (TPV 250 mg plus RTV 200 mg) BID or with (TPV 750 mg plus RTV 100 mg) BID:
  • ↔ NVP
  • ↔ TPV expected
 ↑ RPV possible
Dose Standard doses 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 RPV 75 mg to 150 mg per dose.
b DRV concentration was compared to a historic control.
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: ART = antiretroviral therapy; ATV = atazanavir; ATV/c = atazanavir/cobicistat; ATV/r = atazanavir/ritonavir; AUC = area under the curve; BID = twice daily; Cmin = minimum plasma concentration; COBI = cobicistat; DOR = doravirine; DRV = darunavir; DRV/c = darunavir/cobicistat; DRV/r = darunavir/ritonavir; EFV = efavirenz; ETR = etravirine; LPV = lopinavir; LPV/r = lopinavir/ritonavir; NNRTI = non-nucleoside reverse transcriptase inhibitor; NVP = nevirapine; PI = protease inhibitor; PK = pharmacokinetic; RPV = rilpivirine; RTV = ritonavir; TPV = tipranavir