Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents Living with HIV

The information in the brief version is excerpted directly from the full-text guidelines. The brief version is a compilation of the tables and boxed recommendations.

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Drug-Drug Interactions

Interactions between Integrase Inhibitors and Non-Nucleoside Reverse Transcriptase Inhibitors or Protease Inhibitors

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

Table 20b. Interactions between Integrase Strand Transfer Inhibitors and Non-Nucleoside Reverse Transcriptase Inhibitors or Protease Inhibitors

Recommendations for managing a particular drug interaction may differ depending on whether a new ARV is being initiated in a patient on a stable concomitant medication, or if a new concomitant medication is being initiated in a patient on a stable ARV regimen. The magnitude and significance of drug interactions are difficult to predict when several drugs with competing metabolic pathways are prescribed concomitantly.

Table 20b. Interactions between Integrase Strand Transfer Inhibitors and Non-Nucleoside Reverse Transcriptase Inhibitors or Protease Inhibitors
ARV Drugs by Drug Class
INSTIs
BIC DTG EVG/c RAL
NNRTIs
DOR
PK Data
↔ DOR, BIC expected ↔ DOR

DTG AUC ↑ 36% and Cmin ↑ 27%
↑ DOR expected

↔ EVG
↔ DOR, RAL expected
Dose
Standard doses Standard doses Standard doses Standard doses
EFV
PK Data
↓ BIC expected With DTG 50 mg Once Daily:
  • DTG AUC ↓ 57% and Cmin ↓ 75%
↑ or ↓ EVG, COBI, EFV possible With RAL 400 mg BID:
  • RAL AUC ↓ 36% and Cmin ↓ 21%
With RAL 1200 mg Once Daily:
  • RAL AUC ↓ 14% and ↔ Cmin
Dose
Do not coadminister. In Patients Without INSTI Resistance:
  • DTG 50 mg BID
In Patients With Certain INSTI-Associated Resistancea or Clinically Suspected INSTI Resistance:
  • Consider alternative combination.
Do not coadminister. Standard doses
ETR PK Data ↓ BIC expected ETR 200 mg BID plus DTG 50 mg Once Daily:
  • DTG AUC ↓ 71% and Cmin ↓ 88%
ETR 200 mg BID with (DRV 600 mg plus RTV 100 mg) BID and DTG 50 mg Once Daily:
  • DTG AUC ↓ 25% and Cmin ↓ 37%
ETR 200 mg BID with (LPV 400 mg plus RTV 100 mg) BID and DTG 50 mg Once Daily:
  • DTG AUC ↑ 11% and Cmin ↑ 28%
↑ or ↓ EVG, COBI, ETR possible ETR 200 mg BID plus RAL 400 mg BID:
  • ETR Cmin ↑ 17%
  • RAL Cmin ↓ 34%
Dose Do not coadminister. Do not coadminister ETR and DTG without concurrently administering ATV/r, DRV/r, or LPV/r.

In Patients Without INSTI Resistance:
  • DTG 50 mg once daily with ETR (concurrently with ATV/r, DRV/r, or LPV/r)
In Patients With Certain INSTI-Associated Resistancea or Clinically Suspected INSTI Resistance:
  • DTG 50 mg BID with ETR (concurrently with ATV/r, DRV/r, or LPV/r)
Do not coadminister. RAL 400 mg BID

Coadministration with RAL 1200 mg once daily is not recommended.
NVP PK Data
↓ BIC expected With DTG 50 mg Once Daily:
  • DTG AUC ↓ 19% and Cmin ↓ 34%
↑ or ↓ EVG, COBI, NVP possible No data
Dose
Do not coadminister. Standard doses Do not coadminister. Standard doses
RPV PK Data
No data With DTG 50 mg Once Daily:
  • DTG AUC ↔ and Cmin ↑ 22%
  • RPV AUC ↔ and Cmin ↑ 21%
↑ or ↓ EVG, COBI, RPV possible ↔ RPV RAL Cmin ↑ 27%
Dose
Standard doses Standard doses Do not coadminister. Standard doses
PIs
ATV/c PK Data BIC AUC ↑ 305% No data No data No data
Dose Do not coadminister. Standard doses Do not coadminister. Standard doses
ATV
+/-
RTV
PK Data
BIC AUC ↑ 310% Unboosted ATV plus DTG 30 mg Once Daily:
  • DTG AUC ↑ 91% and Cmin ↑ 180%
(ATV 300 mg plus RTV 100 mg) Once Daily plus DTG 30 mg Once Daily:
  • DTG AUC ↑ 62% and Cmin ↑ 121%
↑ or ↓ EVG, COBI, ATV possible With Unboosted ATV:
  • RAL AUC ↑ 72%
With Unboosted ATV and RAL 1200 mg:
  • RAL AUC ↑ 67%
With (ATV 300 mg plus RTV 100 mg) Once Daily:
  • RAL AUC ↑ 41%
Dose
Do not coadminister. Standard doses Do not coadminister. Standard doses
DRV/c PK Data
BIC AUC ↑ 74% DRV/c plus DTG Once Daily:
  • ↔ DTG, DRV, COBI
DTG 50 mg Once Daily and DRV/r Once Daily Switched to DRV/c:
  • DTG Cmin ↑ 100%
DRV/c plus EVG/c:
  • ↓ EVG possible
No data
Dose
Standard doses Standard doses Do not coadminister. Standard doses
DRV/r
PK Data
No data (DRV 600 mg plus RTV 100 mg) BID with DTG 30 mg Once Daily:
  • DTG AUC ↓ 22% and Cmin ↓ 38%
↑ or ↓ EVG, COBI, DRV possible With (DRV 600 mg plus RTV 100 mg) BID:
  • RAL AUC ↓ 29% and Cmin ↑ 38%
Dose
Standard doses Standard doses Do not coadminister. Standard doses
LPV/r PK Data
No data With (LPV 400 mg plus RTV 100 mg) BID and DTG 30 mg Once Daily:
  • ↔ DTG
↑ or ↓ EVG, COBI, LPV possible

RTV and COBI have similar effects on CYP3A.
↓ RAL

↔ LPV/r
Dose
Consider alternative combination. Standard doses Do not coadminister. Standard doses
TPV/r
PK Data
↓ BIC possible With (TPV 500 mg plus RTV 200 mg) BID and DTG 50 mg Once Daily:
  • DTG AUC ↓ 59% and Cmin ↓ 76%
↑ or ↓ EVG, COBI, TPV possible

RTV and COBI have similar effects on CYP3A.
With (TPV 500 mg plus RTV 200 mg) BID and RAL 400 mg BID:
  • RAL AUC ↓ 24% and Cmin ↓ 55%
Dose
Do not coadminister. In Patients Without INSTI Resistance:
  • DTG 50 mg BID
In Patients With Certain INSTI-Associated Resistancea or Clinically Suspected INSTI Resistance:
  • Consider alternative combination.
Do not coadminister. RAL 400 mg BID

Coadministration with RAL 1200 mg once daily is not recommended.
a Refer to DTG product labeling for details.

Key to Symbols:
↑ = increase
↓ = decrease
↔ = no change

Key to Acronyms: ARV = antiretroviral; ATV = atazanavir; ATV/c = atazanavir/cobicistat; ATV/r = atazanavir/ritonavir; AUC = area under the curve; BIC = bictegravir; BID = twice daily; Cmin = minimum plasma concentration; COBI = cobicistat; CYP = cytochrome P; DOR = doravirine; DRV = darunavir; DRV/c = darunavir/cobicistat; DRV/r = darunavir/ritonavir; DTG = dolutegravir; EFV = efavirenz; ETR = etravirine; EVG = elvitegravir; EVG/c = elvitegravir/cobicistat; INSTI = integrase strand transfer inhibitor; LPV = lopinavir; LPV/r = lopinavir/ritonavir; NNRTI = non-nucleoside reverse transcriptase inhibitor; NVP = nevirapine; PI = protease inhibitor; PK = pharmacokinetic; RAL = raltegravir; RPV = rilpivirine; RTV = ritonavir; TPV = tipranavir; TPV/r = tipranavir/ritonavir

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