Antiretroviral Guidelines

US DHHS Guidelines with Australian commentary

Drug-Drug Interactions Overview

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

Mechanisms of Antiretroviral-Associated Drug Interactions

PK interactions may occur during absorption, metabolism, or elimination of the ARV and/or the interacting drugs. This table does not include a comprehensive list of all possible mechanisms of interactions for individual ARV drugs (e.g., transporters); however, the table lists the most common mechanisms of known interactions and focuses on absorption and CYP- and UGT1A1-mediated interactions.

Note: N/A indicates that there are no clinically relevant interactions by these mechanisms. Identified mechanisms are specific to individual ARV drugs and not combinations of ARV drugs.

AU comment: Drug-Drug Interactions

ARV Drugs by Drug Class Mechanisms That May Affect Oral Absorption of ARV Drugs Enzymes That Metabolize or are Induced or Inhibited by ARV Drugs Other Mechanisms of Known Drug Interactions
Increasing Gastric pH Cationic Chelation P-glyco-protein CYP Substrate CYP Inhibitor CYP Inducer UGT1A1
INSTIs
BIC N/A Concentration decreased by products that contain polyvalent cations (e.g., Ca, Mg, Al, Fe, Zn) Substrate 3A4 N/A N/A Substrate Inhibitor of renal transporters OCT2 and MATE1
DTG N/A Substrate 3A4 (minor) N/A N/A Substrate Inhibitor of renal transporters OCT2 and MATE1
EVG N/A N/A 3A4 N/A 2C9 Substrate N/A
RAL N/A N/A N/A N/A N/A Substrate N/A
PK Enhancers (Boosters)
COBI N/A N/A Inhibitor 3A4 3A4, 2D6 N/A N/A N/A
RTV N/A N/A Substrate, inhibitor 3A4, 2D6 3A4, 2D6 1A2, 2B6, 2C8, 2C9, 2C19 Inducer N/A
PIs
Note: When PIs are coadministered with PK enhancers (boosters), the pharmacologic properties of both agents should be considered when assessing potential drug interactions.
ATV Concentration decreased N/A Substrate, inducer, inhibitor 3A4 3A4 N/A Inhibitor OATP inhibitor
DRV N/A N/A Substrate, inducer 3A4 3A4 2C9 N/A OATP inhibitor
FPV Concentration decreased by H2 antagonist N/A Substrate, inhibitor 3A4 3A4 N/A N/A N/A
LPV N/A N/A Substrate 3A4 3A4 N/A N/A OATP inhibitor
SQV N/A N/A Substrate, inhibitor 3A4 3A4 N/A N/A OATP inhibitor
TPV N/A N/A Substrate, inducer 3A4 2D6 3A4, 1A2, 2C19 N/A OATP inhibitor
NNRTIs
DOR N/A N/A N/A 3A4, 3A5 N/A N/A N/A N/A
EFV N/A N/A N/A 2B6 (primary), 2A6, 3A4 3A4 3A4, 2B6, 2C19 N/A N/A
ETR N/A N/A N/A 3A4, 2C9, 2C19 2C9, 2C19 3A4 N/A N/A
NVP N/A N/A N/A 3A4, 2B6 N/A 3A4, 2B6 N/A N/A
RPV Concentration decreased N/A N/A 3A4 N/A N/A N/A N/A
NRTIs
ABC N/A N/A N/A N/A N/A N/A Substrate Alcohol dehydrogenase substrate
FTC N/A N/A N/A N/A N/A N/A N/A N/A
3TC N/A N/A N/A N/A N/A N/A N/A N/A
TAF N/A N/A Substrate N/A N/A N/A N/A OATP substrate
TDF N/A N/A Substrate N/A N/A N/A N/A Competition of active renal tubular secretion
ZDV N/A N/A N/A N/A N/A N/A N/A Glucuronidation
CCR5 Antagonist
MVC N/A N/A Substrate 3A4 N/A N/A N/A N/A
Fusion Inhibitor
T-20 N/A N/A N/A N/A N/A N/A N/A N/A
Key to Acronyms: 3TC = lamivudine; ABC = abacavir; Al = aluminum; ARV = antiretroviral; ATV = atazanavir; BIC = bictegravir; Ca = calcium; COBI = cobicistat; CYP = cytochrome P; DOR = doravirine; DRV = darunavir; DTG = dolutegravir; EFV = efavirenz; ETR = etravirine; EVG = elvitegravir; Fe = iron; FPV = fosamprenavir; FTC = emtricitabine; INSTI = integrase strand transfer inhibitor; LPV = lopinavir; MATE = multidrug and toxin extrusion transporter; Mg = magnesium; MVC = maraviroc; NNRTI = non-nucleoside reverse transcriptase inhibitors; NRTI = nucleoside reverse transcriptase inhibitors; NVP = nevirapine; OCT2 = organic cation transporter 2; OATP = organic anion-transporting polypeptide; PK = pharmacokinetic; PI = protease inhibitor; RAL = raltegravir; RPV = rilpivirine; RTV = ritonavir; SQV = saquinavir; T-20 = enfuvirtide; TAF = tenofovir alafenamide; TDF = tenofovir disoproxil fumarate; TPV = tipranavir; UGT = uridine diphosphate glucuronosyltransferase; ZDV = zidovudine; Zn = zinc