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.
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 |