Drug Interactions between Nucleoside Reverse Transcriptase Inhibitors and Other Drugs (Including Antiretroviral Agents)

Last Updated: October 25, 2018;

Last Reviewed: October 25, 2018

Recommendations for managing a particular drug interaction may differ depending on whether a new ARV drug is being initiated in a patient on a stable concomitant medication or whether 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.

Note: Interactions associated with ddI and d4T are not included in this table. Please refer to FDA product labels for information regarding interactions between ddI or d4T and other concomitant drugs.

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

Key to Acronyms: 3TC = lamivudine; ABC = abacavir; ART = antiretroviral therapy; ARV = antiretroviral; ATV = atazanavir; ATV/c = atazanavir/cobicistat; ATV/r = atazanavir/ritonavir; AUC = area under the curve; C_min = minimum plasma concentration; COBI = cobicistat; d4T = stavudine; ddI = didanosine; DRV/c = darunavir/cobicistat; DRV/r = darunavir/ritonavir; DTG = dolutegravir; EFV = efavirenz; EVG = elvitegravir; FDA = Food and Drug Administration; FTC = emtricitabine; HCV = hepatitis C virus; INSTI = integrase strand transfer inhibitors; LPV/r = lopinavir/ritonavir; NRTI = nucleoside reverse transcriptase inhibitor; PI = protease inhibitor; PI/c = protease inhibitor/cobicistat; PI/r = protease inhibitor/ritonavir; RAL = raltegravir; RPV = rilpivirine; RTV = ritonavir; TAF = tenofovir alafenamide; TDF = tenofovir disoproxil fumarate; TFV = tenofovir; TFV-DP = tenofovir diphosphate; TPV/r = tipranavir/ritonavir; ZDV = zidovudine

Concomitant Drug Class/Name	NRTI	Effect on NRTI and/or Concomitant Drug Concentrations	Dosage Recommendations and Clinical Comments
Adefovir	TDF	No data	Do not coadminister. Serum concentrations of TDF and/or other renally eliminated drugs may increase.
Ganciclovir, Valganciclovir	TAF, TDF	No data	Serum concentrations of ganciclovir and/or TFV may increase. Monitor for dose-related toxicities.
Ganciclovir, Valganciclovir	ZDV	No significant effect	Potential increase in hematologic toxicities.

Concomitant Drug Class/Name	NRTI	Effect on NRTI and/or Concomitant Drug Concentrations	Dosage Recommendations and Clinical Comments
Glecaprevir/ Pibrentasvir	TAF, TDF	No significant effect	No dose adjustment necessary.
Ledipasvir/ Sofosbuvir, Sofosbuvir/ Velpatasvir, Sofosbuvir/ Velpatasvir/ Voxilaprevir	TAF	No significant effect	No dose adjustment necessary.
	TDF	Ledipasvir ↑ TFV AUC 40% to 98% when TDF is given with RPV and EFV Further ↑ TFV possible if TDF is given with PIs	No dose adjustment necessary. The safety of increased TFV exposure when ledipasvir/sofosbuvir is coadministered with TDF plus a PI/r or PI/c has not been established. Consider alternative HCV or ARV drugs to avoid increased TFV toxicities. Consider using TAF in patients at risk of TDF-associated adverse events. If TDF is used in these patients, monitor for TDF toxicity. Coadministration of ledipasvir/sofosbuvir with EVG/c/TDF/FTC is not recommended.
Ribavirin	TDF	With Sofosbuvir 400 mg: ↔ TFV AUC	No dose adjustment necessary.
Ribavirin	ZDV	Ribavirin inhibits phosphorylation of ZDV	Avoid coadministration if possible, or closely monitor HIV virologic response and possible hematologic toxicities.

Concomitant Drug Class/Name	NRTI	Effect on NRTI and/or Concomitant Drug Concentrations	Dosage Recommendations and Clinical Comments
DTG	TAF	↔ TAF AUC	No dose adjustment necessary.
DTG	TDF	↔ TDF AUC ↔ DTG AUC	No dose adjustment necessary.
RAL	TDF	RAL AUC ↑ 49%	No dose adjustment necessary.

Concomitant Drug Class/Name	NRTI	Effect on NRTI and/or Concomitant Drug Concentrations	Dosage Recommendations and Clinical Comments
Buprenorphine	3TC, TDF, TAF, ZDV	No significant effect	No dose adjustment necessary.
Methadone	ABC	Methadone clearance ↑ 22%	No dose adjustment necessary.
Methadone	ZDV	ZDV AUC ↑ 29% to 43%	Monitor for ZDV-related adverse effects.

Concomitant Drug Class/Name	NRTI	Effect on NRTI and/or Concomitant Drug Concentrations	Dosage Recommendations and Clinical Comments
Atovaquone	ZDV	ZDV AUC ↑ 31%	Monitor for ZDV-related adverse effects.
Anticonvulsants Carbamazepine, oxcarbazepine, phenobarbital, phenytoin	TAF	With Carbamazepine: TAF AUC ↓ 55% ↓ TAF possible with other anticonvulsants	Coadministration is not recommended.
Antimycobacterial Rifampin	TAF	TAF AUC ↓ 55% TFV-DP (intracellular active moiety) AUC ↓ 36% TAF plus Rifampin Compared with TDF Alone: TFV-DP (intracellular active moiety) AUC ↑ 4.2-fold With Twice-Daily TAF 25 mg Compared with Once-Daily TAF without Rifampin: TAF AUC ↓ 14% TFV-DP (intracellular active moiety) AUC ↓ 24%	Coadministration is not recommended.
Antimycobacterial Rifampin	TDF	↔ AUC TFV	No dose adjustment necessary.
Rifabutin, Rifapentine	TAF	↓ TAF possible	Coadministration is not recommended.
St. John’s Wort	TAF	↓ TAF possible	Coadministration is not recommended.

Concomitant Drug Class/Name	NRTI	Effect on NRTI and/or Concomitant Drug Concentrations	Dosage Recommendations and Clinical Comments
ATV (Unboosted), ATV/c, ATV/r	TAF	TAF 10 mg with ATV/r: TAF AUC ↑ 91% TAF 10 mg with ATV/c: TAF AUC ↑ 75%	No dose adjustment necessary (use TAF 25 mg).
	TDF	With ATV (Unboosted): ATV AUC ↓ 25% and C_min ↓ 23% to 40% (higher C_min with RTV than without RTV) TFV AUC ↑ 24% to 37%	Avoid concomitant use without RTV or COBI. Dose: ATV 300 mg daily plus (RTV 100 mg or COBI 150 mg) daily when coadministered with TDF 300 mg daily If using TDF and H2 receptor antagonist in an ART-experienced patient, use ATV 400 mg daily plus (RTV 100 mg or COBI 150 mg) daily Monitor for TDF-associated toxicity.
	ZDV	With ATV (Unboosted): ZDV C_min ↓ 30% and ↔ ZDV AUC	Clinical significance unknown.
DRV/c	TAF	TAF 25 mg with DRV/c: ↔ TAF	No dose adjustment necessary.
DRV/c	TDF	↑ TFV possible	Monitor for TDF-associated toxicity.
DRV/r	TAF	TAF 10 mg with DRV/r: ↔ TAF	No dose adjustment necessary.
DRV/r	TDF	TFV AUC ↑ 22% and C_min ↑ 37%	Clinical significance unknown. Monitor for TDF-associated toxicity.
LPV/r	TAF	TAF 10 mg with DRV/r: TAF AUC ↑ 47%	No dose adjustment necessary.
LPV/r	TDF	↔ LPV/r AUC TFV AUC ↑ 32%	Clinical significance unknown. Monitor for TDF-associated toxicity.
TPV/r	ABC	ABC AUC ↓ 35% to 44%	Appropriate doses for this combination have not been established.
	TAF	↓ TAF expected	Coadministration is not recommended.
	TDF	↔ TDF AUC TPV AUC ↓ 9% to 18% and C_min ↓ 12% to 21%	No dose adjustment necessary.
	ZDV	ZDV AUC ↓ 31% to 42% ↔ TPV AUC	Appropriate doses for this combination have not been established.