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

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

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

Table 19c. Drug Interactions Between Nucleoside Reverse Transcriptase Inhibitors and Other Drugs (Including Antiretroviral Agents)

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.

Table 19c. Drug Interactions Between Nucleoside Reverse Transcriptase Inhibitors and Other Drugs (Including Antiretroviral Agents)
Concomitant Drug Class/Name NRTI Effect on NRTI and/or Concomitant Drug Concentrations Dosage Recommendations and Clinical Comments
Cytomegalovirus and Hepatitis B Antivirals
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.
ZDV No significant effect Potential increase in hematologic toxicities.
Hepatitis C Antiviral Agents
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.
ZDV Ribavirin inhibits phosphorylation of ZDV Avoid coadministration if possible, or closely monitor HIV virologic response and possible hematologic toxicities.
INSTIs
DTG TAF ↔ TAF AUC No dose adjustment necessary.
TDF ↔ TDF AUC

↔ DTG AUC
No dose adjustment necessary.
RAL TDF RAL AUC ↑ 49% No dose adjustment necessary.
Narcotics/Treatment for Opioid Dependence
Buprenorphine 3TC, TDF, TAF, ZDV No significant effect No dose adjustment necessary.
Methadone ABC Methadone clearance ↑ 22% No dose adjustment necessary.
ZDV ZDV AUC ↑ 29% to 43% Monitor for ZDV-related adverse effects.
Other
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.
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.
PIs (HIV)
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 Cmin ↓ 23% to 40% (higher Cmin 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 Cmin ↓ 30% and ↔ ZDV AUC
Clinical significance unknown.
DRV/c TAF TAF 25 mg with DRV/c:
  • ↔ TAF
No dose adjustment necessary.
TDF ↑ TFV possible Monitor for TDF-associated toxicity.
DRV/r TAF TAF 10 mg with DRV/r:
  • ↔ TAF
No dose adjustment necessary.
TDF TFV AUC ↑ 22% and Cmin ↑ 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.
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 Cmin ↓ 12% to 21%
No dose adjustment necessary.
ZDV ZDV AUC ↓ 31% to 42%

↔ TPV AUC
Appropriate doses for this combination have not been established.
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; Cmin = 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

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