Liverpool HIV Interactions

Potential Weak Interaction

Tenofovir-DF (TDF)

Dolutegravir/Abacavir/ Lamivudine (DTG/ABC/3TC)

Quality of Evidence: Very Low

Summary:

Triumeq (dolutegravir, abacavir, lamivudine) can be used as a complete regimen for the treatment of HIV-1 infection. However, in specific clinical situations where an intensification of HIV treatment is needed, coadministration with tenofovir-DF would be possible from a pharmacokinetic standpoint. No clinically significant pharmacokinetic interaction was observed between tenofovir-DF and dolutegravir, abacavir or lamivudine. Coadministration of tenofovir-DF (300 mg once daily) and dolutegravir (50 mg once daily) decreased dolutegravir Cmax and Ctrough by 3% and 8%, and increased AUC by 1%. Tenofovir Cmax, AUC and Ctrough increased by 9%, 12% and 19%, respectively. No significant pharmacokinetic interaction was observed when tenofovir-DF (300 mg once daily) and lamivudine (150 mg twice daily for 7 days) were coadministered. There was no change in AUC, Cmax or Cmin of tenofovir. Lamivudine AUC and Cmin were unaltered, and there was a 24% decrease in Cmax. Coadministration of tenofovir-DF (300 mg once daily) and abacavir (300 mg single dose) had no effect on tenofovir AUC or Cmax, and abacavir AUC; abacavir Cmax increased by 12%.

Description:

Coadministration of dolutegravir and tenofovir increased dolutegravir AUC by 1% and decreased Cmax and Ctrough by 3% and 8%. There was no effect on tenofovir. No dose adjustment is necessary when Triumeq is combined with nucleoside reverse transcriptase inhibitors.

Triumeq Summary of Product Characteristics, ViiV Healthcare, June 2019.

In drug interaction trials, dolutegravir did not have a clinically relevant effect on the pharmacokinetics of tenofovir. Tenofovir had no clinically significant effect on the pharmacokinetics of dolutegravir. Coadministration of tenofovir-DF (300 mg once daily) and dolutegravir (50 mg once daily) was studied in 15 subjects. Dolutegravir Cmax and Ctrough decreased by 3% and 8%, and AUC increased by 1%. Tenofovir Cmax, AUC and Ctrough increased by 9%, 12% and 19%, respectively.

Triumeq US Prescribing Information, ViiV Healthcare, May 2019.

Coadministration of dolutegravir (50 mg once daily) and tenofovir-DF (300 mg once daily) was studied in 15 HIV-negative subjects. The pharmacokinetic parameters of tenofovir and dolutegravir when coadministered were comparable to those when given alone, demonstrating no significant drug interaction. Dolutegravir AUC increased by 1%, but Cmax and Ctrough decreased by 3% and 8%, respectively. Tenofovir AUC, Cmax and Ctrough increased by 12%, 9% and 19%, respectively.

Lack of interaction between the HIV integrase inhibitor S/GSK1349572 and tenofovir in healthy subjects. Song I, Min SS, Borland J, et al. J AIDS, 2010, 55(3): 365-367.

The plasma and intracellular pharmacokinetic interaction between tenofovir and abacavir, lamivudine or lopinavir was investigated in HIV+ subjects receiving TDF + 3TC/LPV (n=7), TDF + 3TC/NVP (n=8), TDF + ABC/LPV (n=7) or TDF + ABC/NVP (n=5). Between group comparisons showed no significant interaction between tenofovir and abacavir or lamivudine.

A pharmacokinetic study in HIV infected patients under tenofovir fumarate: investigation of systemic and intracellular interaction between TDF and abacavir, or lamivudine or lopinavir/ritonavir. Pruvost A, et al. 8th International Workshop on Clinical Pharmacology of HIV Therapy, Budapest, April 2007, abstract 56.

The effect of stopping abacavir on the intracellular pharmacokinetics of tenofovir was studied in 7 HIV-infected subjects initially receiving abacavir and tenofovir with lamivudine or stavudine. Intracellular levels of tenofovir-diphosphate did not demonstrate evidence of substantial changes over time after discontinuation of abacavir. Median TDF-DP concentrations prior to and 1 month after discontinuation were 89.9 and 89.6 fmol/10^6 cells, respectively.

Intracellular pharmacokinetics of tenofovir disphosphate, carbovir triphosphate and lamivudine triphosphate in patients receiving triple-nucleoside regimens. Hawkins T, et al. J Acquir Immune Defic Syndr, 2005, 39: 406-411.

View all available interactions with Tenofovir-DF (TDF) by clicking here.