Lopinavir and tenofovir interaction observed in non-pregnant adults altered during pregnancy

J Clin Pharm Ther. 2021 Oct;46(5):1459-1464. doi: 10.1111/jcpt.13477. Epub 2021 Jul 12.

Abstract

What is known and objective: Tenofovir exposure is increased in non-pregnant adults when tenofovir disoproxil fumarate is coadministered with lopinavir/ritonavir. In pregnant women, tenofovir exposure is decreased. Our objective is to describe the effect of lopinavir/ritonavir on tenofovir pharmacokinetics during pregnancy.

Methods: Data were collected through the International Maternal Pediatric and Adolescent AIDS Clinical Trials (IMPAACT) Network P1026s protocol. This was a nonrandomized, open-label, parallel-group and multicentre phase-IV prospective study in pregnant women with HIV. Intensive steady-state 24-h pharmacokinetic profiles were collected during the third trimester of pregnancy and postpartum. Tenofovir was measured in plasma using validated liquid chromatography-mass spectrometry method (quantification limit: 10 ng/ml). Statistical tests compared paired and between group pharmacokinetic data.

Results and discussion: In women not receiving lopinavir/ritonavir (n = 28), tenofovir AUC0-24 was 27% lower (2.2 mcg·h/ml vs 2.8 mcg·h/ml, p = 0.002) and oral clearance was 27% higher (61 L/h vs 48 L/h, p = 0.001) during the third trimester compared to paired postpartum data. In women receiving lopinavir/ritonavir (n = 10), tenofovir AUC0-24 and oral clearance were not different antepartum compared to postpartum. Women with and women without concomitant lopinavir/ritonavir displayed no significant differences in postpartum tenofovir pharmacokinetics.

What is new and conclusion: Tenofovir exposure during the third trimester was reduced compared to postpartum in pregnant women not receiving lopinavir/ritonavir, but not in pregnant women also receiving lopinavir/ritonavir. Our findings suggest that pregnancy confounds the expected decrease in tenofovir exposure with concomitant lopinavir/ritonavir in non-pregnant adults. These findings illustrate the need for drug-drug interaction studies in pregnant women as drug disposition differs significantly in pregnant women compared to non-pregnant adults.

Keywords: HIV infection; Truvada™; Viread™; drug transporters; drug-drug interaction; kaletra; kidney; lopinavir; mother-to-child transmission; nucleoside reverse transcriptase inhibitor; perinatal transmission; pharmacokinetics; pregnancy; tenofovir.

MeSH terms

  • Adolescent
  • Adult
  • Anti-HIV Agents / pharmacokinetics
  • Anti-HIV Agents / pharmacology*
  • Anti-HIV Agents / therapeutic use*
  • Area Under Curve
  • Drug Combinations
  • Drug Interactions
  • Female
  • Half-Life
  • Humans
  • Lopinavir / pharmacology*
  • Lopinavir / therapeutic use*
  • Metabolic Clearance Rate
  • Middle Aged
  • Pregnancy
  • Prospective Studies
  • Ritonavir / pharmacology*
  • Ritonavir / therapeutic use*
  • Tenofovir / pharmacokinetics*
  • Young Adult

Substances

  • Anti-HIV Agents
  • Drug Combinations
  • lopinavir-ritonavir drug combination
  • Lopinavir
  • Tenofovir
  • Ritonavir