Pharmacokinetic profiles of boosted darunavir, dolutegravir and lamivudine in aging people living with HIV

AIDS. 2020 Jan 1;34(1):103-108. doi: 10.1097/QAD.0000000000002372.

Abstract

Objectives: The pharmacokinetics of antiretroviral drugs may differ in elderly people living with HIV (PLWH) because of age-related physiological changes. We aimed to assess the pharmacokinetics of several antiretroviral drugs in aging PLWH enrolled in the Swiss HIV Cohort (SHCS).

Design: Full pharmacokinetic profiling nested in a multicenter, observational, prospective cohort study. Additional collection of single point pharmacokinetic data during SHCS follow-up visits (unselected PLWH).

Methods: PLWH were eligible for the full pharmacokinetics investigation if they were over the age of 55 years, on a stable boosted darunavir-containing or dolutegravir-containing regimen. Single point measurements were prospectively collected during SHCS follow-up visits to compare antiretroviral drug exposure in aging (≥65 years) and younger (<65 years) PLWH.

Results: Nineteen PLWH with a median age of 64 years participated in the full pharmacokinetic investigations. Single point pharmacokinetic data were collected for 804 PLWH with a median age of 52 years. Boosted darunavir clearance was 40% lower in aging (≥65 years) compared with younger (<65 years) PLWH, consistent with other drugs predominantly metabolized by CYP3A. Dolutegravir exposure was similar between age groups whereas lamivudine exposure increased by 11% in aging PLWH. Median boosted darunavir, dolutegravir and lamivudine t1/2 were 148%, 45% and 32% higher in aging compared with younger PLWH.

Conclusion: Advanced age did not affect boosted darunavir exposure to a clinically significant extent despite the observed high variability in exposure. Age minimally affected dolutegravir and lamivudine exposure. Thus, dose adjustment based on age is a priori not warranted.

Publication types

  • Multicenter Study
  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Aging
  • Anti-HIV Agents / pharmacokinetics*
  • Anti-HIV Agents / therapeutic use
  • Darunavir / pharmacokinetics*
  • Darunavir / therapeutic use
  • Drug Therapy, Combination
  • Female
  • HIV Infections / drug therapy*
  • HIV Infections / virology
  • HIV Integrase Inhibitors / pharmacokinetics*
  • HIV Integrase Inhibitors / therapeutic use
  • Heterocyclic Compounds, 3-Ring / pharmacokinetics*
  • Heterocyclic Compounds, 3-Ring / therapeutic use
  • Humans
  • Lamivudine / pharmacokinetics*
  • Lamivudine / therapeutic use
  • Male
  • Middle Aged
  • Oxazines / pharmacokinetics*
  • Oxazines / therapeutic use
  • Piperazines / pharmacokinetics*
  • Piperazines / therapeutic use
  • Prospective Studies
  • Pyridones / pharmacokinetics*
  • Pyridones / therapeutic use
  • Viral Load

Substances

  • Anti-HIV Agents
  • HIV Integrase Inhibitors
  • Heterocyclic Compounds, 3-Ring
  • Oxazines
  • Piperazines
  • Pyridones
  • Lamivudine
  • dolutegravir
  • Darunavir