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Pharmacokinetic profiles of boosted darunavir, dolutegravir and lamivudine in aging people living with HIV.
Courlet, Perrine a; Stader, Felix b,c; Guidi, Monia a,d; Alves Saldanha, Susana a; Stoeckle, Marcel b; Cavassini, Matthias e; Battegay, Manuel b,c; Buclin, Thierry a; Decosterd, Laurent Arthur a,*; Marzolini, Catia b,c,*; the Swiss HIV Cohort Study
[Miscellaneous Article] AIDS. 34(1):103-108, January 1, 2020.

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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.