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.
Efficacy and Tolerability of Lamivudine Plus Dolutegravir Compared With Lamivudine Plus Boosted PIs in HIV-1 Positive Individuals With Virologic Suppression: A Retrospective Study From the Clinical PracticeA Borghetti et al. BMC Infect Dis 19 (1), 59. PMID 30654739.In real practice, a switch to lamivudine+dolutegravir showed similar efficacy but longer durability than a switch to lamivudine+bPIs.
Pharmacokinetic Interaction of Riociguat and Antiretroviral Combination Regimens in HIV-1-infected AdultsE DeJesus et al. Pulm Circ 9 (2), 2045894019848644. PMID 30997864.Riociguat, a first-in-class soluble guanylate cyclase stimulator, is approved for the treatment of pulmonary arterial hypertension (PAH), a serious potential complication …
Virologic Failure Among People Living With HIV Initiating Dolutegravir-Based Versus Other Recommended Regimens in Real-World Clinical Care SettingsRM Nance et al. J Acquir Immune Defic Syndr 81 (5), 572-577. PMID 31107299.The proportion of previously treatment-naive PLWH remaining on recommended ART regimens did not differ by regimen. The likelihood of VF was lower with dolutegravir- than …
Drug-drug Interactions of a Two-Drug Regimen of Dolutegravir and Lamivudine for HIV TreatmentD Cattaneo et al. Expert Opin Drug Metab Toxicol 15 (3), 245-252. PMID 30704313. - ReviewThe GEMINI trials have recently shown that a two-drug regimen of dolutegravir plus lamivudine was non-inferior to a three-drug regimen in HIV-infected naïve patients. Acc …
Darunavir: A Review of Its Use in the Management of HIV Infection in AdultsK McKeage et al. Drugs 69 (4), 477-503. PMID 19323590. - ReviewBoosted darunavir was generally well tolerated in patients with HIV-1 infection in clinical trials, with most events being mild to moderate in severity. At 48-week analys …