Higher plasma drug levels in elderly people living with HIV treated with darunavir

The proportion of elderly people living with HIV-1 (PLHIV) is rising. In older patients, comorbidities and concomitant medications are more frequent, increasing the risk of potential drug-drug interactions (PDDIs). Data on the pharmacokinetics of ART in individuals aged ≥ 65 years of age are scarce....

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Published inPloS one Vol. 16; no. 2; p. e0246171
Main Authors Tyrberg, Erika, Edén, Arvid, Eriksen, Jaran, Nilsson, Staffan, Treutiger, Carl Johan, Thalme, Anders, Mellgren, Åsa, Gisslén, Magnus, Andersson, Lars-Magnus
Format Journal Article
LanguageEnglish
Published United States Public Library of Science 04.02.2021
Public Library of Science (PLoS)
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Summary:The proportion of elderly people living with HIV-1 (PLHIV) is rising. In older patients, comorbidities and concomitant medications are more frequent, increasing the risk of potential drug-drug interactions (PDDIs). Data on the pharmacokinetics of ART in individuals aged ≥ 65 years of age are scarce. We compared plasma drug levels of ART, PDDIs, and side-effects in PLHIV aged ≥ 65 years of age, with controls ≤ 49 years of age. Patients ≥ 65 years of age and controls ≤ 49 years of age, all of whom were on stable treatment with atazanavir (ATV), darunavir (DRV), or efavirenz (EFV) were included cross-sectionally. Plasma drug levels of ART were analyzed, comorbidities, concomitant medication, adherence, and side-effects recorded, and PDDIs analyzed using drug interactions databases. Between 2013 and 2015, we included 100 individuals ≥ 65 years of age (study group) and 99 controls (≤ 49 years of age). Steady-state DRV concentrations were significantly higher in the study group than in the control group (p = 0.047). In the ATV group there was a trend towards a significant difference (p = 0.056). No significant differences were found in the EFV arm. The DRV arm had a higher frequency of reported side-effects than the ATV and EFV arms in the study group (36.7% vs. 0% and 23.8% respectively (p = 0.014), with significant differences between DRV vs. ATV, and EFV vs. ATV). Higher steady-state plasma levels of DRV and ATV (but not EFV) were found in PLHIV aged ≥ 65 years of age, compared to controls ≤ 49 years of age.
Bibliography:Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: ET has received honoraria as a speaker from Janssen. CJT and ÅM has received honoraria as speaker and/or scientific advisor from Gilead Sciences, and GlaxoSmithKline/ViiV. AT reports during the conduct of the study; personal fees from Gilead, personal fees from Janssen and personal fees from GSK /ViiV outside the submitted work. MG has received research grants from Gilead Sciences and Janssen-Cilag and honoraria as speaker and/or scientific advisor from Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline/ViiV, Janssen-Cilag, and MSD. LMA has received an unrestricted research grant from Bristol Myers Squibb. For the remaining authors none were declared. This does not alter our adherence to PLOS ONE policies on sharing data and materials.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0246171