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Pharmacokinetics of Antiretroviral Drugs in Older People Living with HIV: A Systematic Review

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Abstract

Background and objective

The life expectancy of people living with HIV (PLWHIV) has significantly improved in recent decades, mostly due to antiretroviral (ARV) therapy. Aging can affect the pharmacokinetics of drugs and, as a consequence, increase the risk of drug interactions and toxicity that may impact treatment. The aim of this study was to carry out a systematic review of the literature on the effect of aging on ARV pharmacokinetics.

Methods

Searches were performed in the BVS, EMBASE and PUBMED databases until November 2022. All studies available in English, Spanish and Portuguese investigating the pharmacokinetics of ARV approved by the US Food and Drug Administration (FDA) from 2005 to 2020 were selected. Peer-reviewed publications were included if they met all criteria: adults (≥ 18 years of age) living with or without HIV; report any pharmacokinetic parameter or plasma concentration of at least one of the following ARVs: tenofovir alafenamide fumarate (TAF); doravirine (DOR), rilpivirine (RIL) and etravirine (ETR); darunavir (DRV), tipranavir (TPV) and fostemsavir (FTR); dolutegravir (DTG), raltegravir (RAL), bictegravir (BIC) and elvitegravir (EVG); maraviroc (MVC); ibalizumab (IBA); cobicistat (COBI). Pharmacokinetic parameters were reported stratified per age group: young adults (aged 18–49 years) or older (age ≥ 50 years) and all studies were evaluated for quality. The review protocol was registered in the PROSPERO database (registration number CRD42021236432).

Results

Among 97 studies included, 20 reported pharmacokinetic evaluation in older individuals (age ≥ 50 years). Twenty five percent of the articles were phase I randomized clinical trials with HIV-negative participants and non-compartmental pharmacokinetic analysis presenting the parameters area under the curve (AUC) and peak drug concentration (Cmax). Seven age-stratified studies evaluated BIC, ETR, DRV, DTG, DOR and RAL. We found publications with discordant results for ETR and DTG pharmacokinetics in different age groups. DRV exposure was highly variable but modestly increased in aging PLWHIV. In contrast, no influence of age on BIC, DOR and RAL exposure was observed. A variability in pharmacokinetic parameters could be observed for the other ARVs (TAF and MVC) in different age groups.

Conclusion

Exposure to DRV increases modestly with age, while exposure to BIC, DOR and RAL appears to be unaffected by age. As the available evidence to confirm a potential effect of aging on ARV pharmacokinetics is limited, further studies are necessary.

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Authors and Affiliations

  1. Sérgio Arouca National School of Public Health, ENSP Fiocruz, Rio de Janeiro, RJ, Brazil

    Thainá Toledo & Rita Estrela

  2. Evandro Chagas National Institute of Infectious Diseases, INI Fiocruz, Rio de Janeiro, Brazil

    Thales Castro, Vanessa G. Oliveira, Valdilea Gonçalves Veloso, Beatriz Grinsztejn, Sandra Wagner Cardoso, Thiago S. Torres & Rita Estrela

  3. Faculty of Pharmacy, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil

    Rita Estrela

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This work was supported by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior-CAPES-Finance Code 001, and by the Carlos Chagas Filho Foundation for Research Support in the State of Rio de Janeiro (FAPERJ) [E-26/010.101.009/2018]. BG and TST were funded by the National Council of Technological and Scientific Development (CNPq) and FAPERJ.

Conflicts of interest

Thainá Toledo, Thales Castro, Vanessa G. Oliveira, Valdilea Gonçalves Veloso, Beatriz Grinsztejn, Sandra Wagner Cardoso, Thiago S. Torres, and Rita Estrela declare no competing interests.

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RE and TST conceived the study. The literature search and data analysis were performed by TT, RE, TST, TC, and VGO. TT drafted the manuscript and RE, TST, TC, VGO, SWC, VGV and BG critically revised the work.

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Toledo, T., Castro, T., Oliveira, V.G. et al. Pharmacokinetics of Antiretroviral Drugs in Older People Living with HIV: A Systematic Review. Clin Pharmacokinet 62, 1219–1230 (2023). https://doi.org/10.1007/s40262-023-01291-x

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