The impact of age on antiretroviral drug pharmacokinetics in the treatment of adults living with HIV

ABSTRACT

Introduction

People living with HIV (PLWH) are aging and will receive life-long treatment: despite substantial improvement in drug efficacy and tolerability, side effects still occur and they can blunt antiretroviral treatment effectiveness. Since age may affect drug exposure and may be associated with side-effects we aimed at reviewing available data on the effect of age on antiretrovirals’ pharmacokinetics in adult patients.

Areas covered

We searched public databases and major conference proceedings for data on age and pharmacokinetics/pharmacodynamics in PLWH. We limited our review to currently used drugs and focused on population pharmacokinetics and physiologically-based pharmacokinetic modeling studies.

Expert opinion

Available evidence of a potential detrimental effect in elderly PLWH is limited by study design and small sample sizes. Careful consideration of undoubtful benefits and potential harms is advised when prescribing ARVs to geriatric patients and the knowledge of pharmacokinetics changes need to be included in the process. With the ‘greying’ of the pandemic we need studies with a specific focus on geriatric patients living with HIV that will consider specific phenotypes and associated changes (including sarcopenia).

KEYWORDS:

• Age
• elderly
• pharmacokinetics
• modeling

Declaration of interest

AC has received honoraria from Gilead, Insmed, Janssen-Cilag, MSD, Viiv and he is currently receiving research grants from Gilead and Viiv. GDP and SB have received honoraria from Abbvie, BMS, Gilead, Janssen-Cilag, MSD, Viiv. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

A peer reviewer of this manuscript discloses receiving speaker/advisory fees from Gilead, ViiV, MSD, Janssen, Cipla, Mylan & Theratechnologies. Peer reviewers on this manuscript have no other relevant financial or other relationships to disclose.

Article highlights

• People living with HIV that receive antiretroviral drugs are aging with multiple co-morbidities.

• Polypharmacy is very prevalent in elderly people living with HIV and they present a high risk of side effects and drug to drug interactions.

• Physiological aging is associated with several changes that may affect drug exposure or effect and expose elderly patients to a high interindividual variability.

• An increase in plasma exposure has been observed in several antiretroviral drugs but the clinical relevance of this is unknown.

• Studies enrolling geriatric individuals living with HIV and novel treatments (such as intramuscularly administered drugs) are needed.

This box summarizes key points contained in the article.

Additional information

Funding

This paper was not funded.