The challenge of HIV treatment in an era of polypharmacy

Abstract

Introduction: The availability of potent antiretroviral therapy has transformed HIV infection into a chronic disease such that people living with HIV (PLWH) have a near normal life expectancy. However, there are continuing challenges in managing HIV infection, particularly in older patients, who often experience age-related comorbidities resulting in complex polypharmacy and an increased risk for drug-drug interactions. Furthermore, age-related physiological changes may affect the pharmacokinetics and pharmacodynamics of both antiretrovirals and comedications thereby predisposing elderly to adverse drug reactions. This review provides an overview of the therapeutic challenges when treating elderly PLWH (i.e. >65 years). Particular emphasis is placed on drug-drug interactions and other common prescribing issues (i.e. inappropriate drug use, prescribing cascade, drug-disease interaction) encountered in elderly PLWH.

Discussion: Prescribing issues are common in elderly PLWH due to the presence of age-related comorbidities, organ dysfunction and physiological changes leading to a higher risk for drug-drug interactions, drugs dosage errors and inappropriate drug use.

Conclusions: The high prevalence of prescribing issues in elderly PLWH highlights the need for ongoing education on prescribing principles and the optimal management of individual patients. The knowledge of adverse health outcomes associated with polypharmacy and inappropriate prescribing should ensure that there are interventions to prevent harm including medication reconciliation, medication review and medication prioritization according to the risks/benefits for each patient.

Keywords: HIV; ageing; comorbidities; drug-drug interactions; polypharmacy; prescribing issues.

Figure 1

Evaluating the drug‐drug interaction potential of a drug. PBPK, physiologically based pharmacokinetic modelling.

Figure 2

Mechanisms of drug‐drug interactions with antiretroviral drugs. Victim means that the exposure of the antiretroviral drug can be increased or decreased by a comedication with inhibitory or inducing properties on drug‐metabolizing enzymes or drug transporters. Conversely, perpetrator means that the antiretroviral drug inhibits and/or induces drug‐metabolizing enzymes and/or transporters and therefore can alter the exposure of the coadministered drug. Figure reproduced from reference 84 with permission from the journal Taylor & Francis (https://tandfonline.com). c, cobicistat; PI, protease inhibitor; r, ritonavir; TAF, tenofovir alafenamide; TDF, tenofovir disoproxil fumarate.

Figure 3

Drug‐drug interaction profiles of selected antiretroviral drugs. Percentage of green, yellow, amber and red DDIs considering 750 comedications listed in the Liverpool HIV interaction website 83 for selected antiretroviral drugs belonging to the protease inhibitor (PI), integrase inhibitor (INI) and non‐nucleoside reverse transcriptase inhibitor (NNRTI) classes. BIC, bictegravir; DRV/c, darunavir boosted with ritonavir; DRV/r, darunavir boosted with ritonavir; DOR, doravirine; DTG, dolutegravir; EVG/c, elvitegravir boosted with cobicistat; EFV, efavirenz; ETV, etravirine; RAL, raltegravir; RPV, rilpivirine.