Relationship of Polypharmacy to HIV RNA Suppression in People Aged ≥ 50 Years Living With HIV

MM Murray; J Lin; A Buros Stein; ML Wilcox; J Cottreau; M Postelnick; FJ Palella

Disclosures

HIV Medicine. 2021;22(8):742-749. 

In This Article

Discussion

Medical management of aging PLWH involves challenging polypharmacy issues. Polypharmacy has become almost inescapable in older PLWH with chronic comorbid medical conditions, including renal dysfunction, diabetes, hypertension and CVD, which require long-term treatment therapy. In addition, when PLWH initiate ART, DDIs and AEs can occur. Significant factors associated with a detectable plasma HIV RNA in patients aged ≥ 50 years were taking > 15 medications, pulmonary disease and a CD4 T-lymphocyte count < 200 cells/μL. More information characterizing reasons for these associations is needed. For example, pulmonary disease may cause limited mobility and the inability to attend medication appointments, thereby affecting overall medication adherence. Interestingly, patients with depression/anxiety were more likely to have undetectable plasma HIV RNA; this may be attributable to closer and more frequent follow-up with clinicians and the overall impact of medication adherence on depressive symptoms. Of note, we used 15 medications as a threshood in this analysis; selection of this value was data-driven. Previous studies may have used a lower daily medication threshold.

Previous studies have described the effects of polypharmacy among PLWH. In an observational cross-sectional study, a high degree of polypharmacy was seen in a high number of PLWH over the age of 50 years.[18] Findings in that report included an increased risk of DDIs for ART regimens that included a PI. The authors suggested that a clinican–patient discussion should occur addressing the mitigation of DDIs based on the priority of treatment for each comorbidity.[18] Another study evaluated changes in the frequency of noncommunicable diseases and polypharmacy in PLWH over the age of 50 years[19] and found that from the initial medical visit to the last medical visit noncommunicable diseases increased by 6–15 fold, concluding that aging with HIV is associated with more noncommunicable diseases and polypharmacy.[19] A multicentre, prospective study compared prescription medications, polypharmacy and potential DDIs between younger (< 65 years old) and elderly (≥ 65 years old) PLWH.[20] The majority of potential DDIs in elderly PLWH existed between ART and cardiovascular medications, while in younger PLWH potential DDIs largely involved ART and central nervous system medications. The authors noted that periodic medication reconciliation is essential to limit the risk of inappropriate prescribing.[20] A retrospective study evaluated polypharmacy in PLWH compared to the general population, and it was found that polypharmacy was more common in PLWH than in similarly aged persons in the general population.[21]

In view of the high prevalence of polypharmacy among PLWH, de-prescribing in this population has also been studied. A prospective, randomized, interventional pharmacist-led study was conducted to evaluate the Beers Criteria and Screening Tool of Older Persons' Potentially Inappropriate Prescriptions (STOPP) to assess potentially inappropriate prescribing (PIP) in older PLWH and to evaluate pharmacist interventions.[22] This study included 248 patients and found that non-HIV-related comorbidities were significant polypharmacy factors, and that the risk of PIP was significantly increased in patients who received ≥ 11 prescription drugs. Moreover, at least 69% of patients had at least one medication discontinued after a pharmacist visit, with almost 10% having six or more medications discontinued. In this same report, over 40% of patients had at least one Beers or STOPP requirement that warranted a prompt intervention at the time of the visit.[22] Another recommended tool for systematizing the deprescribing process is the Medication Regimen Complexity Index.[23] Patients at high risk of AEs because of polypharmacy should be identified and a protocol put in place to de-prescribe and assess all medications.

Liver and kidney diseases may alter the pharmacodynamics and pharmacokinetics of many drugs used by PLWH, resulting in toxicity or lack of efficacy.[7] In addition, many ARTs act on Cytochrome P450 (CYP450) hepatic enzymes, increasing pharmacokinetic complexities.[16] The dangers of increasing co-prescribed drug concentrations are mainly associated with use of PIs, which are CYP450 inhibitors. In contrast, NNRTIs, which are CYP3A4 inducers, may reduce drug concentrations of co-prescribed medications that are metabolized by CYP3A4.[16] Such interactions between ARTs and other medications can reduce patient adherence, reduce drug efficacy and increase drug-related toxicity. Interindividual drug concentration variability was high in a study of 59 PLWH taking atorvastatin.[24] Pharmacoenhanced (boosted) antiretrovirals decreased atorvastatin clearance by 58%, and ARTs that are CYP3A4 inducers increased atorvastatin clearance by 78%. Simulations of atorvastatin exposure (area under the curve) varied from a 180% increase attributable to CYP3A4 inhibition to a 44% decrease attributable to CYP3A4 induction by antiretrovirals;[24] these data suggest that, for a specific DDI, patients may have varied responses. In another DDI study, boosted darunavir clearance was 40% lower in patients ≥ 65 years old vs. those < 65 years old.[25] Additionally, the half-lives of boosted darunavir, dolutegravir and lamivudine were 148%, 45% and 32% higher in older (≥ 65 years old) vs. younger PLWH. The study concluded that the effect on boosted darunavir clearance was not clinically significant, although there was a high variability of exposure.

Limitations of this study should be considered. DDIs were assessed retrospectively, and clinical significance was not evaluated. Data regarding plasma HIV RNA levels were analysed as a single point in time. Therefore, trends over time were not assessed. The assessment of the association between number of medications received and plasma HIV RNA was also limited by the presence of confounding factors linked to HIV disease burden. The indication or appropriateness of all medications received was not considered in this analysis; therefore, it is unknown if the number of medications was appropriate for a given patient or excessive. ART therapy has evolved since these data were collected; however, most regimens recommended for PLWH remain administered once or twice daily. Therefore, the overall number of ART medications received is likely to remain the same, although the exact medications may differ.

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