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Gender Inequity-Inappropriate Prescribing
for Elderly PLWH in Swiss Cohort
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We showed that two-thirds of elderly individuals enrolled in the SHCS have prescribing issues. Risk factors for inappropriate prescribing included polypharmacy, renal impairment, treatment with CNS-active drugs and female sex.
Finally, female sex constituted another risk factor. In our study, female participants tended to be more polymedicated, had a higher prevalence of renal impairment and were more frequently prescribed benzodiazepines, consistent with previous observations in uninfected elderly women.32,33 These three factors could partly explain the prescribing issues in female individuals outnumbering those in male individuals. However, other factors are contributing given that female sex was an independent risk factor in the multivariable logistic regression.
In conclusion, prescribing issues are common in elderly PLWH, consistent with reports in uninfected elderly individuals. Inappropriate prescribing represents a risk for the patient, although it should be noted that it does not necessarily lead to harm. Medication reconciliation and periodic review of prescriptions by experienced physicians, ideally as part of multidisciplinary consultations, could reduce the risk of inappropriate prescribing. However, in clinical practice, this approach can be difficult to implement due to the pressure from hospitals and healthcare systems to reduce consultation times. Finally, our study shows that female individuals are at higher risk of inappropriate prescribing, thus doctors should be careful to avoid bias and attention is needed when prescribing for women.
Being treated with CNS-active drugs was another independent risk factor for prescribing issues, mainly driven by benzodiazepines and drugs with anticholinergic properties, both considered inappropriate in elderly individuals.10,11 Benzodiazepines and other sedative-hypnotics, such as Z-drugs, can cause memory loss, falls, fractures and motor vehicle accidents. Anticholinergic drugs are associated with multiple adverse effects to which elderly people are particularly susceptible, such as memory impairment, confusion, hallucinations, constipation, urinary retention and tachycardia. Other CNS-active drugs are also best avoided in elderly people, unless strongly indicated.
As expected, our study population had a high prevalence of age-related non-HIV comorbidities, with a similar distribution to that reported in previous studies conducted in elderly uninfected individuals22,23 or elderly PLWH.23,24 Of interest, our data showed that individuals with a longer duration of HIV infection tended to have more non-HIV comorbidities, as also observed in the geriatric Italian HIV cohort GEPPO.25 This finding could partly be explained by metabolic toxicities related to the long-term exposure to ARVs, particularly the first generation of ARV drugs. HIV-related chronic immune activation could also favour the occurrence of certain comorbidities such as atherosclerotic cardiovascular disease.
Of interest, prescribing issues occurred mainly with non-HIV drugs. The limited number of HIV drugs, being prescribed by HIV specialists and on the basis of regularly updated guidelines are conditions that tend to limit the risk of error. Conversely, there is a huge selection of non-HIV drugs, which are usually prescribed separately by different healthcare providers. The principal clinician in charge of the patient is expected to keep an overview of these prescriptions and review them periodically. As expected, polypharmacy was one independent risk factor as intuitively the more drugs that are used, the greater the risk of prescribing issues. In addition, comorbidities are drivers of polypharmacy and prescribing to polymorbid patients is highly complex, requiring both knowledge and expertise. In such a context, prescribing requires more time to adequately address issues related to dosage adjustment, management of DDIs, evaluation of drug-disease interactions and the benefit-risk ratio, but time devoted to prescribing is usually too short due to tightly timed medical visits.
Renal impairment was another independent risk factor for inappropriate prescribing. Renal function progressively declines with ageing29and is usually impaired to some extent in elderly individuals, even in the absence of a specific kidney disease. About 25% of drugs on the market are principally excreted unchanged via the kidneys, thus requiring a dosage adjustment in the case of renal impairment.30However, renal function is difficult to estimate, especially in elderly people. Plasma creatinine is often used as a quick estimate, although it is well established that it does not adequately reflect the renal function in elderly individuals, whose muscle mass is reduced.31 The various formulae used to evaluate renal function, such as Cockcroft-Gault or eGFR CKD-EPI, are more valuable than plasma creatinine, yet they may provide conflicting values and remain sheer estimates.
Of interest, our study showed sex differences in the occurrence and distribution of comorbidities leaning towards a higher prevalence of comorbidities with notably more CNS, musculoskeletal and renal disorders in female compared with male participants. These differences did not relate to age since the median age of female and male participants was comparable (78.5 versus 78 years). Our observations are consistent with other analyses showing a higher prevalence of renal impairment,34 depression, anxiety, osteoarthritis and osteoporosis23in elderly female PLWH compared with elderly male PLWH. Thus, sex differences in health status may result in different patterns of health service use, including the number of care providers, thereby impacting the risk of prescribing issues. Gender has also been shown to have an effect on the patient-healthcare interaction and prescribing pattern. We showed for instance that benzodiazepines were more frequently prescribed to female than male participants (32% versus 13%). This finding is in line with observations in the general elderly Swiss population reporting a prevalence of benzodiazepine use of 25% in female individuals compared with 15% in male individuals.35 Of interest, psychotropic drugs (i.e. anxiolytics or antidepressants) have been shown to be more often prescribed to female than male individuals with similar problems and diagnoses.36,37 This observation has been attributed to the fact that women consult more and talk more about their symptoms, leading to a higher prescription rate, notably of psychotropic drugs or analgesics.38 A sex bias whereby healthcare providers tend to diagnose more disorders and prescribe more in female than in male individuals could constitute another explanation. Sex bias can also result in female patients being undertreated compared with male patients, as demonstrated for the secondary prevention of ischaemic heart disease.39
Finally, patients with low socioeconomic status have been shown to be at higher risk of receiving potentially inappropriate prescriptions.40 In our study, female participants had a lower level of education compared with male participants (mandatory school or less: 46% versus 9%).

The extent of inappropriate prescribing observed in geriatric medicine has not been thoroughly evaluated in people ageing with HIV. We determined the prevalence of and risk factors for inappropriate prescribing in individuals aged ≥75 years enrolled in the Swiss HIV Cohort Study.
Retrospective review of medical records was performed to gain more insights into non-HIV comorbidities. Inappropriate prescribing was screened using the Beers criteria, the STOPP/START criteria and the Liverpool drug-drug interactions (DDIs) database.
For 175 included individuals, the median age was 78 years (IQR 76-81) and 71% were male. The median number of non-HIV comorbidities was 7 (IQR 5-10). The prevalence of polypharmacy and inappropriate prescribing was 66% and 67%, respectively. Overall, 40% of prescribing issues could have deleterious consequences. Prescribing issues occurred mainly with non-HIV drugs and included: incorrect dosage (26%); lack of indication (21%); prescription omission (drug not prescribed although indicated) (17%); drug not appropriate in elderly individuals (18%) and deleterious DDIs (17%). In the multivariable logistic regression, risk factors for prescribing issues were polypharmacy (OR: 2.5; 95% CI: 1.3-4.7), renal impairment (OR: 2.7; 95% CI: 1.4-5.1), treatment with CNS-active drugs (OR: 2.1; 95% CI: 1.1-3.8) and female sex (OR: 8.3; 95% CI: 2.4-28.1).
Polypharmacy and inappropriate prescribing are highly prevalent in elderly people living with HIV. Women are at higher risk than men, partly explained by sex differences in the occurrence of non-HIV comorbidities and medical care. Medication reconciliation and periodic review of prescriptions by experienced physicians could help reduce polypharmacy and inappropriate prescribing in this vulnerable, growing population.

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