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Farmacia Hospitalaria

On-line version ISSN 2171-8695Print version ISSN 1130-6343

Farm Hosp. vol.44 n.4 Toledo Jul./Aug. 2020  Epub June 28, 2021

https://dx.doi.org/10.7399/fh.11367 

ORIGINALS

Prevalence of polypharmacy and pharmacotherapy complexity in elderly people living with HIV in Spain. POINT study

Mercedes Gimeno-Gracia1  2  , Javier Sánchez-Rubio-Ferrández3  , María de las Aguas Robustillo-Cortés4  , Ramón Morillo-Verdugo4 

1Department of Pharmacy, Hospital Clínico Universitario Lozano Blesa, Zaragoza. Spain.

2IIS Institute for Health Research Aragon, Zaragoza. Spain.

3Department of Pharmacy, Hospital Universitario de Getafe, Getafe. Spain.

4Department of Pharmacy, Hospital Universitario Nuestra Señora de Valme, Sevilla. Spain.

Abstract

Objective:

To determine the prevalence of polypharmacy in persons living with HIV of at least 65 years of age receiving antiretroviral treatment. A characterization of antiretroviral treatment, as well as a determination of the prevalence of comorbidities; of the most common types of concomitant medication; of adherence rates; of the pharmacotherapeutic complexity; and of drug-drug interactions were also among the goals of the study.

Method:

This was a multi-center, cross-sectional observational study that included persons living with HIV aged 65 years or more who were on active antiretroviral treatment. Demographic, clinical (viral load, CD4 count and comorbidities) and pharmacotherapeutic (type of antiretroviral treatment: single tablet regimen, polypharmacy (six active ingredients or more) and major polypharmacy (11 active ingredients or more) variables were considered). Adherence to antiretroviral treatment was measured by dispensation records and the Simplified Medication Adherence Questionnaire, while adherence to concomitant medication was measured using dispensation records and the Morisky-Green questionnaire. The Medication Regimen Complexity Index was calculated. Drug-drug interactions were analyzed using the Liverpool and Lexicomp databases.

Results:

Seventy-four patients (86.5% male) were included, with a median age of 69 years (66.7-72.0). The sexual route was the most common route of transmission of the disease (67.6%). The virus was undetectable in 89.2% of patients; the CD4 count was over 200/mL in 94.6% of the sample. The median number of comorbidities was 3.5 (2.0-5.0), 52.7% of them being cardiovascular; 50.0% related to the central nervous system; 17.6% hepatic; and 8.1% consisting in chronic pulmonary disease. A total of 81.1% of patients received triple therapy and 48.6% single tablet regimen. The median number of concomitant drugs administered was 5.0 (2.0-7.0), polypharmacy was observed in 71.6% of cases and major polypharmacy in 25.7%. Antihypertensive and cardiovascular drugs were prescribed to 56.8% of patients, lipid-lowering drugs to 50.0%, antiulcer agents to 33.8% and psychoactive drugs to 32.4%. According to dispensation records, adherence to antiretroviral treatment was 85.1% and to concomitant medication 62.8%. The median Medication Regimen Complexity Index for the whole treatment was 13.0 (8.0-17.6). Potential drug-drug interactions were observed in 55.4% of patients and contraindicated interactions in 12.2%.

Conclusions:

Elderly persons living with HIV exhibit a high prevalence of polypharmacy, pharmacotherapeutic complexity, poor adherence and drug-drug interactions. For that reason, pharmacotherapeutic optimization must be a priority in these patients.

KEYWORDS: Polypharmacy; HIV; Pharmacotherapeutic complexity; Age

Resumen

Objetivo:

Determinar la prevalencia de polifarmacia en personas que viven con VIH de al menos 65 años en tratamiento antirretroviral. Describir el tratamiento antirretroviral, determinar la prevalencia de comorbilidades, el tipo de medicación concomitante más frecuente, la adherencia, la complejidad farmacoterapéutica y las interacciones.

Método:

Estudio observacional, transversal y multicéntrico en el que se incluyeron a personas que viven con VIH de al menos 65 años con tratamiento antirretroviral activo. Se recogieron variables demográficas, clínicas (carga viral, linfocitos CD4 y comorbilidades) y farmacoterapéuticas (tipo de tratamiento antirretroviral, regímenes con single-tablet-regimen, polifarmacia -seis principios activos incluyendo tratamiento antirretroviral-, polifarmacia mayor -11 principios activos incluyendo tratamiento antirretroviral-). Se midió la adherencia al tratamiento antirretroviral con los registros de dispensación y con el Simplified Medication Adherence Questionnaire, y la adherencia al tratamiento concomitante mediante los registros de dispensación y el cuestionario Morisky-Green. Se calculó el índice de complejidad farmacoterapéutica a través del Medication Regimen Complexity Index. Se revisaron las interacciones con la base de datos de Liverpool y Lexicomp.

Resultados:

Se incluyeron 74 pacientes (86,5% hombres) con una mediana de edad de 69 (66,7-72,0) años. La vía sexual fue la forma más frecuente de adquisición (67,6%). Presentaron indetectabilidad del virus e 89,2% de los pacientes y con una cifra de linfocitos CD4 de más de 200/ml el 94,6%. La mediana de comorbilidades fue de 3,5 (2,0-5,0): cardiovascular 52,7%, sistema nervioso central 50,0%, hepática 17,6% y enfermedad pulmonar crónica 8,1%. Recibieron triple terapia el 81,1% y single-tablet-regimen el 48,6%. La mediana de fármacos concomitantes fue 5,0 (2,0-7,0), polifarmacia 71,6% y polifarmacia mayor 25,7%. Medicamentos antihipertensivos y del sistema cardiovascular fueron prescritos en un 56,8% de los pacientes, hipolipemiantes 50,0%, antiulcerosos 33,8% y psicofármacos 32,4%. La adherencia según registros de dispensación del tratamiento antirretroviral fue del 85,1% y de la medicación concomitante del 62,8%. La mediana del Medication Regimen Complexity Index del tratamiento completo fue 13,0 (8,0-17,6). Tenían al menos una interacción potencial el 55,4% y al menos una contraindicada el 12,2% de los pacientes.

Conclusiones:

Las personas mayores que viven con VIH tienen una alta prevalencia de polifarmacia, complejidad farmacoterapéutica, baja adherencia al tratamiento e interacciones, por lo que la optimización farmacoterapéutica debe ser una prioridad en este tipo de pacientes.

PALABRAS CLAVE: Polifarmacia; VIH; Complejidad farmacoterapéutica; Edad

Introduction

HIV infection is currently regarded as a chronic disease thanks to the extraordinary reduction in mortality achieved following the introduction of highly active antiretroviral treatment (ART) and the subsequent advent of more powerful and easy-to-manage therapeutic regimens. Increased survival has resulted in increasing numbers of patients reaching old age1. Estimations suggest that, by 2030, 73% of HIV patients will be over 50 years of age2. Similarly to the general population, ageing in HIV patients leads to the development of concomitant conditions. These comorbidities have been shown to appear earlier in patients living with HIV than in the general population3,4. An analysis of the DAD cohort (Data Collection on Adverse Events of Anti-HIV Drugs)5 demonstrated a prevalence of 33% of hyperglyceridemia, 22% of hypercholesterolemia, 8% of hypertension and 3% of diabetes mellitus, among other comorbidities6.

The development of concomitant conditions is associated to an increased use of drugs. Several studies have shown that the number of concomitant medications increases significantly after the age of 507,8. This increase could have a negative effect on the patients' adherence to ART, which is a key factor in controlling the disease9.

Different studies have shown that aging is capable of altering virtually all pharmacokinetic processes occurring in the human body, including absorption, first-pass metabolism, bioavailability, distribution, protein binding and hepatic and renal clearance. These alterations play a role in increasing the risk of developing medication-related problems10.

Polypharmacy, which has been defined as the concurrent use of six or more medications11, has become a significant public health problem, particularly in elderly care. Maher et al.12 showed that polypharmacy is associated to negative clinical results and the development of adverse reactions, occurrence of drug-to-drug interactions, use of inappropriate drugs, appearance of malnutrition, worsening of function, falls, fractures and hospital admissions13-15. The Consensus Paper on Old Age and HIV Infection sets at age 50 the cut off point for defining old age in this population. Indeed, there is evidence that HIV causes premature ageing of the immune system and the first signs of impairment of the immune response become apparent at that age. Moreover, the Consensus Paper defines HIV patients aged 65 or over as very elderly11.

Although a few polypharmacy studies on PLWH (people living with HIV) have been performed in Spain16, no representative data are as yet available on elderly persons living with HIV.

The main goal of this study is to determine the prevalence of polypharmacy in elderly PLWH subjected to ART and pharmacotherapeutic monitoring in outpatient pharmacy clinics in Spanish hospitals. Specifically we set about determining the prevalence of comorbidities; describing the different types of ART administered; defining the most commonly used concomitant medication; calculating the prevalence of polypharmacy and major polypharmacy; analyzing the adherence associated to polypharmacy; studying pharmacotherapeutic complexities; and identifying the prevalence of drug-to-drug interactions in the population under study.

Methods

This paper consists in a sub-analysis of the POINT project, whose main purpose was to determine the prevalence of polypharmacy in PLWH receiving ART and subjected to pharmacotherapeutic monitoring at outpatient pharmacy clinics in Spanish hospitals. It is a multi-center cross-sectional observational study that included PLWH aged 65 years and over who were on active ART and were dispensed their antiretroviral medication by the pharmacy department of the participating hospitals on the day on which the cross-sectional sample was drawn (February 2017). The Spanish Drug Agency classified the POINT study as a “post-authorization study using designs other than prospective follow-up”. POINT was authorized by the Ethics Committee of the Sevilla Sur Health District. Its full title was Prevalencia, factores asociados y complejidad farmacoterapéutica de la polifarmacia en pacientes VIH en España (Prevalence, prevalence-related factors and pharmacotherapeutic prevalence of polypharmacy in HIV patients in Spain).

Exclusion criteria were as follows: patients admitted on the day the study was carried out, patients included in clinical trials and those failing to sign the informed consent form.

The demographic variables analyzed were sex and age. Clinical variables included route of acquisition of the HIV infection, viral load and CD4 count, and comorbidities (liver disease (HBV, HCV), central nervous system disease, cardiovascular disease or hypertension, and chronic pulmonary disease (COPD or asthma)) at the time of the study. Comorbidity patterns were classified into cardio-metabolic, pycho-geriatric, mechanico-thyroid or combined, which required for at least two conditions to be present. Other variables analyzed included pharmacotherapeutic variables, type of ART administered (triple-therapy, dual-therapy or other combinations), types of STR (single-tablet-regimen) treatment, and concomitant medication prescribed (obtained from the patients' clinical record and clinical interview). Polypharmacy was defined as the simultaneous prescription of six active ingredients, including those used for ART. Major polypharmacy was defined as the concomitant use of 11 active ingredients or more11. Patients were classified according to their polypharmacy pattern: cardiovascular, depressive-anxious, pulmonary disease, or combined. To fall into one of those categories, patients had to have been prescribed at least three drugs belonging to the same category.

Adherence to ART and to concomitant medication was measured using the dispensation records of the last six months. The SMAQ and Morisky-Green questionnaires were also used, the former for ART and the latter for the concomitant medication. Patients were considered adherent if the possession rate for the relevant medication was over 95% for ART and over 90% for the concomitant medication. The respective questionnaire had to yield a positive result.

Pharmacotherapeutic complexity was calculated using the MRCI (Medication Regimen Complexity index) index, proposed by George et al.17.

This index allows calculation of medication complexity, considering the following three criteria: dosage form, frequency of dosing and additional administration instructions.

The overall complexity of the medication prescribed was recorded during the data collection process and during the interview leading to the study. In addition, a quantitative and qualitative analysis was made of the complexity of the different subsections making up the MRCI index.

Drug-to-drug interactions, including contraindicated interactions, were evaluated using the Liverpool HIV Pharmacology Group website (www.hiv-druginteractions.com) and the Lexicomp database.

Statistical analysis

At first, a statistical refinement of the data was performed. The resulting data were then individually processed. Quantitative variables were expressed either as means (standard deviation), or through medians and percentiles (P25 and P75) in the case of asymmetrical distributions. Qualitative variables were expressed by frequencies and percentages.

Data were analyzed using the IBM SPSS 20.0 software package for Windows.

Results

Eighty-one hospitals from all 17 Spanish regions participated in the study. In total, 74 PLWH were recruited (86.5% were male), of whom 71.6% were on polypharmacy and 25.6% on major polypharmacy. The median of concomitant drugs prescribed stood at 5.0 (interquartile range (IQR) 2-7). Table 1 shows the socio-demographic and clinical characteristics of patients in the study.

Table 1.  Demographic and clinical characteristics of persons living with HIV in the study 

CNS: central nervous system; COPD: chronic obstructive pulmonary disease; CV: cardiovascular; HT: hypertension; IQR: interquartile range.

Fifty PLWH had a comorbidity pattern; in 58.0% it was cardio-metabolic, in 12.0% psycho-geriatric, in 6.0% mechanico-thyroid, and in 24.0% combined.

As regards ART regimens, the most frequently prescribed combinations were: two nucleoside/nucleotide-analog reverse transcriptase inhibitors (NRTi's) plus an integrase strand transfer inhibitor (INSTI) (39.2%), and one non-nucleoside analog reverse transcriptase inhibitor (NNRTI) (35.1%). The most frequently used NRTIs, NNRTIs, protease inhibitors (PIs) and INSTIs were abacavir/lamivudine (75.4%), rilpivirine (46.9%), darunavir (92.9%) and dolutegravir (65.8%) respectively. A total of 81.1% of the population received triple therapy, 10.8% received dual-therapy and 4.1% monotherapy. Only 4.1% of the population received other combinations. STR was administered to 48.6% of patients.

Table 2 shows the ART regimens administered under the study.

A total of 56.8% of PLWH were on antihypertensive and cardiovascular medications (C1 to C9 on the ATC classification system); 50.0% were on lipid-lowering agents; 33.8% on antiulcer drugs; 32.4% on psychoactive agents (anxiolytics and antidepressants (N05, N06)); 29.7% on anti-diabetic medication (A10); 10.8% on COPD drugs (R03); 5.4% on antiepileptic agents; and 2.7% on Parkinson's disease medication.

Table 2.  Antiretroviral treatment 

3TC: lamivudine; ABC: abacavir; COB: cobicistat; DRV: darunavir; DTG: dolutegravir; EFV: efavirenz; ELV: elvitegravir; FTC: emtricitabine; NVP: nevirapine; RAL: raltegravir; RPV: rilpivirine; RTV: ritonavir; TAF: tenofovir alafenamide; TDF: tenofovir disoproxil fumarate.

PLWH were classified according to their polypharmacy pattern, which was cardiovascular in 25.7% of patients, depressive-anxious in 5.4%; chronic respiratory in 5.4% and combined in 2.7%. No prevailing pattern was found in 60.8% of subjects.

The percentage of PLWH that adhered to their ART was 85.1% when calculated on the basis of dispensation records, and 68.5% when the SMAQ questionnaire was used for the calculation. The percentage of PLWH who adhered to their concomitant medication was 62.8% when calculated based on dispensation records, and 65.6% when the Morisky-Green questionnaire was used for the calculation.

The median medication complexity score for the entire regimen (ART + concomitant medication) was 13.0 (IQR 8.0-17.6), with the highest levels of complexity being associated with the dose frequency of the concomitant treatment (Figure 1).

Figure 1.  Median medication regimen complexity score (calculated using MRCI). 

As regards drug-to-drug interactions, 55.4% of PLWH developed at least one potential interaction, and 12.2% at least one contraindicated interaction. The total number of interactions identified was 110 (97 potential interactions and 13 contraindicated interactions, see Table 3), with a mean of 2.6 (2.4) interactions per patient. Pharmacokinetic interactions occurred more frequently (71.8%) than pharmacodynamic ones. Interactions resulted mainly from changes in the metabolism of the drugs (63.3%) and from impaired absorption of the drugs into the body (26.6%). Interactions between the drugs in the ART regimen and the drugs taken concomitantly by the patients (76.6%) were more common than those between concomitant medications.

The NNRTI agent was the antiretroviral agent most commonly involved in drug-to-drug interactions (40.7%), followed by the PI agent (29.6%). The concomitant drugs most usually involved in interactions were statins, oral antidiabetics, urological agents and mineral supplements, with rates of 22.7%, 9.1%, 7.3% and 6.4%, respectively.

Table 3.  Contraindicated interactions 

Discussion

This cross-sectional study revealed a very high prevalence of polypharmacy and pharmacotherapeutic complexity in PLWH older than 65 years receiving ART in Spain.

The most common comorbidity pattern for the studied population was the cardio-metabolic one, which coincides with the findings of the GEPPO cohort, a large Italian geriatric cohort where dyslipidemia, hypertension and cardiovascular disease are the most frequently occurring comorbidities18. As a result, the predominant polypharmacy pattern was the cardiovascular one, in line with the findings published in previous studies7.

Most patients in the studied cohort were on triple therapy ART and 48.6% were receiving STR. This diverges from the findings by Guaraldi19 where STR regimens were typically administered to younger patients, and LDR (less drug regimen) monotherapy and dual combination therapy were administered to older patients. In contrast to Guaraldi et al., where the most common STR regimens were efavirenz/emtricitabine/tenofovir and rilpivirine/emtricitabine/tenofovir, in our cohort most patients received abacavir/ lamivudine/dolutegravir. This difference could be due to the fact that Guaraldi et al. were unable to avail themselves of the latter combination. The low prevalence of LDR in our population is remarkable, considering that the use of monotherapy and dual combination therapy is one of the preferred strategies for elderly patients to decrease polypharmacy, potential drug-todrug interactions and their consequences20.

The polypharmacy and major polypharmacy rates (71.6% and 25.7%, respectively) observed in the PLWH in our study are somewhat higher than those in the Italian21, Canadian22 and English23 cohorts. These differences may be due to the definition of polypharmacy used. That said, prevalence was high in all the studies mentioned.

Polypharmacy is associated with poorer adherence to ART9. In the population studied, adherence to ART was 85.1% when measured based on the dispensation record, and 68.5% when measured against the SMAQ questionnaire. This disparity is due to the fact that each method has its limitations, each of them yielding a different adherence rate. Adherence to concomitant medication, for its part, was lower than for ART. With the above-mentioned ART adherence rates, viral load was undetectable for 90.9% of patients. This raises questions as to the level of adherence needed to reach viral suppression, which could be drug-dependent and lower than what is generally believed, as suggested by Byrd et al.24.

Higher treatment complexity is associated to a higher likelihood of non-adherence and a higher admission risk; it also often increases after hospital admission25-27. For that reason, reducing complexity would seem to entail significant benefits for the patient. It would appear that, in the subjects in our cohort, a reduction of the MRCI could be achieved by enhancing the dosage of the concomitant medication, as this was the element that contributed the most to the complexity index. Moreover, an MRCI score of 11.25 has recently been found to be the threshold for predicting polypharmacy in PLWH28. We will henceforth have to bear in mind that threshold when identifying our patients and trying to improve their medication regimen.

As regards drug-to-drug interactions, polypharmacy has been shown to be associated to a higher probability of developing an interaction29. This was precisely the case with our population, where 12.2% of PLWH exhibited at least one contraindicated interaction, almost twice as many as in the study by Bastida et al.29 which despite being single-center shows similar results to Greene et al.30.

The main limitation of this study was its cross-sectional design, well suited to quantify polypharmacy but not to identify predictive factors. The size of the sample was small given the characteristics of the study. There was also a limitation related to the methods used to measure adherence which, in spite of their compound nature (questionnaire + dispensations record), are rather inaccurate. The main strengths of the study include its multi-center nature and the fact that it included patients from all 17 Spanish regions.

Future studies should focus on finding ways of reducing polypharmacy and pharmacotherapeutic complexity in elderly PLWH. A set of or bin or bing guidelines for non-ART therapy in HIV patients has been recently published31. This document could be used as a basis for developing specific programs targeted to elderly patients with HIV.

In summary, this study shows how elderly PLWH are characterized by high levels of polypharmacy and pharmacotherapeutic complexity, as well as or adherence to concomitant medications, and a high risk of experiencing drug-to-drug interactions. These results should facilitate the development of pharmacotherapeutic intervention and optimization strategies for these kinds of patients. (Table 4, Table 5, Table 6)

Table 4.  Participating study centers 

Table 5.  Participating study centers (cont.) 

Table 6.  Participating study centers (cont.) 

Contribution to the scientific literature

The chief practical contribution of this study is that it provides data on the prevalence of polypharmacy, its associated factors, and pharmacotherapeutic complexity in elderly persons living with HIV in Spain. The data provided herein can be used as a basis for the development of intervention and pharmacotherapeutic optimization strategies for patients on polypharmacy requiring intensive monitoring.

References

Gueler A, Moser A, Calmy A, Günthard HF, Bernasconi E, Furrer H, et al.; Swiss HIV Cohort Study, Swiss National Cohort. Life expectancy in HIV-positive persons in Switzerland: matched comparison with general population. AIDS. 2017;31:427-36. DOI: 10.1097/QAD.0000000000001335 [ Links ]

Smith M, Brinkman K, Geerlings S, Smit C, Thyagarajan K, Sighem Av, et al.; ATHENA observational cohort. Future challenges for clinical care of an ageing population infected with HIV: a modelling study. Lancet Infect Dis. 2015;15:810-8. DOI: 10.1016/S1473-3099(15)00056-0 [ Links ]

Guaraldi G, Orlando G, Zona S, Menozzi M, Carli F, Garlassi E, et al. Premature age-related comorbidities among HIV-infected persons compared with the general population. Clin Infect Dis. 2011;53:1120-6. DOI: 10.1093/cid/cir627 [ Links ]

Schouten J, Wit FW, Stolte IG, Kootstra NA, van der Valk M, Geerlings SE, et al.; AGEhIV Cohort Study Group. Cross-sectional comparison of the prevalence of age-associated comorbidities and their risk factors between HIV-Infected and uninfected individuals: the AGEhIV cohort study. Clin Infect Dis. 2014;59:1787-97. DOI: 10.1093/cid/ciu701 [ Links ]

D:A:D Study Group, Sabin CA, Worm SW, Weber R, Reiss P, El-Sadr W, et al. Use of nucleoside reverse transcriptase inhibitors and risk of myocardial infarction in HIVinfected patients enrolled in the D:A:D study: a multicohort collaboration. Lancet. 2008;371:1417-26. DOI: 10.1016/S0140-6736(08)60423-7 [ Links ]

Gleason LJ, Luque AE, Shah K. Polypharmacy in the HIV-infected older adult population. Clin Interv Aging. 2013;8:749-63. DOI: 10.2147/CIA.S37738 [ Links ]

Marzolini C, Back D, Weber R, Furrer H, Cavassini M, Calmy A, et al.; Swiss HIV Cohort Study Members. Ageing with HIV: medication use and risk for potential drug-drug interactions. J Antimicrob Chemother. 2011;66:2107-11. DOI: 10.1093/jac/dkr248 [ Links ]

Holtzman C, Armon C, Tedaldi E, Chmiel JS, Buchacz K, Wood K, et al.; HOPS Investigators. Polypharmacy and risk of antiretroviral drug interactions among the aging HIV-infected population. J Gen Intern Med. 2013;28:1302-10. DOI: 10.1007/s11606-013-2449-6 [ Links ]

Cantudo-Cuenca MR, Jiménez-Galán R, Almeida-González CV, Morillo Verdugo R. Concurrent use of comedication reduces adherence in antiretroviral therapy among HIV patients. J Manag Care Pharm. 2014;20:844-50. DOI: 10.18553/jmcp.2014.20.8.844 [ Links ]

Mangoni AA, Jackson SHD. Age-related changes in pharmacokinetics and pharmacodynamics: basic principles and practical applications. Br J Clin Pharmacol. 2004;57:6-14. DOI: 10.1046/j.1365-2125.2003.02007.x [ Links ]

Grupo de expertos de la Secretaría del Plan Nacional sobre el sida (SPNS), Sociedad Española de Geriatría y Gerontología (SEGG). Documento consenso sobre edad avanzada e infección por el virus de la inmunodeficiencia adquirida (noviembre 2015) (accessed 11/2019). Available at: https://www.mscbs.gob.es/ciudadanos/enfLesiones/enfTransmisibles/sida/publicaciones/profSanitarios/docEdadAvanzadaVIH.pdfLinks ]

Maher RL, Hanlon J, Hajjar ER. Clinical consequences of polypharmacy in elderly. Expert Opin Drug Saf. 2014;13:57-65. DOI: 10.1517/14740338.2013.827660 [ Links ]

Field TS, Gurwitz JH, Harrold LR, Rothschild J, DeBellis KR, Seger AC, et al. Risk factors for adverse drug events among older adults in the ambulatory setting. J Am Geriatr Soc. 2004;52:1349-54. DOI: 10.1111/j.1532-5415.2004.52367.x [ Links ]

Fialová D, Topinková E, Gambassi G, Finne-Soveri H, Jónsson PV, Carpenter I, et al.; AdHOC Project Research Group. Potentially inappropriate medication use among elderly home care patients in Europe. JAMA. 2005;293:1348-58. DOI: 10.1001/jama.293.11.1348 [ Links ]

Tseng A, Szadkowski L, Walmsley S, Salit I, Raboud J. Association of age with polypharmacy and risk of drug interactions with antiretroviral medications in HIV positive patients. Ann Pharmacother. 2013;47:1429-39. DOI: 10.1177/1060028013504075 [ Links ]

López-Centeno B, Badenes-Olmedo C, Mataix-Sanjuan A, McAllister K, Bellón JM, Gibbons S, et al. Polypharmacy and drug-drug interactions in HIV-infected subjects in the region of Madrid, Spain: a population-based study. Clin Infect Dis. 2019 20 Ago. DOI: 10.1093/cid/ciz811 [ Links ]

George J, Phun YT, Bailey MJ, Kong DC, Stewart K. Development and validation of the medication regimen complexity index. Ann Pharmacother. 2014;38:1369-76. DOI:10.1345/aph.1D479 [ Links ]

Nozza S, Malagoli A, Maia L, Calcagno A, Focà E, De Socio G, et al. Antiretroviral therapy in geriatric HIV patients: the GEPPO cohort study. J Antimicrob Chemother. 2017;72:2879-86. DOI: 10.1093/jac/dkx169 [ Links ]

Guaraldi G, Menozzi M, Zona S, Calcagno A, Silva AR, Santoro A, et al. Impact of polypharmacy on antiretroviral prescription in people living with HIV. J Antimicrob Chemother. 2017;72:511-4. DOI: 10.1093/jac/dkw437 [ Links ]

Guaraldi G, Marcotullio S, Maserati R, Gargiulo M, Milic J, Franconi I, et al. The management of geriatric and frail HIV patients. A 2017 update from the Italian guidelines for the use of antiretroviral agents and the diagnostic-clinical management of HIV-1 infected persons. J Frailty Aging. 2019;8:10-6. DOI: 10.14283/jfa.2018.42 [ Links ]

Guaraldi G, Malagoli A, Calcagno A, Mussi C, Celesia BM, Carli F, et al. The increasing burden and complexity of multi-morbidity and polypharmacy in geriatric HIV patients: a cross sectional of people aged 65-74 years and more tan 75 years. BMC Geriatr. 2018;18:99. DOI: 10.1186/s12877-018-0789-0 [ Links ]

Krentz HB, Gill MJ. The impact of non-antiretroviral polypharmacy on the continuity of antiretroviral therapy (ART) among HIV patients. AIDS Patient Care STDS. 2016;30:1-17. DOI: 10.1089/apc.2015.0199 [ Links ]

Halloran MO, Boyle C, Kehoe E, Bagkeris E, Mallon P, Post FA, et al. Polypharmacy and drug-drug interactions in older and younger people living with HIV: the POPPY study. Antivir Ther. 2019;24:193-201. DOI: 10.3851/IMP3293 [ Links ]

Byrd KK, Hou JG, Hazen R, Kirkham H, Suzuki S, Clay PG, et al.; Patient-Centered HIV Care Model Team. Antiretroviral adherence level necessary for HIV viral suppresion using real-world data. J Acquire Immune Defic Syndr. 2019;18:245-51. DOI: 10.1097/QAI.0000000000002142 [ Links ]

Wimmer BC, Cross AJ, Jokanovic N, Wiese MD, George J, Johnell K, et al. Clinical outcomes associated with medication regimen complexity in older people: a systematic review. J Am Geriatr Soc. 2017;65:747-53. DOI: 10.1111/jgs.14682 [ Links ]

Manzano-García M, Pérez-Guerrero C, Álvarez de Sotomayor Paz M, Robustillo-Cortés MLA, Almeida-González CV, Morillo-Verdugo R. Identification of the medication regimen complexity index as an associated factor of nonadherence to antiretroviral treatment in HIV positive patients. Ann Pharmacother. 2018;52:862-7. DOI: 10.1177/1060028018766908 [ Links ]

Robustillo Cortés MA, Morillo Verdugo R, Barreiro Fernández EM, Pavón Plata A, Monje Agudo P. Influence of hospital admission in the pharmacotherapy complexity of HIV+ patients. Farm Hosp. 2017;41:518-26. DOI: 10.7399/fh.2017.41.4.10751 [ Links ]

Morillo-Verdugo R, Robustillo-Cortés MA, Abdel-Kader Martín L, Álvarez de Sotomayor Paz M, Lozano de León Naranjo F, Almeida González CV. Determination of a cutoff value for medication regimen complexity index to predict polypharmacy in HIV+ older patient. Rev Esp Quimioter. 2019; 32:458-64. [ Links ]

Bastida C, Grau A, Márquez M, Tuset M, De Lazzari E, Martínez E, et al. Polypharmacy and potential drug-drug interactions in an HIV-infected elderly population. Farm Hosp. 2017;41:618-24. DOI: 10.7399/fh.10890 [ Links ]

Greene M, Steinman MA, McNicholl IR, Valcour V. Polypharmacy, drug-drug interactions, and potentially inappropriate medications in older adults with human immunodeficiency virus infection. J Am Geriatr Soc. 2014;62:447-53. DOI: 10.1111/jgs.12695 [ Links ]

Grupo de estudio del sida (GeSIDA). Desprescripción farmacológica de la terapia no antirretroviral en pacientes con infección por VIH. Noviembre 2018 (accessed 11/2019). Available at: http://gesida-seimc.org/wp-content/uploads/2018/09/gesida_desprescripcion_farmacologica_de_la_terapia_no_antirretroviral_en_pacientes_con_infeccion_por_VIH.pdfLinks ]

Received: November 20, 2019; Accepted: March 03, 2020

Author of correspondence Email: mgimenogr@salud.aragon.es (Mercedes Gimeno Gracia).

Conflict of interest Mercedes Gimeno García received financial support from Beca de investigación internacional MSD during the conduct of the study. She also received personal fees from ViiV (Advisory Board), Janssen and Gilead outside the scope of the submitted manuscript. Javier Sánchez Rubio received financial support from Beca de Investigación Internacional MSD during the conduct of the study. He also received personal fees from ViiV, Gilead and MSD outside the scope of the submitted manuscript. María de las Aguas Robustillo-Cortés received a grant from MSD during the conduct of the study. She also received personal fees from ViiV outside the scope of the submitted manuscript.

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