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Aging in France Report
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Download the PDF here
from Jules: compare <50 vs experienced aging: "We compared 10 318 ageing patients [median age 56 years; 25% interquartile range (IQR) 53-62 years] with 13 302 younger patients (median age 42 years; 25% IQR 36-47 years)."
much more comorbidities in aging group - avg age 56 53-2, wait until average age is 65 ! - all these at much higher rates cancer, renal, heart, neuromuscular, depression, sex dysfunction, lipids abnormal, hypertension, diabetes
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Ageing with HIV: do comorbidities and polymedication drive treatment optimization?
In this large prospective cohort of French patients living with HIV, comorbidity was frequent. In the ageing population with a long HIV history, 62.1% of patients had at least one comorbidity. Dyslipidaemia, hypertension and depression were the most frequent comorbidities. Coprescriptions were similarly frequent, with 71% of the ageing population with a long HIV history receiving at least one drug class concomitant to ART, and as many as 10% of them receiving five or more drug classes. Psychiatric agents (including hypnotics) and cardiovascular drugs were the most commonly coprescribed drug classes.
In conclusion, we showed that, in a population with very frequent comorbidities and coprescriptions, physicians should be aware of the risks of toxicity and DDIs, with particular attention being paid to ageing patients with a long HIV history.
Protease inhibitor-based ART was less frequently prescribed in ageing patients and in patients with comorbidity and coprescriptions; nevertheless, it was still used in approximately 30% in each group. INSTIs were used more frequently in patients with multiple comorbidities and comedications. Although we cannot draw any inferences from this cross-sectional study, the findings emphasize that this class is often preferd when DDIs are of concern.
Multi-morbidity has been related to mortality [14], poor quality of life and greater risk of drug toxicity [4] and has already been described as increasing in the ageing HIV-infected population [8]. Some of these comorbidities may be induced or aggravated by ART [15-18]. It is of growing importance for HIV physicians to limit the use of these drugs and to provide counselling for healthy ageing, with particular attention to patients ageing with a long HIV history, as they represent a distinct group from those who have seroconverted while ageing [3].
Only 37.9% of the "experienced ageing" population did not have any comorbidity, compared with 67.5% of the younger group and 44.1% of the "recently diagnosed ageing" population. Table 2 shows details of the comorbidities for the total population and the comparisons between groups. Among the patients with at least one comorbidity, ART was based on a bPI in 31.2% of the patients (vs. 34.8% of the patients with no comorbidity), on an NNRTI in 29.7% (vs. 38.6%, respectively), on an INSTI in 10.3% (vs. 6.2%, respectively), and on another regimen in 28.8% (vs. 20.4%, respectively) (P < 0.0001).
Table 4 shows the proportions of patients who had been treated with INSTI-based ART with regard to the presence of a specific comorbidity or comedication, independent of patient group. The proportion of INSTI-experienced patients increased from 17.1% in the absence of comorbidity to 47.2% in the case of five or more comorbidities. Similarly, the proportions of INSTI-experienced patients increased from 14.3% of patients receiving no comedication to 34.2% of patients receiving five or more drugs along with their ART.
Among 23683 HIV-infected patients fulfilling the inclusion criteria, 10318 were > 50 years old and represent the ageing group (median age 56 years; 25% IQR 53-62 years), and 13302 were ≤ 50 years old and represent the younger group (median age 42 years; 25% IQR 36-47 years). Among the ageing group, 7025 patients were diagnosed with HIV infection before 2000 and constituted the "experienced ageing" population. The characteristics of the overall population and the comparisons between the groups are summarized in Table 1. Ageing patients were more frequently male than younger patients: 77% of the ageing group vs. 65% of the younger group were male. Notably, the "experienced ageing" patients had been treated for twice as long as the "recently diagnosed ageing" and younger populations. On the censoring date, 28.2% of the "experienced ageing" patients were receiving triple ART based on a bPI (vs. 39% and 36.5% of the younger and "recently diagnosed ageing" populations, respectively), 27% were receiving an NNRTI (vs. 33% and 38%, respectively), 9% were receiving an INSTI (vs. 7% and 9%, respectively), and 35.8% were receiving another regimen (fewer or more than three drugs) (vs. 21% and 16.5%, respectively) (P < 0.0001).
There were statistically significant differences between the groups in the percentage of patients not receiving any comedication: only 29.2% of the "experienced ageing" population, 47.2% of the younger group and 33.4% of the "recently diagnosed ageing" group were not receiving any comedication. Table 3 shows details of comedications for the total population and the comparisons between groups. Among the patients receiving at least one comedication, ART was based on a bPI in 32.8% of the patients (vs. 38.5% of the patients with no comedication), on an NNRTI in 30.6% (vs. 32.8%, respectively), on an INSTI in 9.3% (vs. 5.1%, respectively), and on another regimen in 27.3% (vs. 23.5%, respectively) (P < 0.0001).
Among the 2939 patients with HCV infection, 20% of the population were spontaneously cured, with no difference between the age groups. Among the HCV treatment-naïve patients, patients refusal and medical contra-indication were more frequent in the ageing group than in the younger group (17 vs. 9%, respectively; P < 0.0001). Among the patients with past HCV treatment (54% of the ageing group vs. 49% of the younger group; P < 0.0001), no difference between the age groups was found in the treatment results. Overall, 42% of the treated patients had sustained HCV suppression, and 58% were in need of new HCV treatment.
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Ageing with HIV: do comorbidities and polymedication drive treatment optimization?
First published: 7 October 2016
HIV Medicine
L Cuzin,1,2,3 C Katlama,4,5 L Cotte,6,7 P Pugliese,8 A Cheret,9,10,11 C Bernaud,12 D Rey,13 I Poizot-Martin,14,15 C Chirouze,16,17 F Bani-Sadr18,19 and A Cabie20,21 for the DatAIDS Study Group
1INSERM, UMR 1027, Toulouse, France, 2Toulouse III University, Toulouse, France, 3COREVIH, CHU Toulouse, Toulouse, France, 4UPMC Univ Paris 06, UMR_S 1136, Pierre Louis Institute of Epidemiology and Public Health, Sorbonne Univ, Paris, France, 5Infectious Diseases Department, Pitie Salp^etriere, AP-HP, Paris, France, 6Infectious Diseases Department, Hospices Civils de Lyon, Lyon, France, 7INSERM U1052, Lyon, France, 8Infectious Diseases Department, CHU Archet, Nice, France, 9EA 3620, Universite Paris-Descartes, Sorbonne Paris Cite, Paris, France, 10Infectious Diseases Department, Tourcoing General Hospital, Tourcoing, France, 11Internal Medicine Unit, Bic^etre Hospital, AP-HP, Paris, France, 12Infectious Diseases Department, CHU Hotel Dieu, Nantes, France, 13Le Trait dUnion, HIV care Center, CHU Strasbourg, Strasbourg, France, 14Immuno-Hematology Clinic, APHM H^opital Sainte-Marguerite, Aix-Marseille Univ, Marseille, France, 15Inserm U912 (SESSTIM), Marseille, France, 16UMR CNRS 6249 Chrono- Environnement, Franche-Comte University, Besancon, France, 17Infectious Diseases Department, Besancon University Hospital, Besancon, France, 18EA-4684/SFR CAP-SANTE, Reims Champagne-Ardenne University, Reims, France, 19Tropical and Infectious Diseases, H^opital Robert Debre, CHU Reims, Reims, France, 20Infectious Diseases Department, Universite Antilles, Guyane, EA 4537 and 21Franch West Indies University, Fort de France, France
Objectives
The aim of the study was to describe the ageing HIV-infected population (> 50 years old) and their current antiretroviral therapy (ART), comorbidities and coprescriptions in France in 2013 and to compare them to the younger population.
Methods
A retrospective analysis of a prospectively collected database was performed. The characteristics of patients receiving ART as well as their current ART and their numbers of comorbidities and comedications at the censoring date (1 July 2013) were compared between patients ageing with HIV infection, patients who seroconverted while ageing, and younger patients.
Results
We compared 10 318 ageing patients [median age 56 years; 25% interquartile range (IQR) 53-62 years] with 13 302 younger patients (median age 42 years; 25% IQR 36-47 years).
The ageing patients were more frequently male than the younger patients (77 vs. 65%).
Among the ageing patients, 7025 were diagnosed with HIV infection before 2000 and represented a distinct group, the experienced ageing group, by comparison with the recently diagnosed ageing group.
Triple therapy containing a boosted protease inhibitor was used in 28.2% of the patients (vs. 39% and 36% of the younger and "recently diagnosed ageing" groups, respectively); a nonnucleoside reverse transcriptase inhibitor in 27% (vs. 33% and 38%, respectively), an integrase strand transfer inhibitor (INSTI) in 9% (vs. 7% and 9%, respectively), and another regimen (fewer or more than three drugs) in 35.8% (vs. 21% and 16.5%, respectively).
"Experienced ageing" patients typically had one or more comorbidities (62.1%) and were receiving at least one comedication (71%).
Central nervous system (CNS) agents (prescribed in 44.6% of the "experienced ageing" patients) and antilipidaemics (in 44.2%) were the most frequently prescribed comedications.
INSTIs were used in 23% of the population and were used significantly more often in patients with comorbidities and coprescriptions. For all comparisons, P < 0.0001.
Conclusions
In ageing HIV-infected patients, especially those with a long history of HIV infection, comorbidities and coprescriptions are highly prevalent.
Introduction
Since potent antiretroviral therapy (ART) became available, HIV-related mortality has been steadily decreasing in high-income countries [1]. Compared with the general population, the relative risk of death is no longer elevated in French HIV-infected individuals successfully treated with ART [2]. As a direct consequence, the HIV-infected population in care is ageing. In France, the percentage of HIV-infected patients 50 years of age or older increased from 8.5 to 42% for men and from 6 to 27% for women between 2003 and 2012 [2]. Moreover, this ageing population is diverse, including patients diagnosed while ageing and patients diagnosed many years ago and ageing with HIV infection [3].
A North American study found that multi-morbidity was present in 65% of HIV-infected patients [4], and, as in the general population, multiple chronic conditions accumulated with increasing age [5]. Because of this comorbidity, a wide variety of drugs (e.g. antidepressants or statins) are prescribed along with antiretroviral drugs. However, the combination of these drugs produces a high potential for drug-drug interactions (DDIs) that may result in either loss of efficacy or increased toxicity of the respective drugs. In a recent Spanish study, 292 potential DDIs were found in 268 patients, mainly involving boosted protease inhibitors (bPIs), benzodiazepines, nonsteroidal anti-inflammatory drugs, nonnucleoside reverse transcriptase inhibitors (NNRTIs), corticosteroids, proton pump inhibitors and antithrombotics [6]. In the same study, it was found that clinically significant interactions were strongly related to the use of ritonavir-boosted PIs because of the mixed inducer/inhibitor effects of ritonavir on different cytochrome P450 pathways [7]. Thus, an important issue in the future will be the optimal management of multi-morbidity and multidrug exposure [8]. Integrase strand transfer inhibitors (INSTIs), a new well-tolerated ART class with metabolic properties driving few DDIs [9, 10], at least for those who do not need a pharmacological booster, have recently become available and their use may be beneficial in the ageing population to avoid DDIs.
Using a large prospective French database, we described the ageing population, the prevalence of various comorbidities and the prescription of comedications, and the choice of ART regimens.
Discussion
In this large prospective cohort of French patients living with HIV, comorbidity was frequent. In the ageing population with a long HIV history, 62.1% of patients had at least one comorbidity. Dyslipidaemia, hypertension and depression were the most frequent comorbidities. Coprescriptions were similarly frequent, with 71% of the ageing population with a long HIV history receiving at least one drug class concomitant to ART, and as many as 10% of them receiving five or more drug classes. Psychiatric agents (including hypnotics) and cardiovascular drugs were the most commonly coprescribed drug classes.
Protease inhibitor-based ART was less frequently prescribed in ageing patients and in patients with comorbidity and coprescriptions; nevertheless, it was still used in approximately 30% in each group. INSTIs were used more frequently in patients with multiple comorbidities and comedications. Although we cannot draw any inferences from this cross-sectional study, the findings emphasize that this class is often preferd when DDIs are of concern.
Multi-morbidity has been related to mortality [14], poor quality of life and greater risk of drug toxicity [4] and has already been described as increasing in the ageing HIV-infected population [8]. Some of these comorbidities may be induced or aggravated by ART [15-18]. It is of growing importance for HIV physicians to limit the use of these drugs and to provide counselling for healthy ageing, with particular attention to patients ageing with a long HIV history, as they represent a distinct group from those who have seroconverted while ageing [3].
Polypharmacy is of growing interest in patients ageing with HIV infection [6, 7, 19-21]. In another prospective European cohort [22], the same proportion of patients receiving comedications was described, highlighting the ongoing potential for serious DDIs in HIV practice as a result of polypharmacy. Actually, in a study specifically designed to look for DDIs, Evans-Jones et al. found that 27% of the studied prescriptions could lead to DDIs, with a risk for a potential reduction of ART efficacy in 15% of cases [23].
Ritonavir-boosted PIs were shown to be frequently associated with relevant DDIs in a study in which the authors emphasized that there is a great opportunity for pharmacists to become more involved by applying their knowledge in helping the physician to optimize treatments [6]. Interestingly, the Work Group for the HIV and Aging Consensus Project, among other recommendations, stresses that the primary care provider should perform an annual medication review to limit toxicity and DDIs and that we should recommend that our patients use one pharmacy and, if possible, use an HIV specialty pharmacy [19]. Hence, a multidisciplinary approach to ART management, including physicians, virologists and pharmacists, is recommended in France to prevent the risk of DDIs and to optimize clinical management [24].
INSTIs began being used in 2009 [25], with confirmed good efficacy and tolerance in ART-naïve patients [26]. Furthermore, replacing bPIs with raltegravir has been shown to be virologically noninferior and to improve the patients lipid profiles [27]. The availability of new drugs in the INSTI class offers an opportunity to reduce drug and pill burdens for our patients, at least when using INSTIs that do not need a pharmacological booster.
We analysed a large, prospective, multicentre cohort of more than 23600 patients in care in France, including overseas territories, enabling us to describe a substantial group of ageing patients. Because of the population size, we were able to distinguish ageing patients with a long HIV history from those who seroconverted while ageing. Nevertheless, our study has some limitations. Some coprescriptions may have been underestimated, as the physician may not feel it necessary to write them on the patients medical chart. Notably, cancer chemotherapy, which was prescribed by other specialized physicians, was clearly absent from our database. However, this underestimation reinforces our findings. This cross-sectional retrospective analysis of our database did not allow us to assess the multifactorial cause of any ART modification, and thus the growing use of INSTIs with comorbidities and coprescriptions may not be related to the analysed issues. Nevertheless, our results seem to be consistent with some degree of willingness to reduce toxicity and potential DDIs.
In conclusion, we showed that, in a population with very frequent comorbidities and coprescriptions, physicians should be aware of the risks of toxicity and DDIs, with particular attention being paid to ageing patients with a long HIV history.
Methods
Information was collected from 11 large HIV reference centres in France. These hospitals maintain prospective databases of all HIV-1-infected patients who seek care in the centres and provide written consent. The data collection has been approved by the French National Commission on Informatics and Liberty (CNIL). The databases are implemented via an electronic medical record (EMR) [11]. The patients enter the databases when they seek care in one of the centres, regardless of their HIV disease history, and all previous clinical events as well as therapeutic history are collected with the appropriate dates. The EMR collects demographic details, clinical events, antiretroviral history, viral load and CD4 T-cell count data for patients at regular 3- to 6-month intervals during routine clinical assessment. This system allows the use of the databases with minimal delay, limited to automatic and manual quality controls required before any analysis.
For the purposes of this study, we selected all patients on ART who presented to at least one medical visit between 1 January 2009 and 1 July 2013 (the censoring date). The collected demographic characteristics were sex, the most probable route of HIV acquisition, and CD4 T-cell count and viral load value before starting ART. Age, body mass index (BMI), the presence of hepatitis C virus (HCV) coinfection, Centers for Disease Control and Prevention (CDC) class, total ART duration and current regimen were collected at the censoring date. In the case of HCV coinfection, history of HCV treatment was also collected. Unfortunately, the databases do not collect socioeconomic characteristics such as social isolation, employment status, education level or receipt of financial welfare.
The medical history was searched to collect data on past or current diabetes, hypertension, dyslipidaemia, cardiovascular diseases, neurovascular diseases, depression, cancer, and sexual dysfunction. Renal insufficiency was defined by an estimated glomerular filtration rate <60 ml/min/1.73 m², as calculated using the Modification of Diet in Renal Disease (MDRD) formula. The patients medical prescriptions were searched for concomitant use of medications with potential DDIs when used with ART. We retained the following drug classes, using the Anatomical Therapeutic Chemical classification [12]: nonsteroidal anti-inflammatories (NSAIs), corticosteroids, vitamin K antagonists, tuberculosis treatments, cardiovascular drugs, cancer chemotherapy, fibrates, statins, post-transplant immunosuppressive agents, proton pump inhibitors, psychiatric medications (including hypnotics), and erectile dysfunction treatments.
Patients were classified as "ageing" if they were > 50 years old at the censoring date. To distinguish those recently diagnosed from those with long-term ART experience, the "recently diagnosed ageing" group was composed of ageing patients with an HIV diagnosis made after 2000, in contrast to ageing patients diagnosed before 2000, who were defined as "experienced ageing" patients. Their characteristics, comorbidities and coprescriptions were compared with those of patients who were ≤ 50 years old. Because INSTIs that do not require cobicistat or ritonavir pharmacological boosters are responsible for fewer DDIs than other ART classes [13], we also analysed the proportions of patients who received an INSTI across diverse comorbidities and comedications. As a consequence of the study period used, raltegravir was the only INSTI that we could consider. Continuous variables were described by their medians and 25% interquartile ranges (IQRs) and compared between groups using a Mann-Whitney test. Categorical variables were described by proportions and compared using chi-squared tests.
Results
Among 23683 HIV-infected patients fulfilling the inclusion criteria, 10318 were > 50 years old and represent the ageing group (median age 56 years; 25% IQR 53-62 years), and 13302 were ≤ 50 years old and represent the younger group (median age 42 years; 25% IQR 36-47 years). Among the ageing group, 7025 patients were diagnosed with HIV infection before 2000 and constituted the "experienced ageing" population. The characteristics of the overall population and the comparisons between the groups are summarized in Table 1.
Ageing patients were more frequently male than younger patients: 77% of the ageing group vs. 65% of the younger group were male. Notably, the "experienced ageing" patients had been treated for twice as long as the "recently diagnosed ageing" and younger populations. On the censoring date, 28.2% of the "experienced ageing" patients were receiving triple ART based on a bPI (vs. 39% and 36.5% of the younger and "recently diagnosed ageing" populations, respectively), 27% were receiving an NNRTI (vs. 33% and 38%, respectively), 9% were receiving an INSTI (vs. 7% and 9%, respectively), and 35.8% were receiving another regimen (fewer or more than three drugs) (vs. 21% and 16.5%, respectively) (P < 0.0001).
Among the 2939 patients with HCV infection, 20% of the population were spontaneously cured, with no difference between the age groups. Among the HCV treatment-naïve patients, patients refusal and medical contra-indication were more frequent in the ageing group than in the younger group (17 vs. 9%, respectively; P < 0.0001). Among the patients with past HCV treatment (54% of the ageing group vs. 49% of the younger group; P < 0.0001), no difference between the age groups was found in the treatment results. Overall, 42% of the treated patients had sustained HCV suppression, and 58% were in need of new HCV treatment.
Only 37.9% of the "experienced ageing" population did not have any comorbidity, compared with 67.5% of the younger group and 44.1% of the "recently diagnosed ageing" population. Table 2 shows details of the comorbidities for the total population and the comparisons between groups. Among the patients with at least one comorbidity, ART was based on a bPI in 31.2% of the patients (vs. 34.8% of the patients with no comorbidity), on an NNRTI in 29.7% (vs. 38.6%, respectively), on an INSTI in 10.3% (vs. 6.2%, respectively), and on another regimen in 28.8% (vs. 20.4%, respectively) (P < 0.0001).
There were statistically significant differences between the groups in the percentage of patients not receiving any comedication: only 29.2% of the "experienced ageing" population, 47.2% of the younger group and 33.4% of the "recently diagnosed ageing" group were not receiving any comedication. Table 3 shows details of comedications for the total population and the comparisons between groups. Among the patients receiving at least one comedication, ART was based on a bPI in 32.8% of the patients (vs. 38.5% of the patients with no comedication), on an NNRTI in 30.6% (vs. 32.8%, respectively), on an INSTI in 9.3% (vs. 5.1%, respectively), and on another regimen in 27.3% (vs. 23.5%, respectively) (P < 0.0001).
Table 4 shows the proportions of patients who had been treated with INSTI-based ART with regard to the presence of a specific comorbidity or comedication, independent of patient group. The proportion of INSTI-experienced patients increased from 17.1% in the absence of comorbidity to 47.2% in the case of five or more comorbidities. Similarly, the proportions of INSTI-experienced patients increased from 14.3% of patients receiving no comedication to 34.2% of patients receiving five or more drugs along with their ART.
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