HIV-infected patients aged above 75years.

BACKGROUND: Little data is available on HIV-infected patients aged over 75years. METHODS: A descriptive study of HIV-infected patients aged over 75years was conducted in six hospitals of the Pays de la Loire region, France. Socio-demographic, immuno-virological, and therapeutic characteristics were collected via an electronic medical record software (Nadis®). To assess frailty, a simplified geriatric assessment was conducted during an HIV routine visit. RESULTS: Among the 3965 patients followed in the six centers, 65 (1.6%) were aged over 75years. From January to May 2016, 51 patients were included in the study: median age 78.7years, male patients 74.5%, homosexual transmission 41.2%, living at home 98% and single in 54.5% of cases, median duration of HIV infection 18.8years, median CD4 nadir 181 cells/mm3; CDC stage C 36.4%. All patients were on antiretroviral therapy and 98% of them had an HIV RNA<50c/mL; 82% of patients had at least one comorbidity and 58% at least two comorbidities. Eleven of 51 patients (21.6%) were diagnosed as at risk of frailty and 2/51 (3.9%) were considered frail. Cognitive disorders were diagnosed in 60.8%, depression in 35.3%, malnutrition in 25.5%, and vitamin D deficiency in 45.9%. CONCLUSIONS: HIV-infected patients aged above 75years are well-managed, but the prevalence of geriatric comorbidities is high.

Interest of proviral HIV-1 DNA genotypic resistance testing in virologically suppressed patients candidate for maintenance therapy.

Switch of antiretroviral therapy in virologically suppressed HIV-infected patients is frequent, to prevent toxicities, for simplification or convenience reasons. Pretherapeutic genotypic resistance testing on RNA can be lacking in some patients, which could enhance the risk of virologic failure, if resistance-associated mutations of the new regimen are not taken into account. Proviral DNA resistance testing in 69 virologically suppressed patients on antiretroviral treatment with no history of virological failure were pair-wised compared with pre-ART plasma RNA resistance testing. The median time between plasma (RNA testing) and whole blood (proviral DNA testing) was 47 months (IQR 29-63). A stop codon was evidenced in 23% (16/69) of proviral DNA sequences; these strains were considered as defective, non-replicative, and not taken into consideration. Within the non defective strains, concordance rate between plasma RNA and non-defective proviral DNA was high both on protease (194/220 concordant resistance-associated mutations=88%) and reverse transcriptase (28/37 concordant resistance-associated mutations=76%) genes. This study supports that proviral DNA testing might be an informative tool before switching antiretrovirals in virologically suppressed patients with no history of virological failure, but the interpretation should be restricted to non-defective viruses.

Ageing with HIV: do comorbidities and polymedication drive treatment optimization?

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.

[The quality of life of hypertensive patients treated with prazosin (sustained-release) or enalapril: a randomized controlled trial over 24 weeks]. / Etude de la qualité de vie des patients hypertendus traités par prazosine (cp osmotique) ou énalapril: un essai en double aveugle sur 24 semaines.

The importance of the criterion of Quality of Life (QOL) for compliance with antihypertensive drugs led us to study the QOL of 51 hypertensives receiving 2.5 mg of the new formulation of prazosin (sustained release), compared with 49 subjects treated by a converting enzyme inhibitor (enalapril 10 mg), in a double-blind randomized trial. QOL, assessed by means of a 22 item self-administered questionnaire, improved significantly with prazosin, during the 24 weeks of the trial. In the intention to treat analysis, the global score of QOL increased from 46.3 +/- 8.4 to 51.6 +/- 8.9 (p < 0.0001); the covariance analysis showed that the improvement was obtained as early as the 8th week. A similar favourable evolution was observed for anxiety, retardation and anhedonia components, computed from the same questionnaire. No significant difference in QOL evolution was found between prazosin and enalapril. Both treatments proved equivalent in respect of efficacy on blood-pressure values, and tolerance, estimated through the number of dropouts or side-effects. These results confirm the benefit to QOL of hypertensive patients of the new formulation of prazosin.

[Efficacy of and tolerance to prolonged release prazosin in patients with hypertension and non-insulin dependent diabetes]. / Etude de l'efficacité et de la tolérance de la prazosine à libération prolongée chez des patients hypertendus et diabétiques non insulinodépendants.

UNLABELLED: The treatment of hypertension represents one of the major elements of the cardiovascular prognosis in type II diabetes. Among antihypertensive drugs, alpha blockers may be interesting because of the absence of unfavourable effects on plasma glucose and lipid levels. OBJECTIVE: The aim of this study was to evaluate the effectiveness and the safety of prazosin osmotic tablet treatment in non-insulin-dependent diabetic patients with mild to moderate arterial hypertension. METHODS: After an initial 4-week-single-blind placebo period, 81 hypertensive subjects (162 +/- 11/96 +/- 5 mmHg) with type II diabetes were included in the study to receive prazosin osmotic tablet (o.t) open-label therapy at the dose of 2.5 mg/day for 12 weeks. After 4 weeks of treatment the dosage of prazosin o.t was increased to 5 mg/day if the diastolic blood pressure remained > or = 90 mmHg. RESULTS: Both supine and standing systolic and diastolic blood pressures were significantly decreased (P < 0.001) with prazosin therapy from 162 +/- 10/96 +/- 5 mmHg in supine and 160 +/- 12/95 +/- 6 mmHg in the upright position, to 149 +/- 15/86 +/- 9 mmHg and 148 +/- 16/86 +/- 9 mmHg respectively at the end of the 12-week-treatment period. There were no significant changes in the glycemic parameters (glycemia, haemoglobin A1c) during the prazosin therapy compared with baseline values. A significant decrease of triglycerides (P = 0.005), total cholesterol (P < 0.001) and LDL cholesterol (P = 0.03) levels was observed during prazosin therapy compared with the baseline measurements, whereas HDL cholesterol remained stable. Only 6% of the patients reported adverse events in relation with the study drug during the active treatment period. CONCLUSION: This study showed a significant decrease of the blood pressure in hypertensive subjects with type II diabetes after prazosin o.t treatment, without any change of glycemic parameters. Moreover, there was a favourable evolution of the lipidic parameters during the study characterised by a significant decrease of triglycerides and total and LDL cholesterol.

[Validation of the therapeutic role of amlodipine in 31,946 French hypertensive patients]. / Validation de l'intérêt thérapeutique de l'amlodipine dans une population française de 31,946 patients hypertendus traités en pratique de ville.

Amlodipine, a dihydropyridine calcium channel blocker (CCB), with a long duration of action, has been the subject of numerous controlled studies which showed its effectiveness and good tolerance in arterial hypertension in once-daily doses. We report the results of a large, multicentric, French, prospective phase IV study which evaluated the effectiveness and tolerance of amlodipine administered at a rate of 5 to 10 mg in only one daily dose. We also assess the evolution of the quality of life after 12 weeks of treatment among 31,946 hypertensive patients followed up to the ambulatory stage by general practitioners. The response rate--defined as the patients having had a reduction of 10 mmHg or more diastolic blood pressure--was 88%. The blood pressure standardization--defined by a diastolic blood pressure lower than 90 mmHg--was achieved for 70% of the patients. Amlodipine was administered in stand-alone therapy in 78% of the cases. The occurrence of an undesirable event was noted in the course of treatment in 12% of the patients and justified interruption of the treatment for 3.7% of the total population. The index average of quality of life was improved by the end of the 12-week treatment. This study carried out on a significant number of hypertensive patients (n = 31,946) under real prescription conditions confirms the efficacy and good tolerance of amlodipine, as has already been demonstrated in the preliminary developmental studies.

Double-blind, randomized, multicentre comparison of the effects of amlodipine and perindopril on 24 h therapeutic coverage and beyond in patients with mild to moderate hypertension. General Physicians Investigators' Group.

OBJECTIVE: To compare the therapeutic coverage and safety of amlodipine and perindopril in patients with mild to moderate hypertension (diastolic blood pressure > or = 90 mmHg and < or = 109 mmHg). DESIGN: A double-blind, randomized, parallel-group, multicentre study. METHODS: Following a 2-week placebo wash-out period, the patients were randomly allocated to treatment with either amlodipine at 5-10 mg once a day or perindopril at 4-8 mg once a day, for 60 days. Trough: peak ratios were calculated by two different methods (global and individualized approaches) from 24 h ambulatory blood pressure recordings made after the placebo period and after the active treatment period. Residual lowering of blood pressure after single-blind, single-dose omission was also investigated with further 24 h ambulatory blood pressure monitoring. Safety assessments were made throughout the study. RESULTS: The placebo-adjusted, global, diastolic blood pressure trough: peak ratio was 0.80 in the amlodipine group (n = 47) and 0.81 in the perindopril group (n = 49) in an intent-to-treat analysis. The corresponding global systolic blood pressure trough: peak ratio was 0.83 for amlodipine and 0.68 for perindopril. Individual trough: peak ratios were non-normally distributed. Mean (+/- SD) individual trough: peak ratios (intent-to-treat analysis) for diatolic blood pressure were 0.50 +/- 0.69 for amlodipine (median 0.42) and 0.15 +/- 3.27 for perindopril (median 0.33). In the per protocol analysis, the corresponding values were 0.50 +/- 0.72 (median 0.34) for amlodipine and 0.01 +/- 3.90 for perindopril (median 0.21). Both treatments produced comparable decreases in clinic systolic and diastolic blood pressure between days 0 and 60. Forty-eight hours after the last dose, both systolic and diastolic blood pressure were lower in amlodipine-treated patients than perindopril-treated patients. Amlodipine and perindopril were generally well tolerated. The most frequently reported adverse event was leg oedema in amlodipine-treated patients (19.1%), and coughing in perindopril-treated patients (14.3%). CONCLUSIONS: These results showed no statistically significant difference in trough: peak ratios between amlodipine and perindopril. However, the ambulatory blood pressure trough: peak ratios showed very large variations. Determination of trough: peak ratios by the conventional approach or by an individual approach can yield disparate values. After omitting one dose, a condition imitating noncompliance, blood pressure was more effectively controlled with amlodipine than with perindopril.

Compliance and antihypertensive efficacy of amlodipine compared with nifedipine slow-release.

Poor compliance is a principal cause of treatment failure in hypertensive patients. Once-daily dosing improves compliance, but 24-h antihypertensive activity should be provided. The compliance, efficacy, and safety of amlodipine and nifedipine slow-release (SR) were compared in patients with mild-to-moderate essential hypertension recruited among 24 centers in France. After a 2-week washout period, 103 patients were randomized to 12 weeks of 5 to 10 amlodipine mg once daily (n = 55) or 20 mg nifedipine SR twice daily (n = 48). Compliance was calculated by electronic drug monitoring. Efficacy was measured by ambulatory and casual BP recordings. Patients receiving amlodipine demonstrated better compliance than patients receiving nifedipine SR with respect to compliance index (the total number of doses taken divided by the total number of doses prescribed, expressed as a percentage; 98.3% v 87%; P < .0001), days on which the correct number of doses were taken (92.5% v 74.8%; P < .0001), and prescribed doses taken on schedule (88.7% v 71.6%; P < .0001). Absolute and relative therapeutic coverage were higher in patients receiving amlodipine than nifedipine SR (P < .0001). Mean SBP and DBP decreased equally in both groups, although amlodipine offered better BP control compared with nifedipine SR at specific times of day. Fewer patients had high nocturnal SBP with amlodipine (39.3%) than nifedipine SR (71.4%; P = .042). Adverse events and treatment withdrawals occurred less frequently in amlodipine-treated patients than in nifedipine SR-treated patients. Amlodipine (5 to 10 mg) once daily provides improved compliance, better 24-h BP control, and fewer adverse events than 20 mg nifedipine SR twice daily in patients with mild-to-moderate hypertension.

Acute hemodynamic effects of amlodipine 15 days after a myocardial infarction in normotensive patients treated with atenolol.

The acute hemodynamic effects of 20 mg iv amlodipine were evaluated in a placebo-controlled study in 16 normotensive patients 15 +/- 1 days after an acute myocardial infarction by covariance analysis. Atenolol was given orally for at least 1 week before the study to maintain the heart rate between 50 and 60 beats/min. All patients were given two doses of 10 mg of amlodipine, or 10 ml of a placebo twice, in i.v. infusion lasting 2 minutes each. Hemodynamic data were collected during the control period and 15 minutes after each of the two amlodipine or placebo infusions. At the time of the last measurements, 15 minutes after the second amlodipine or placebo infusion, the plasma amlodipine level was 31 +/- 16 micrograms/l and the plasma atenolol level was 773 +/- 564 mu/l in the amlodipine group versus 795 +/- 916 micrograms/l in the placebo group. There were no chronotropic, dromotropic, or inotropic effects. The main hemodynamic effect was a fall in systemic vascular resistance (1548 +/- 591 dynes.sec.cm-5 to 1176 +/- 526 dynes.sec.cm-5, p = 0.045) with decreases in aortic pressure and in the left ventricular stroke work index. The left ventricular ejection fraction was 51 +/- 12% in the placebo group and 56 +/- 15% in the amlodipine group (ns) during the control period, and did not change after infusion of placebo or amlodipine. Left ventricular compliance seemed to be enhanced by amlodipine, because the end-diastolic left ventricular volume index rose from 82 +/- 11 ml/m2 to 87 +/- 11 ml/m2 (p = 0.026) 15 minutes after the beginning of the second infusion of 10 mg of amlodipine, without any change in end-diastolic left ventricular pressure. Intravenous infusion of 20 mg of amlodipine is well tolerated 15 days after acute myocardial infarction in normotensive patients without deeply depressed left ventricular systolic function and chronically treated with atenolol. The main hemodynamic effects observed are potentially useful for such patients.

[Evaluation of amlodipine in stable effort angina. Comparison with diltiazem in terms of efficacy, tolerability and maintenance of the anti-ischemic action 24 hours after the last dose]. / Evaluation de l'amlodipine dans l'angor d'effort stable. Comparaison avec le diltiazem en termes d'efficacité, de tolérance et de maintien de l'action anti-ischémique 24 heures après la dernière prise.

83 patients were enrolled in a multicentre, randomized, open study to assess the efficacy of amlodipine in stable effort angina. Preselected patients were submitted to a one-week placebo wash-out period during which only nitrates or molsidomine were authorized. Patients were then randomized to receive either 5 mg of amlodipine as a morning dose, or 180 mg of diltiazem in three divided doses. After two weeks, the dosage was able to be increased (according to clinical efficacy) to 10 mg of amlodipine as a single dose or 240 mg of diltiazem in four divided doses. The antianginal efficacy of these two treatments was essentially evaluated in terms of the results of stress tests (ST) conducted at the end of the second week and fourth week of active treatment: and 24 hours after the last dose of the drug. The results of 63 patients who scrupulously complied with the protocol showed that amlodipine and diltiazem corrected or improved the ST parameters (time to onset and amplitude of ST depression, duration of ST, work performed). The anti-ischaemic action of amlodipine was maintained for at least 24 hours after the last dose and therefore provides better security (by covering the entire 24-hour period) and better compliance (by tolerating a dose omission of several hours).

Cardiac implications of amlodipine-dantrolene combinations.

PURPOSE: Cardiac disorders, cardiac arrest and ventricular fibrillation in the most severe cases, have been observed after the administration of dantrolene to patients treated by verapamil for coronary artery disease. This study was designed to examine the interaction of dantrolene with amlodipine, a dihydropyridine. METHODS: In 12 anaesthetized, open-chest pigs, the effects of the interaction have been studied on heart rate, atrioventricular conduction, monophasic action potential duration, intraventricular conduction time, left ventricular dP/dt max and mean blood pressure. The study was performed with normal coronary circulation and ischaemia of a large area of the left ventricule, obtained by complete occlusion of the left anterior descending coronary artery near its origin, under pacing at a constant high rate, 180 beats.min-1. The drugs were injected iv, amlodipine 0.4 mg.kg-1 first and dantrolene 3.0 mg.kg-1 20 min later in six animals and the order was reversed in the other animals. RESULTS: Sinus rate and atrioventricular conduction were not affected by amlodipine, but were slowed by dantrolene added (145 +/- 9 to 131 +/- 7 beats.min-1, P < 0.01 and 150 +/- 15 to 180 +/- 20 msec, P < 0.01). In contrast, amlodipine or amlodipine plus dantrolene did not change MAP duration or conduction time in the normal heart. Similarly, they did not alter the maximal variations due to ischaemia, but delayed them, while prolonging the time to onset of fibrillation (111 +/- 8 to 343 +/- 33 sec. P < 0.001 with amlodipine alone, 289 +/- 11 to 323 +/- 16 sec, P < 0.05 with dantrolene). Left ventricular dP/dt max was lowered from 1670 +/- 86 to 1532 +/- 50 mmHg.sec-1 (P < 0.001) and mean blood pressure from 79 +/- 4 to 70 +/- 3 mmHg (P < 0.01) by amlodipine, but dantrolene did not enhance and even counteracted these effects. Finally, potassium plasma concentration did not increase above 5.1 +/- 0.2 mmol.L-1 under the dual influence of amlodipine and dantrolene. CONCLUSION: In usual clinical doses, dantrolene may be safely administered concurrently with amlodipine.

Antihypertensive effect of amlodipine and lack of interference with cyclosporine metabolism in renal transplant recipients.

The catabolism of various calcium channel blockers through cytochrome P-450 is heterogeneous and may be modified by concomitant use of cyclosporin A. In an open study we investigated the antihypertensive effect and clinical tolerance of the dihydropyridine amlodipine and its effects on cyclosporine kinetics in stable hypertensive renal transplant recipients not taking corticosteroids. Ten adult hypertensive patients grafted for 21.4 +/- 8.9 months and well stabilized with normal renal function were included in the study. Renal artery stenosis was ruled out by normal Doppler echography. After 2 weeks of placebo, amlodipine was started at a daily dose of 5 mg. The dose was then adjusted to 10 mg if necessary. Blood and urine chemistries and whole-blood cyclosporine trough levels were measured weekly. Cyclosporine kinetics were determined on a hourly basis before amlodipine administration and after 4 weeks of treatment. Normal blood pressure was obtained with the use of 5 mg/d amlodipine in 7 patients and 10 mg/d in 3, diastolic blood pressure decreasing from 98.7 +/- 3.8 to 81.3 +/- 9.1 mm Hg (P = .0007). Heart rate slightly increased by 10% (P < .02). The drug was well tolerated, and only minor ankle edema was found in 3 patients. Cyclosporine doses were not modified and cyclosporine levels remained unchanged throughout the study. Cyclosporine kinetic parameters were not significantly different at the beginning and end of the study. Bioequivalence was demonstrated indicating that cyclosporine biotransformation was not altered by the concomitant administration of amlodipine.(ABSTRACT TRUNCATED AT 250 WORDS)