RESUMO
OBJECTIVES: To evaluate the patterns of use and perceived benefits and barriers among people living with HIV and their physicians concerning telemedicine and the collection of computerized personal information. METHODS: Multicenter online observational survey from October 15 to 19, 2018. RESULTS: Study participation was accepted by 229 physicians and 838/1,377 PLHIV followed in 46 centers, of which 325 (39%) responded online. We found that while 226/302 (75%) PLHIV accept online prescription renewals and 197/302 (65%) accept online medical certificates, 182/302 (60%) PLHIV-who were more often in material/social deprivation (OR=1.70±0.45; P=0.045), less often born in Île-de-France (OR=0.43±0.15; P=0.018), with lower CD4 T-cell counts (OR=0.999±0.0004; P=0.038), and less often on psychiatric treatment (OR=0.50±0.18; P=0.047)-were receptive to teleconsultations. However, 137/225 (61%) physicians would be uncomfortable teleconsulting due to inadequate data security without it reducing the number of consultations or offering economic benefit. Asked about collection of computerized personal information, 197/296 (67%) PLHIV and 139/223 (62%) physicians agreed it improved quality of care, but 144 (49%) PLHIV and 94/222 (42%) physicians thought it was not sufficiently framed by the law. eHealth was seen as improving coordination between health professionals by 240/296 (81%) PLHIV and seen as a good thing by 181/225 (81%) physicians. CONCLUSION: More than half of PLHIV were ready for telemedicine. PLHIV and physicians endorsed the advantage of e-health in terms of better coordination across health professionals but mistrust the data collection factor, which warrants either clarification or stronger legal protections.
Assuntos
Atitude do Pessoal de Saúde , Atitude Frente a Saúde , Registros Eletrônicos de Saúde , Utilização de Instalações e Serviços/estatística & dados numéricos , Infecções por HIV , Registros de Saúde Pessoal , Médicos , Telemedicina/estatística & dados numéricos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e QuestionáriosRESUMO
OBJECTIVES: To evaluate patterns of use and perceived benefits and barriers to health/wellness applications (apps) and smart devices among people living with HIV (PLHIV) and their physicians. METHODS: Online multicenter observational survey (October 15-19, 2018). RESULTS: Study participation was accepted by 229 physicians and 838/1377 PLHIV followed in 46 centers, of which 325 (39%) responded online. Overall, 83/288 (29%) PLHIV had already downloaded at least one app: these 'downloaders' were younger (OR0.96±0.01, P=0.004), educated to at least university entry level (OR2.27±0.86, P=0.03), and more frequently used geolocation-based dating websites (OR3.00±1.09, P=0.002). However, 227/314 (72%) PLHIV claimed they were ready to use an app recommended by a physician. For the 60/83 PLHIV who answered, the ideal app would be a vaccination tracker (76%) to better communicate with their physician (68%). However, 96/277 (42%) physicians were unable to answer this question and for 94/227 (41%) of them, the ideal patient app would be for schedule management. Although PLHIV used smart devices, 231/306 (75%) would want to report the data to their physicians and 137/225 (61%) of physicians would welcome this exchange. The main physician-side barrier to this exchange was concerns over data security. CONCLUSION: mHealth apps and smart devices have failed to garner adoption by PLHIV. There is a case for good-quality health data sharing and exchange if PLHIV are provided with appropriately secure tools and physicians are backed up by adapted legislation.
Assuntos
Atitude do Pessoal de Saúde , Atitude Frente a Saúde , Utilização de Instalações e Serviços/estatística & dados numéricos , Infecções por HIV , Aplicativos Móveis , Médicos , Smartphone , Telemedicina/estatística & dados numéricos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVES: To identify patterns of use, perceived benefits, and barriers among people living with HIV (PLHIV) of online searches for health information and via social media. METHODS: Online multicentre observational survey (October 15th-19th, 2018). RESULTS: Study participation was accepted by 838/1377 PLHIV followed in 46 centres, of which 325 (39%) responded online: 181 (56%) had already used the Internet to search for health information; 88/181 (49%) on HIV infection and 78 (43%) on nutrition. These 56% were characterised by a higher educational level (OR=1.82±0.50; P=0.028) and more often consulted other specialists (OR=3.14±1.26; P=0.004). A subset of 87/180 (48%) PLHIV had changed the way they looked after their health based on their online research, and were more often in material/social deprivation (P=0.02) and diabetic (P=0.02). A small subset of 19/180 (11%) had already asked or answered a question on a forum; these people tended to be women (P=0.03) in material/social deprivation (P=0.009). 296/322 (92%) PLHIV trusted their physician whereas only 206 (64%) trusted information sourced on medical websites. 238/323 (74%) PLHIV expected their physicians to recommend websites if asked, whereas only 23/323 (7%) had actually been given this guidance. CONCLUSION: More than half of PLHIV surveyed had already searched for health information on the Internet, and one in two had changed their behaviour based on the online search. PLHIV did not see the Internet as an alternative to physicians but they wanted their physicians to guide them on how to find quality health information to better self-manage their condition.
Assuntos
Atitude do Pessoal de Saúde , Atitude Frente a Saúde , Utilização de Instalações e Serviços/estatística & dados numéricos , Infecções por HIV , Armazenamento e Recuperação da Informação , Internet , Médicos , Rede Social , Telemedicina/estatística & dados numéricos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Persistent immune activation is one of the suspected causes of HIV-associated neurocognitive disorders (HAND) in cART era. The CD4/CD8 ratio has been recently showed as a marker of immune activation and HAND. Our aim was to analyze if a decrease in the CD4/CD8 ratio over time could have an impact on neurocognitive deterioration. Randomly selected HIV-infected patients were followed for neuropsychological (NP) testing during a period of almost 2 years. Tests were adjusted for age, gender, and education. Patients were divided into 5 groups: normal tests (NT), neuropsychological deficit (ND, one impaired cognitive domain), asymptomatic neurocognitive disorders (ANI), mild neurocognitive disorders (MND), and HIV-associated dementia (HAD). Risk factors for neurocognitive deterioration were analyzed. Two hundred fifty-six patients underwent NP tests and 94 participated in the follow-up. The groups were comparable. Upon neuropsychological re-testing, six patients showed clinical improvement, 30 had worsened, and 58 were stable, resulting in 42 patients presenting with HAND (45 %). The majority of HAND cases consisted of ANI (26 %) and MND (16 %). In patients whose NP performance worsened, CPE 2010 score was lower at inclusion (7.13 vs 8.00, p = 0.003) and CD4/CD8 decrease more frequent (60 vs 31 %, p = 0.008) than in those who were stable or improved. Multivariate analysis confirmed these results. A decreasing CD4/CD8 ratio during a longitudinal follow-up of randomly selected HIV-infected patients and lower CSF-penetrating regimens were independently associated with cognitive decline. Monitoring trends in CD4/CD8 ratio could contribute to identifying patients at higher risk of neurocognitive deterioration.
Assuntos
Complexo AIDS Demência/imunologia , Antivirais/farmacocinética , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Disfunção Cognitiva/imunologia , HIV/fisiologia , Complexo AIDS Demência/diagnóstico , Complexo AIDS Demência/patologia , Complexo AIDS Demência/virologia , Adulto , Terapia Antirretroviral de Alta Atividade , Antivirais/administração & dosagem , Biomarcadores/análise , Contagem de Linfócito CD4 , Relação CD4-CD8 , Linfócitos T CD4-Positivos/virologia , Linfócitos T CD8-Positivos/virologia , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/patologia , Disfunção Cognitiva/virologia , Feminino , HIV/patogenicidade , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Testes Neuropsicológicos , Permeabilidade , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Replicação ViralRESUMO
To describe the consequences of medical care interruptions (MCIs) we selected patients with at least two medical encounters between January 2006 and June 2013 in the Dat'AIDS cohort. Patients with any time interval >15 months between two visits were defined as having a MCI, as opposed to uninterrupted follow-up (UFU). Patients' characteristics at the time of HIV diagnosis and at the censoring date were compared between groups. Cox proportional hazards models were built to assess the role of interruptions on survival (total and AIDS-free). Of 11 116 patients, 824 had at least one MCI. These patients were younger at the time of HIV diagnosis (30 vs. 33 years, P < 0·0001). MCI was less frequent in men having sex with men vs. heterosexual patients [odds ratio (OR) 0·81, 95% confidence interval (CI) 0·69-0·96)], and a centre effect was described. MCI was independently associated with AIDS (OR 2·54, 95% CI 2·10-3·09) and death (OR 2·65, 95% CI 1·94-3·61). At the censoring date, 52·2% of patients with at least one MCI had viral load below detection vs. 85·3% of the UFU group (P < 0·0001). In conclusion, MCIs were associated with patients' survival and with the proportion of viral loads below detection in our cohort, compromising individual and collective treatment benefits.
Assuntos
Infecções por HIV/prevenção & controle , Cooperação do Paciente/estatística & dados numéricos , Adulto , Estudos de Coortes , Feminino , França , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Modelos de Riscos Proporcionais , Fatores de Risco , Carga Viral , Adulto JovemRESUMO
OBJECTIVES: Inversion of the CD4:CD8 ratio is a marker of immune activation and age-associated disease. We measured the CD4:CD8 ratio as a marker of cognitive impairment in HIV-infected patients and explored differences according to clinical severity. METHODS: Post hoc analysis of data from two prospective cohorts of HIV-infected patients randomly selected to undergo neuropsychological tests was performed. Test scores were adjusted for age, gender and education. Inclusion criteria were undetectable viral load and stable treatment for at least 6 months. Subjects with HIV-associated dementia were excluded. Patients were divided into an unimpaired group, a group with asymptomatic neurocognitive disorder (ANI) and a group with symptomatic HIV-associated neurocognitive disorder (sHAND), represented by mild neurocognitive disorder (MND). Demographic and background parameters, immune activation markers and the CD4:CD8 ratio were recorded. RESULTS: Two hundred patients were included in the study. The mean age was 52 years, 78% were male, the mean CD4 count was 624 cells/µL, the mean nadir CD4 count was 240 cells/µL, 27% were hepatitis C virus (HCV)-coinfected, the mean duration of HIV infection was 16 years, and the mean time on current combination antiretroviral therapy (cART) was 2.9 years. Twenty-nine per cent of subjects had HAND (21% had ANI and 8% had MND). In multivariate analysis, a CD4:CD8 ratio < 1 was associated with a nadir CD4 count < 200 cells/µL [odds ratio (OR) 3.68] and with the presence of CD4(+) CD38(+) HLA(+) cells (OR 1.23). Multinominal logistic regression showed that, in comparison with the unimpaired group, diagnosis of sHAND was associated with a CD4:CD8 ratio < 1 (OR 10.62), longer HIV infection (OR 1.15) and longer current cART (OR 1.34), while the ANI group differed from the unimpaired group only for education level. CONCLUSIONS: Aviraemic patients with sHAND did not display the same pattern of immune activation as subjects with ANI, suggesting that the underlying pathophysiological mechanisms could be different.
Assuntos
Complexo AIDS Demência/imunologia , Transtornos Cognitivos/imunologia , Ativação Linfocitária/imunologia , Complexo AIDS Demência/tratamento farmacológico , Complexo AIDS Demência/fisiopatologia , Relação CD4-CD8 , Transtornos Cognitivos/tratamento farmacológico , Transtornos Cognitivos/fisiopatologia , Estudos Transversais , Feminino , França/epidemiologia , Humanos , Modelos Logísticos , Ativação Linfocitária/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Fatores de Risco , Carga ViralRESUMO
UNLABELLED: Antiretroviral drugs have been available in generic form in developing countries, which has expanded access to treatment; they have also become available in developed countries more recently. OBJECTIVES: The validation of generic drugs (GD) compared to originator drugs (OD) is mandatory to ensure that using generics will lead to a decreased cost of treatment. RESULTS: The results were obtained by analyzing published data as well as European Medicines Agency recommendations. METHOD: The GD should have the same qualitative and quantitative active principle formula, the same pharmaceutical forms, and the same criteria in terms of quality, effectiveness, and safety. This equivalence is based on bioequivalence rules: comparison of the concentration/time curves (AUC); Cmax and Tmax (90%), for which the confidence intervals in the range of 80-125% should be included. Naturally, that does not mean that the concentrations can vary from 80 to 125%: this would indicate unacceptable deviations. Conforming to these criteria allows substituting an OD by a GD. Adverse effects should not be different from those observed for the OD. Adverse effects observed when the GD is used must be notified, as is the case for the OD. Accountability is established according to 4 essential pieces of information: a prescriber, a patient, a drug, and an adverse effect. It is sometimes difficult to identify the provider of the GD that has been delivered. CONCLUSION: The level of safety concerning effectiveness and tolerance required is identical for OD and GD, in Europe. Analyzing confirmed adverse effects and therapeutic failures is the only way to identify differences that could question a GD's effectiveness.
Assuntos
Antirretrovirais/farmacocinética , Medicamentos Genéricos/farmacocinética , Farmacovigilância , Equivalência Terapêutica , HumanosRESUMO
OBJECTIVE: The authors had for objective to describe HIV-infected patients treated with ABC (Ziagen(®), ABC), and the immune, virological, and clinical treatment outcome between 2003 and 2008. PATIENTS AND METHODS: We performed a retrospective analysis of the Dat'AIDS database on patients who were treated with ABC for the first time between 2003 and 2008. RESULTS: Eight hundred and thirty-six patients were included. Before initiation of ABC, 26.3% has stopped the previous treatment because of immuno-virological failure, 30.5% because of adverse events, and 29.8% for other reasons. Thirteen percent were antiretroviral naive. One third of patients were ranked as CDC class C, and more than 2/3 had a viral load<5 log copies/mL or a CD4 count≥200mm(3). ABC was mainly included in a combination containing 2 NRTI and 1 PI (63%), or 1 non-NRTI (16%). Thirty-two percent of patients were still treated with ABC after 2years of treatment and the median of ABC treatment was 11months (IQ 84days-2years). The main causes for stopping ABC were therapeutic simplification (47.4% of patients), intolerance (19.0%), and immuno-virological failure (9.8%). Suspected hypersensitivity reactions were the main cause of discontinuation due to intolerance (27.6%); the rate was 3.8% when ABC had been introduced before the routine use of the screening test HLA-B*5701. The incidence of myocardial infarction was 3.8 per 1000 patient-years; 70.6% of patients received a fixed combination including ABC after discontinuation of ABC as a single agent (Ziagen(®)). CONCLUSION: This retrospective analysis confirmed the effectiveness and the good tolerance of ABC in the therapeutic strategy, between 2003 and 2008.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Didesoxinucleosídeos/uso terapêutico , Registros Eletrônicos de Saúde/estatística & dados numéricos , Inibidores da Transcriptase Reversa/uso terapêutico , Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Adulto , Fármacos Anti-HIV/efeitos adversos , Terapia Antirretroviral de Alta Atividade , Contagem de Linfócito CD4 , Didesoxinucleosídeos/efeitos adversos , Hipersensibilidade a Drogas/etiologia , Hipersensibilidade a Drogas/imunologia , Quimioterapia Combinada , Uso de Medicamentos/estatística & dados numéricos , Feminino , França , Predisposição Genética para Doença , Infecções por HIV/tratamento farmacológico , HIV-1/efeitos dos fármacos , HIV-1/genética , HIV-1/isolamento & purificação , Antígenos HLA-B/análise , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/induzido quimicamente , Estudos Retrospectivos , Inibidores da Transcriptase Reversa/efeitos adversos , Resultado do Tratamento , Carga Viral , Viremia/tratamento farmacológicoRESUMO
To estimate the cost of the first combination antiretroviral drug therapy (cART) in HIV-infected patients and to determine factors associated with expensive prescriptions, 1698 patients starting cART between September 2002 and September 2007 were selected from the Dat'AIDS cohort. A multivariate linear regression model was used to assess associations between the cost of first cART and patient characteristics, clinical centre and cART adequacy. At cART initiation, the median age was 39 years, median CD4 count was 223 cells/mm(3), median viral load (VL) was 5.2 log copies/mL and 18.3% presented with AIDS. cART was concordant with the French guidelines in 88.7%. The mean cost of cART varied from 26.69/day/person in 2002-2003 to 32.23 in 2006-2007 (P < 0.0001), cost was associated with previous AIDS diagnosis (31.83/day/person) versus (29.49; P < 0.0001), baseline VL > 5 log copies/mL (30.99/day/person) versus (28.33; P < 0.0001) and centre. cART regimen not concordant with guidelines were more expensive (38.31/day/person) versus (29.07; P < 0.0001). After adjusting for the year of initiation, the previous AIDS diagnosis, VL and recommended cART regimen, differences were still found between centres (from 27.81/day/person) to (33.12; P < 0.0001). Cost should be considered when choosing a first cART regimen, especially when considering clinically equivalent regimens.
Assuntos
Antirretrovirais/economia , Infecções por HIV/economia , Adulto , Antirretrovirais/uso terapêutico , Custos de Medicamentos , Prescrições de Medicamentos/economia , Quimioterapia Combinada/economia , Quimioterapia Combinada/métodos , Feminino , França , Infecções por HIV/tratamento farmacológico , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
Tenofovir (TDF), atazanovir (ATAZ) and indinavir (IND) have been reported as possible risk factors for incident chronic kidney disease (CKD) in HIV-infected patients. We investigated the relationship between the duration of antiretroviral exposure and estimated glomerular filtration rate (eGFR) evolution in CKD patients. In a cohort of 1,750 HIV-infected patients, we identified 121 CKD patients with a mean follow-up of 44 ± 35 months. The relationship between mean eGFR at baseline, eGFR slope and time exposure to antiretroviral treatment as well as confounding factors were investigated using a joint modeling procedure. Seventy (58%), 30 (25%) and 33 patients (27%), with a mean age of 50.3 ± 11.7 years, mean eGFR at baseline of 53.0 ± 0.8 (ml/min/1.73 m(2)) and eGFR slope of 0.46 ± 0.07 ml/min/1.73 m(2)/year, were exposed to TDF, ATAZ and IND, respectively. In univariate analysis, hepatitis C virus infection, decreased nadir of log CD4 count, high blood pressure at baseline, angiotensin-converting enzyme inhibitor treatment and greater time exposure to TDF during follow-up were associated with a higher slope, whereas greater time exposure to IND was associated with a lower slope. In multivariate analysis, higher TDF time exposure was still significantly associated with eGFR decline, with a dose-effect relationship (slope ± standard error of the mean: 1.1 ± 0.1, 0.5 ± 0.1, -0.07 ± 0.08 and -0.87 ± 0.06 ml/min/1.73 m(2)/year for no time exposure, <34, 34-67 and ≥67%, respectively; trend test: p < 0.001), whereas the IND time exposure association was abolished. In HIV patients with CKD, a greater TDF time exposure was independently associated, in a graded manner, with a greater eGFR decline.
Assuntos
Adenina/análogos & derivados , Fármacos Anti-HIV/administração & dosagem , Taxa de Filtração Glomerular/efeitos dos fármacos , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Falência Renal Crônica/etiologia , Organofosfonatos/administração & dosagem , Adenina/administração & dosagem , Feminino , Humanos , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Tenofovir , Fatores de TempoRESUMO
One of the choice criteria for antiretroviral therapy, once the viral load is controlled, is long-term treatment safety. Safety, despite similarities in each therapeutic class, can differ significantly from one agent to another, according to their respective pharmacokinetic and pharmacodynamic properties. We reviewed data on two very well-known NNRTIs, efavirenz and nevirapine, in this context. The pharmacokinetic properties of both agents are presented along with their impact on residual viremia and viral reservoirs, as well as their clinical consequences. The implications for the penetration of these antiretroviral drugs in the CNS and in female and male genital tracts are also discussed. Pharmacogenetics could become an interesting tool. Finally, the availability of new NNRTIs has recently boosted this therapeutic class, even if their long-term properties remain to be assessed. The consideration of all this data stresses the importance of communication among clinicians, virologists, and pharmacologists before choosing a treatment.
Assuntos
Infecções por HIV/tratamento farmacológico , Inibidores da Transcriptase Reversa/uso terapêutico , Feminino , Humanos , Masculino , Inibidores da Transcriptase Reversa/farmacocinética , Inibidores da Transcriptase Reversa/farmacologiaRESUMO
The contribution of efavirenz and nevirapine remains clinically relevant and is the reason for the frequent prescription of these two agents. Recent clinical data on efavirenz and nevirapine in naive patients confirms their effectiveness compared to protease inhibitors such as lopinavir/r (ACTG 5142) or atazanavir/r (ACTG 5202) for efavirenz, or such as atazanavir/r (ARTEN trial) for nevirapine. Their easy use is another advantage; efavirenz is part of the first triple therapy as a single tablet given once a day, and nevirapine, with its new extended-release formulation, was designed for a single daily intake. However, the two agents exhibit different safety profiles and pharmacological properties. Their penetration rates in the genital tracts are different (70 to 80% for nevirapine versus 0 to 3% for efavirenz in men and 13-80% for nevirapine versus 0 to 4% for efavirenz in women). Finally, the authors of two recent studies reported the differences in the residual VL measured by ultrasensitive assays in successfully treated patients. The VL of patients treated with nevirapine was significantly more frequently below the detection limit of 1 or 2.5 RNA copies/mL than patients treated with efavirenz.
Assuntos
Infecções por HIV/tratamento farmacológico , Inibidores da Transcriptase Reversa/uso terapêutico , Alcinos , Benzoxazinas/uso terapêutico , Ciclopropanos , Previsões , Humanos , Nevirapina/uso terapêuticoRESUMO
OBJECTIVES: We wanted to assess the quality of antibiotic therapy prescribed for infective endocarditis in our ward. DESIGN: We conducted a retrospective audit of all adult patients with endocarditis hospitalized over a 3-year period in the Infectious Diseases Unit of the Nice University Hospital, France. The quality of antibiotic therapy was assessed using the 2004 European Society of Cardiology guidelines as a reference. Antibiotic therapy was considered as appropriate only if the five following items complied with guidelines: antibiotic, dose, route, interval of administration, and duration of antibiotic treatment. RESULTS: Sixty-six patients were included, 63years of age on average. Antibiotic therapy complied with guidelines in 14% of the cases. The most frequent causes of inappropriate therapy were: gentamicin prescribed as a single daily dose in 55% (27/49) of the cases, unnecessary prescriptions of rifampin in 72% (18/25) of the cases, and too long duration of gentamicin course for staphylococcal endocarditis in 32% (9/28) of the cases. Antibiotic therapy was switched from intravenous to oral route in 29% of the patients (n=19), 18±9 days after starting therapy on average. These endocarditis were mainly left-sided (n=12) and/or complicated (n=15). There was no significant association between mortality and inappropriate antibiotic therapy (14% if inappropriate vs. 22%, P=0.62) or between mortality and oral switch (0% if oral switch vs. 21%, P=0.052). CONCLUSIONS: Infective endocarditis antibiotic treatment rarely complied with the 2004 European guidelines, but this did not have a negative impact on mortality. Switching antibiotic therapy from intravenous to oral route was common, even for complicated left-sided endocarditis, and was associated with a favorable outcome in all cases.
Assuntos
Antibacterianos/uso terapêutico , Endocardite Bacteriana/tratamento farmacológico , Administração Oral , Adulto , Idoso , Antibacterianos/administração & dosagem , Comorbidade , Uso de Medicamentos/estatística & dados numéricos , Endocardite Bacteriana/epidemiologia , Feminino , França/epidemiologia , Fidelidade a Diretrizes , Unidades Hospitalares , Hospitais Universitários/estatística & dados numéricos , Humanos , Prescrição Inadequada , Infectologia/organização & administração , Infusões Intravenosas , Masculino , Auditoria Médica , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto , Estudos Retrospectivos , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/epidemiologia , Infecções Estreptocócicas/tratamento farmacológico , Infecções Estreptocócicas/epidemiologia , Resultado do TratamentoRESUMO
UNLABELLED: Modalities of bone infection therapeutic follow-up are controversial, notably for biological and radiological parameters. We have proposed six weeks of antibiotic therapy for all patients presenting with bone infection, since July 2005. Therefore, biological and radiological exams performed during the treatment were not taken into account when determining the duration of antibiotherapy. This protocol allows determining the usefulness of these biological and radiological parameters. METHODS: All patients presenting with bone infection, from July 2005 to July 2008, were included. Inflammatory biological parameters such as C-reactive protein (CRP) and sedimentation rate were analyzed, and values were considered as normal when less than 10 mg/L and less than 15 mm respectively. All available CT- and MR imaging were analyzed by the same referent radiologist. RESULTS: Eighty-seven patients presenting with bone infection received antibiotic therapy for a mean [SD] 42 ± 0.3 days. Cure was reported in 82 patients (94%) with a mean follow-up after antibiotic therapy of 36 ± 9 months, five patients relapsed. CRP was available in 66 cases by the end of antibiotic therapy, it was normal in 40/64 of patients with favorable outcome (62%) and in one case of unfavorable outcome. The sedimentation rate was available in 22 cases, and normal in seven cases of favorable outcome (32%). By the end of antibiotic therapy, CT-scan showed active bone infection for 15/23 of patients with favorable outcome (65%), while MR imaging suggested the same diagnosis in 8/14 cases (57%). CONCLUSION: Biological parameters and radiological findings are inadequate to determine the duration of antibiotic therapy in bone infection.
Assuntos
Antibacterianos/administração & dosagem , Infecções Relacionadas à Prótese/tratamento farmacológico , Proteína C-Reativa/análise , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infecções Relacionadas à Prótese/sangue , Infecções Relacionadas à Prótese/diagnóstico por imagem , Radiografia , Estudos Retrospectivos , Fatores de TempoRESUMO
This study evaluated the effects of single-dose administration and steady-state concentrations of tipranavir 500 mg and ritonavir 200 mg (TPV/r) combination on the pharmacokinetics of tadalafil 10 mg (TAD) in an open-label study. Seventeen healthy male volunteers received sequential dosing of the studied product: TAD (day 1) alone in a single dose for 7 days followed by TAD (day 8) in a single dose with TPV/r (500/200 mg twice daily, days 8-18). Pharmacokinetic parameters were determined in a noncompartmental analysis. The geometric mean ratio and 90% confidence interval were used to evaluate drug interactions. The effect of a single dose of TAD on the pharmacokinetics of TPV/r resulted in a small decrease in exposure after either first-dose or steady-state TPV/r (geometric mean ratios [90% confidence interval]: area under the concentration-time curve, 0.85 [0.74-0.97]). In contrast, coadministration of TAD exposure was increased significantly (2.33 [2.02-2.69]) when administered with the first dose of TPV/r but not when TPV/r steady state was reached (1.01 [0.83-1.21]). Antiretroviral activity may not be reduced, but the dose of TAD should be reduced at the start of TPV/r therapy and then a full dose can be resumed after steady state is reached.
Assuntos
Carbolinas/farmacocinética , Inibidores da Protease de HIV/farmacocinética , Inibidores da Fosfodiesterase 5/farmacocinética , Piridinas/farmacocinética , Pironas/farmacocinética , Ritonavir/farmacologia , Adulto , Disponibilidade Biológica , Carbolinas/efeitos adversos , Carbolinas/sangue , Estudos Cross-Over , Interações Medicamentosas , Inibidores da Protease de HIV/efeitos adversos , Inibidores da Protease de HIV/sangue , Meia-Vida , Humanos , Masculino , Taxa de Depuração Metabólica , Inibidores da Fosfodiesterase 5/efeitos adversos , Inibidores da Fosfodiesterase 5/sangue , Piridinas/efeitos adversos , Piridinas/sangue , Pironas/efeitos adversos , Pironas/sangue , Ritonavir/efeitos adversos , Sulfonamidas , Tadalafila , Adulto JovemRESUMO
BACKGROUND: It has been suggested that patients who initiate highly active antiretroviral therapy (HAART) late in their course of infection may have suboptimal CD4 T-cell gains, persistent alterations in T-cell subsets and residual inflammation. To address this issue, we carried out a comprehensive 48-week immunological study in HIV-infected patients who had experienced failures of prior therapies, had low CD4 cell counts, and were receiving enfuvirtide-based salvage therapy. METHODS: Immunological monitoring of peripheral lymphocytes from enfuvirtide-responder patients was performed over a 48-week period. A detailed assessment of immune cell subsets, their activation state [CD38 and human leucocyte antigen (HLA)-DR expression] and homeostasis [activation-induced cell death (AICD) and Ki67 expression], and the expression of co-receptors was performed by flow cytometry. Cytokine and chemokine signatures were assessed using multianalyte profiling technology. RESULTS: Enfuvirtide-based salvage therapy induced a progressive restoration of naïve and central memory CD4 T cells, associated with a decrease in their activation state, suppression of premature priming for AICD and increased expression of Ki67. In addition, a significant decrease in C-C chemokine receptor 5 (CCR5) expression was detected on CD4 T cells, which was strongly correlated with the suppression of immune activation. Changes in circulating proinflammatory molecules occurred; i.e. there were decreases in the concentrations of interleukin (IL)-12, macrophage inflammatory protein MIP-1α, MIP-1ß, monokine induced by IFNγ (MIG) and interferon-γ-inducible protein-10 (IP-10). The decline in circulating IL-12 and IP-10 was correlated with both the reduction in the viral load and CD4 T-cell restoration. CONCLUSIONS: This study shows that suppression of HIV-1 replication with enfuvirtide-based salvage therapy in patients with low CD4 cell counts may result in an immunological benefit, characterized by the restoration of CD4 T-cell subsets associated with decreased immune activation and suppression of inflammation.
Assuntos
Linfócitos T CD4-Positivos/imunologia , Quimiocina CXCL10/sangue , Proteína gp41 do Envelope de HIV/uso terapêutico , Inibidores da Fusão de HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Interleucina-12/sangue , Fragmentos de Peptídeos/uso terapêutico , Receptores CCR5/metabolismo , Adolescente , Adulto , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Linfócitos T CD4-Positivos/efeitos dos fármacos , Enfuvirtida , HIV-1/efeitos dos fármacos , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Terapia de Salvação , Carga Viral , Replicação Viral/efeitos dos fármacos , Adulto JovemRESUMO
OBJECTIVE: To evaluate the therapeutic utility of the viral load (VL) measurement after one month (M1) of antiretroviral (ARV) treatment. PATIENTS AND METHOD: A retrospective study of HIV patients included in the NADIS database from 1998 to 2006 and followed at Nice University Hospital. We included ARV-naive patients who received ARV (3-drug combination) for at least 3 months and ARV-experienced patients beginning a new ARV after virologic failure. RESULTS: The NADIS database included 1065 patients from 1998 to 2006. We included 262. In all, 234 of them had VL measured at M1 and are considered in this analysis. Their mean age was 44 years, and 174 were men, for a sex ratio of 9.1. ARV-naïve patients accounted for 35% of the sample (n = 81) and previously treated patients 65% (n = 153). All the naive patients had a VL decrease at M1 > 1 log, as did all but 14 of the previously treated patients (9%). This virological result was followed by a medical action 21 times for the naive patients and 97 times for the previously treated patients (p < 0.004). CONCLUSION: The VL measurement at M1 indicates a virological objective that was reached for all the naive patients and 91% of the previously treated patients. Moreover, the medical actions taken at M1 for a new ARV treatment appear to be associated with the patient's treatment history and not the virological results.
Assuntos
Antirretrovirais/uso terapêutico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Carga Viral , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo , Adulto JovemRESUMO
OBJECTIVE: The study's objective was to assess General Practitioners' (GPs) perceptions of their antibiotic prescribing practice and of bacterial resistance. DESIGN: We surveyed a random sample of 102 GPs out of the 1242 working in the Alpes-Maritimes area (France). RESULTS: The response rate was 69%. More than 80% of the GPs felt confident when prescribing an antibiotic. The two main factors thought to influence their antibiotic prescriptions were their previous experience (97%) and guidelines (81%), advice from a colleague was quoted by only 13% of the GPs. Antibiotic resistance was perceived as a national problem by 91% of the respondents, but only 65% rated the problem as important in their own daily practice. Widespread and inappropriate antibiotic use, prescription of broad spectrum antibiotics or too low antibiotic doses were rated as important causes of resistance, but excessive duration of antibiotic treatment or poor hand hygiene practices were cited less often. The three measures perceived to be helpful or very helpful to improve antibiotic prescribing by more than 80% of the GPs were training sessions, availability of guidelines and of resistance data. CONCLUSIONS: These perceptions must be taken into account to maximize adherence of GPs to the measures intended to limit bacterial resistance.
Assuntos
Resistência Microbiana a Medicamentos , Clínicos Gerais/psicologia , Conhecimentos, Atitudes e Prática em Saúde , Padrões de Prática Médica , Uso de Medicamentos , Educação Médica Continuada , França , Clínicos Gerais/educação , Clínicos Gerais/estatística & dados numéricos , Desinfecção das Mãos , Humanos , Guias de Prática Clínica como Assunto , Estudos de Amostragem , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: Post-exposure prophylaxis (PEP) is recommended for the management of sexual HIV-risk exposure. However, a high percentage of exposed patients discontinue both their 28-day prophylaxis course before 15 days and HIV testing follow-up before M3. The objective of this study is to assess the efficacy of a counseling intervention in enhancing both adherence to PEP and HIV testing follow-up. METHODS: Between 1 June 2004 and 31 December 2005, 54 patients exposed to sexual HIV-risk exposure were included in a multicenter, prospective, controlled, randomized trial, comparing a group receiving a counseling intervention in addition to traditional medical management (intervention group (IG), n=28) vs. a control group (CG, n=26). Patients in the IG received interactive counseling interventions focused on adherence to PEP and to HIV testing follow-up, led by specially trained nurses. The main outcome measures were proportion of patients achieving 100% adherence to PEP as evaluated on D15 by a self-completed patient questionnaire and on HIV testing on D45 and M3. RESULTS: Groups were well balanced at baseline for age, sex, and circumstances of exposure. The proportion of 100% adherent patients to PEP was significantly higher in the IG compared to the CG (54% vs. 23%, p=0.036). Patients in the IG were more likely to complete the HIV testing follow-up at D45 (86% vs. 54%, p=0.023) and M3 (68% vs. 38%, p=0.056). CONCLUSIONS: This study suggests the effectiveness of a counseling program to enhance adherence to both PEP and HIV testing follow-up after sexual exposure.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Aconselhamento/métodos , Infecções por HIV/tratamento farmacológico , Cooperação do Paciente , Profilaxia Pós-Exposição/métodos , Comportamento Sexual/psicologia , Adulto , Feminino , França , Infecções por HIV/prevenção & controle , Infecções por HIV/psicologia , Humanos , Masculino , Estudos Prospectivos , Fatores de Risco , Resultado do TratamentoRESUMO
BACKGROUND: The toxicities, cost and complexity of triple combinations warrant the search for other treatment options, such as boosted protease inhibitor (PI) monotherapy. MONotherapy AntiRetroviral Kaletra (MONARK) is the first randomized trial comparing lopinavir/ritonavir monotherapy to triple combination therapy with zidovudine/lamivudine and lopinavir/ritonavir in antiretroviral-naïve patients. METHODS: A total of 136 antiretroviral-naïve patients, with a CD4 cell count above 100 cells/microL and a plasma HIV RNA below 100,000 HIV-1 RNA copies/mL, were randomized and dosed with either lopinavir/ritonavir monotherapy (n = 83) or lopinavir/ritonavir + zidovudine/lamivudine (n = 53). We focus here on patients in the lopinavir/ritonavir monotherapy arm followed to week 96. The intent-to-treat (ITT) analysis initially involved all patients randomized to lopinavir/ritonavir monotherapy (n = 83), and then focused on patients who had an HIV RNA < 50 copies/mL at week 48 (n = 56). RESULTS: At week 96, 39 of 83 patients (47%) had HIV RNA < 50 copies/mL, five of 83 had HIV RNA between 50 and 400 copies/mL, and three of 83 had HIV RNA > 400 copies/mL. Focusing on the 56 patients with an HIV RNA < 50 copies/mL at week 48, 38 of 56 patients (68%) had a sustained HIV RNA < 50 copies/mL to week 96. To week 96, a total of 28 patients (34%) had discontinued the study treatment. In addition, the allocated treatment was changed for seven patients. PI-associated resistance mutations were evident in five of 83 patients in the monotherapy arm from baseline to week 96. CONCLUSION: By ITT analysis, 39 of the 83 patients initially randomized to lopinavir/ritonavir monotherapy had HIV RNA < 50 copies/mL at week 96. The occurrence in some patients of low-level viraemia (50-500 copies/mL) may increase the risk of drug resistance. First-line lopinavir/ritonavir monotherapy cannot be systematically recommended.