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1.
BMC Health Serv Res ; 22(1): 567, 2022 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-35477443

RESUMO

BACKGROUND: In a context where the economic burden of HIV is increasing as HIV patients now have a close to normal lifespan, the availability of generic antiretrovirals commonly prescribed in 2017 and the imminence of patent expiration are expected to provide substantial savings in the coming years. This article aims to assess the economic impact of these generic antiretrovirals in France and specifically over a five-year period. METHODS: An agent-based model was developed to simulate patient trajectories and treatment use over a five-year period. By comparing the results of costs for trajectories simulated under different predefined scenarios, a budget impact model can be created and sensitivity analyses performed on several parameters of importance. RESULTS: The potential economic savings from 2019 to 2023 generated by generic antiretrovirals range from €309 million when the penetration rate of generics is set at 10% to €1.5 billion at 70%. These savings range from €984 million to €993 million as the delay between patent and generic marketing authorisation varies from 10 to 15 years, and from €965 million to €993 million as the Negotiated Price per Unit (NPU) of generics at market-entry varies from 40 to 50% of the NPU for patents. DISCUSSION: This economic savings simulation could help decision makers to anticipate resource allocations for further innovation in antiretrovirals therapies as well as prevention, especially by funding the Pre-Exposure Prophylaxis (PrEP) or HIV screening.


Assuntos
Infecções por HIV , Antirretrovirais/uso terapêutico , Custos de Medicamentos , Medicamentos Genéricos/uso terapêutico , França , Infecções por HIV/tratamento farmacológico , Humanos
2.
Eur J Clin Microbiol Infect Dis ; 40(6): 1329-1331, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33432493

RESUMO

Corynebacteria are rare causative agents of infective endocarditis. This is a reported case of a destructive aorto-mitral infective endocarditis caused by Arthrobacter woluwensis. Microbial identification was achieved by 16S rRNA polymerase chain reaction on valve tissue samples. Outcome was favorable after surgical valve replacement and 4-week antibiotic treatment.


Assuntos
Arthrobacter/isolamento & purificação , Endocardite Bacteriana/microbiologia , Antibacterianos/uso terapêutico , Arthrobacter/efeitos dos fármacos , Arthrobacter/genética , Endocardite Bacteriana/diagnóstico , Endocardite Bacteriana/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade
3.
J Antimicrob Chemother ; 72(1): 240-245, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27629069

RESUMO

OBJECTIVES: We assessed factors, including treatment course, associated with failure to obtain a 10 year immunological response after starting first-generation PI-containing combined ART (cART). PATIENTS AND METHODS: In the prospective COPILOTE cohort of HIV-infected patients started on a first-generation PI-containing regimen in 1997-99, the impact of cART history on the failure to achieve immunological response measured at 10 years was assessed by multivariate logistic regression models in the 399 patients with clinical and virological success of cART. RESULTS: Failure of CD4 response (CD4 >500/mm3) was associated with age ≥40 years at baseline (P < 0.001), CD4 cell counts ≤500/mm3 at month 4 (P = 0.016) or month 12 (P < 0.001) and ≥3 months of cART interruption (P = 0.016). Factors associated with failure to achieve complete immunological response (CD4 >500/mm3 and CD4:CD8 ratio >1) were CD4:CD8 ratio ≤0.8 at month 8 (P < 0.001) or month 12 (P < 0.001), ≥3 months of cumulative cART interruption (P = 0.011), ≥3 antiretroviral regimens (P = 0.009) and ≤4 treatment lines (P = 0.015). Baseline CD4 and CD4:CD8 ratio were not predictors of the 10 year immunological outcomes. CONCLUSIONS: In this therapeutic cohort of patients starting first-generation PI-containing cART in 1997-99, poor initial immunological response had a negative impact on 10 year CD4 and CD4 plus CD4:CD8 ratio response, despite prolonged virological success. Lack of treatment interruption may improve long-term immunological outcome in HIV infection.


Assuntos
Antirretrovirais/uso terapêutico , Terapia Antirretroviral de Alta Atividade/métodos , Infecções por HIV/tratamento farmacológico , Adulto , Contagem de Linfócito CD4 , Relação CD4-CD8 , Feminino , Infecções por HIV/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Falha de Tratamento
4.
J Antimicrob Chemother ; 71(11): 3235-3241, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27432606

RESUMO

OBJECTIVE: We assessed the virological efficacy of a 6 month maraviroc/raltegravir simplification strategy following 6 months of quadruple therapy combining tenofovir disoproxil fumarate/emtricitabine with maraviroc/raltegravir. METHODS: HIV-1-infected naive patients were enrolled in an open label, single-arm, Phase 2 trial. All patients received maraviroc 300 mg twice daily, raltegravir 400 mg twice daily and tenofovir/emtricitabine for 24 weeks. Patients with stable HIV-RNA <50 copies/mL stopped tenofovir/emtricitabine at week (W) 24 and pursued maraviroc/raltegravir until W48. The primary endpoint was the virological response defined by HIV-RNA <50 copies/mL at W48. RESULTS: Thirty-three patients were analysed. Patients were mostly male (94%), Caucasians (91%), MSM (82%); their median age was 42 years. At baseline, median CD4 cell count was 453 cells/mm3 and HIV-RNA was 4.3 log copies/mL. All patients had CCR5-tropic viruses by genotropism and phenotropism assays. All but one patient had an HIV-RNA < 50 copies/mL at W24 and entered the simplification phase. Virological success was maintained at W48 in 88% (90% CI 79%-97%) of patients. N155H mutation was detected at failure in one patient. No tropism switch was observed. Raltegravir and maraviroc plasma exposure were satisfactory in 92% and 79% of 41 samples from 21 patients. Five severe adverse events (SAEs) were observed up to W48; none was related to the study drugs. Four patients presented grade 3 AEs; none was related to the study. No grade 4 AE was observed. No patient died. CONCLUSIONS: Maraviroc/raltegravir maintenance therapy following a 6 month induction phase with maraviroc/raltegravir/tenofovir/emtricitabine was well tolerated and maintained virological efficacy in these carefully selected patients.


Assuntos
Fármacos Anti-HIV/administração & dosagem , Terapia Antirretroviral de Alta Atividade/métodos , Cicloexanos/administração & dosagem , Infecções por HIV/tratamento farmacológico , Quimioterapia de Manutenção/métodos , Raltegravir Potássico/administração & dosagem , Triazóis/administração & dosagem , Adolescente , Adulto , Fármacos Anti-HIV/efeitos adversos , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Cicloexanos/efeitos adversos , Emtricitabina/administração & dosagem , Feminino , HIV-1/isolamento & purificação , Humanos , Quimioterapia de Manutenção/efeitos adversos , Masculino , Maraviroc , Pessoa de Meia-Idade , Raltegravir Potássico/efeitos adversos , Tenofovir/administração & dosagem , Resultado do Tratamento , Triazóis/efeitos adversos , Carga Viral , Adulto Jovem
5.
J Neurovirol ; 19(4): 376-82, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23846287

RESUMO

Contributory factors to HIV-associated neurocognitive disorders (HAND) have been shown to include age, co-morbid infections, medication toxicity, virological, genetic and vascular mechanisms, as well as microbial translocation of lipopolysaccharide (LPS), which is suspected to trigger monocyte activation and increase trafficking of infected cells into the brain. In this study, our aim was to assess the degree of neurocognitive impairment in a group of randomly selected HIV-infected patients and investigate potential risk factors, including LPS plasma levels. Furthermore, we evaluated the relevance of LPS as a potential marker for screening patients with mild neurocognitive impairment. LPS plasma levels were compared among patients with HAND and those with no HAND. As LPS has also been shown to be elevated in hepatitis C co-infection, the analysis was stratified according to the presence or not of hepatitis C virus (HCV) co-infection. Differences between groups were evaluated using chi-square tests and Kruskal-Wallis non-parametric tests. Stepwise logistic regression was performed to identify independent risk factors for HAND in the subgroups of HCV-positive and negative patients. A p value <0.05 was considered significant. Analyses were conducted using SPSS® software. From December 2007 to July 2009, 179 patients were tested (mean age 44, 73 % male, 87 % on treatment, 30 % HCV co-infected, median CD4 504/ml and 67 % with viral load below 40 copies/ml). HAND was identified in 40/179 patients (22 %), the majority displaying asymptomatic neurocognitive impairment or mild neurocognitive disorder. Univariate analysis showed that age, illicit drug use, hepatitis C co-infection, prior AIDS-defining events, CD4/CD8 ratio and LPS plasma levels were significantly associated with HAND. The median LPS level was 98.2 pg/ml in the non-HAND group versus 116.1 pg/ml in the HAND group (p < 0.014). No differences were found in LPS values between subgroups of impairment. There was a clear association between LPS levels and HAND in the HCV-positive group (p = 0.036), while there was none in the HCV-negative group (p = 0.502). No difference in degree of hepatic fibrosis was found between the HAND and non-HAND groups. In conclusion, LPS levels were associated with HAND in the HCV-positive group, while, in the HCV-negative group, age and pro-viral DNA were the only variables independently associated with HAND. There was no difference in degree of liver disease as predicted by score of fibrosis between HAND and non-HAND groups. The role of HCV co-infection and higher LPS levels in the pathogenesis of HAND in patients with viral suppression on treatment requires further investigation.


Assuntos
Complexo AIDS Demência/sangue , Infecções por HIV/sangue , Infecções por HIV/complicações , Hepatite C/complicações , Lipopolissacarídeos/sangue , Adulto , Coinfecção , Feminino , Hepatite C/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos
6.
Virol J ; 9: 174, 2012 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-22925532

RESUMO

BACKGROUND: Recent observational studies suggest a role for lipopolysaccharide (LPS) as a marker of immune activation in HIV-infected patients, with potential repercussions on the effectiveness of antiretroviral regimens. OBJECT: A systematic review of LPS as a marker of immune activation in HIV-1 infected patients. DATA SOURCES: MEDLINE register of articles and international conference proceedings. REVIEW METHODS: Case-control studies comparing the role of plasma LPS as a marker of immune activation in HIV-infected patients versus HIV negative subjects. DATA SYNTHESIS: Two hundred and six articles were selected using MEDLINE, plus 51 studies presented at international conferences. Plasma LPS is a marker of immune activation in HIV-infected patients, determining the entry of central memory CD4+ T cells into the replication cycle and finally generating cell death. Plasma LPS probably results from immune-mediated alterations of the intestinal barrier, which can occur soon after HIV seroconversion. LPS is a likely marker of disease progression, as it drives chronic monocyte activation, and some studies suggest that hyperexpression of CCR5 receptors, related to LPS plasma levels, could be responsible for monocyte trafficking in the brain compartment and for the appearance of HIV-associated neurocognitive disorders. Long-term combination antiretroviral therapy (cART) generally reduces LPS concentrations, but rarely to the same levels as in the control group. This phenomenon probably depends on ongoing but incomplete repair of the mucosal barrier. Only in patients achieving maximal viral suppression (i.e. viral load < 2.5 cp/ml) are LPS levels comparable to healthy donors. In successfully treated patients who did not restore CD4+ T cells, one hypothesis is that the degree of residual microbial translocation, measured by LPS, alters the turnover of CD4+ T cells. CONCLUSIONS: LPS is a marker of microbial translocation, responsible for chronic immune activation in HIV-infected patients. Even in successfully treated patients, LPS values are rarely normal. Several studies suggest a role for LPS as a negative predictive marker of immune restoration in patients with blunted CD4 T cell gain.


Assuntos
Translocação Bacteriana/imunologia , Infecções por HIV/imunologia , Infecções por HIV/patologia , Lipopolissacarídeos/sangue , Lipopolissacarídeos/imunologia , Estudos de Casos e Controles , Infecções por HIV/complicações , Humanos , Plasma/química
7.
Scand J Infect Dis ; 44(1): 37-43, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21851330

RESUMO

BACKGROUND: In highly antiretroviral-experienced patients with a multidrug-resistant human immunodeficiency virus (HIV) infection, recommended regimens should preferentially contain 3 active components, including a ritonavir-boosted protease inhibitor (PI/r). Tipranavir/r (TPV/r), a non-peptidic PI, has been specifically developed for patients resistant to the usual antiretroviral classes including PIs. This paper discusses the role of TPV/r in patients experiencing multiple PI resistance. METHODS: Virological, immunological, and safety outcomes were collected between 2003 and 2007 at 7 clinical units. Virus resistance assessment was based on 3 different genotypic tests. The 207 patients evaluated had previously received nucleoside reverse transcriptase inhibitors (NRTIs) and PIs. RESULTS: The main drugs co-administered with TPV/r were 1 or 2 NRTIs associated, in half of the patients, with enfuvirtide. After 12 weeks, viral load was <50 copies/ml in 38% of the patients (44% with enfuvirtide), while median CD4 counts had increased from 150 to 250 cells/mm³. Genotypic testing suggested that most of the patients had viruses susceptible to TPV. Lipid and transaminase levels were slightly modified, and less than 10% of treatment discontinuations were due to gastrointestinal events. CONCLUSION: A regimen including TPV/r associated with at least 1 active component is a valuable option in highly ARV-experienced patients with multi-resistance to the usual ARV classes including PIs.


Assuntos
Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/uso terapêutico , HIV-1/efeitos dos fármacos , Piridinas/uso terapêutico , Pironas/uso terapêutico , Carga Viral/efeitos dos fármacos , Adulto , Terapia Antirretroviral de Alta Atividade , Contagem de Linfócito CD4 , Estudos de Coortes , Farmacorresistência Viral Múltipla , Quimioterapia Combinada , Feminino , França , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Ritonavir/uso terapêutico , Sulfonamidas
8.
J Antimicrob Chemother ; 66 Suppl 5: v67-70, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21680592

RESUMO

The high rates of antibiotic prescriptions and antimicrobial resistance in France motivated its participation in the European e-Bug school project concerning microbes, and infection transmission, prevention and treatment. The prospect of raising awareness among children, helping them to adopt suitable attitudes and behaviour towards infection transmission and treatment starting from childhood, generated enthusiastic support from relevant national educational and health institutions throughout the Project. France was actively involved in every stage: background research showed that the subject matter was best suited to the national science curricula of the fourth and fifth forms in junior schools, and the sixth and ninth forms in senior schools; a focus group study with junior and senior teachers elicited teachers' needs concerning teaching resources; and a qualitative and quantitative evaluation, after translation and pack review, enabled further adaptation of the packs. This evaluation showed an overall enthusiastic reception by teachers and their students in France, and reassured teachers on the ease of use of the Project's resources and students' progress. The e-Bug Project was launched through a national institutional implementation plan in September 2009 and orders for e-Bug tools increased rapidly. By the end of October, 57% of all senior science teachers and 16% of all junior school teachers had ordered the pack. France is one of the most frequent users of the e-Bug web site. The collaboration with both educational and health partners was particularly helpful to implementing the Project, and this was confirmed by the favourable reception and participation of teachers and students in the field.


Assuntos
Antibacterianos/uso terapêutico , Doenças Transmissíveis/transmissão , Instrução por Computador/métodos , Currículo , Educação em Saúde/métodos , Internet , Ciência , Adolescente , Criança , Doenças Transmissíveis/tratamento farmacológico , Farmacorresistência Bacteriana , Docentes , França , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Instituições Acadêmicas , Estudantes
9.
Clin Infect Dis ; 50(4): 549-51, 2010 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-20070235
10.
J Antimicrob Chemother ; 65(12): 2674-84, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20956353

RESUMO

OBJECTIVES: e-Bug, a junior and senior school educational programme to decrease the spread of infection and unnecessary antibiotic use, was developed and consisted of eight sections providing information on the spread, treatment and prevention of infection as well as basic information on microbes, both useful and harmful. Each section comprised teacher background information, lesson plans and an interactive student activity, and extension activities were also available for more able students. This study aimed to evaluate the effectiveness of the e-Bug pack in improving children's knowledge in these key areas, when used within the National Curriculum in England, France and the Czech Republic. METHODS: Junior (9-11 years) and senior (12-15 years) school classes were divided into either control or intervention groups for evaluation of the resource. Students were required to complete identical knowledge questionnaires at three timepoints (before, immediately after and 6 weeks after teaching), to assess knowledge change and retention. Teaching, using the e-Bug pack, was given by junior and senior school teachers. RESULTS: The junior e-Bug teaching pack demonstrated a significant improvement in student's knowledge in all sections and there was no significant decrease in student knowledge observed after a 6 week period. Knowledge improvement with the senior e-Bug pack varied between regions, although consistent improvement was observed for Gloucestershire (England) and Ostrava (Czech Republic). CONCLUSIONS: Although a success, modifications are required in both packs to further improve student knowledge and make the packs more appealing.


Assuntos
Antibacterianos/uso terapêutico , Instrução por Computador/métodos , Currículo , Educação em Saúde , Higiene/educação , Adolescente , Adulto , Criança , República Tcheca , Inglaterra , França , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Instituições Acadêmicas , Estudantes
11.
JMIR Mhealth Uhealth ; 8(4): e16140, 2020 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-32293581

RESUMO

BACKGROUND: The development of electronic health (eHealth) has offered the opportunity for remote care provision. eHealth addresses issues for patients and professionals favoring autonomy and compliance, respectively, while fostering closer links both between patients and health care professionals and among health care professionals themselves. OBJECTIVE: The aim of this study was to analyze the patterns of use, benefits, and perceived obstacles in eHealth among people living with HIV (PLHIV) and their caring physicians at hospitals. METHODS: An online multicenter observational survey was conducted October 15-19, 2018 in 51 medical units across France by means of self-administered questionnaires to collect sociodemographic and medical data, and perceptions of eHealth. Multiple correspondence analysis followed by mixed unsupervised classification were performed to analyze data of the respondents. RESULTS: A total of 279 PLHIV and 219 physicians responded to all parts of the questionnaire. Three groups of PLHIV were identified based on multivariate analysis. Group 1 comprised "eHealth believers" (121/279, 43.4%), who were more frequently above 60 years old and more likely to be receiving treatments other than antiretrovirals. Group 2, the "technology skeptics" (86/279, 30.8%), comprised more women with at least one child. Group 3, the "internet adopters" (72/279, 25.8%), were more frequently under 49 years of age, men who have sex with men, and more likely to use mobile apps for obtaining wellness/health information and related subjects. Three groups of physicians also emerged. Group 1 comprised those "strongly confident in eHealth" (95/219, 43.4%), who more frequently used mobile apps for wellness/health information and were more likely to accept prescription assistance software. Group 2 comprised physicians "strongly opposed to eHealth" (80/219, 36.5%), frequently asserting that eHealth challenges confidentiality. Group 3 were "open to eHealth" (44/219, 20.1%), comprising a higher proportion of infectious disease specialists, and were more likely to believe that medical apps are useful for patient education and information. No link was found between the groups of PLHIV and physicians. CONCLUSIONS: The literature on eHealth mainly classifies people as enthusiasts and skeptics; however, we identified a third profile among both PLHIV and physicians, albeit without a direct link between them. For PLHIV, this third group is attentive to eHealth for improving their health condition, and for physicians, this group considers eHealth to offer benefits to patients and their own practice.


Assuntos
Infecções por HIV , Médicos , Minorias Sexuais e de Gênero , Telemedicina , Atitude , Criança , Eletrônica , Feminino , França/epidemiologia , Infecções por HIV/epidemiologia , Infecções por HIV/terapia , Homossexualidade Masculina , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários
12.
Clin Infect Dis ; 49(9): 1433-40, 2009 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-19807275

RESUMO

BACKGROUND: The positive impact of opioid substitution treatment (OST) on opioid-dependent individuals with human immunodeficiency virus (HIV) infection is well documented, especially with regard to adherence to highly active antiretroviral therapy (HAART). We used the data from a 5-year longitudinal study of the MANIF 2000 cohort of individuals infected with HIV (as a result of injection drug use) and receiving HAART to investigate the predictors of long-term virological success. Design. Data were collected every 6 months from outpatient hospital services delivering HIV care in France. We selected all patients who were receiving HAART for at least 6 months (baseline visit) and who had indications for OST (ie, still dependent on opioids). We selected a total of 113 patients, accounting for a total of 562 visits for all the analyses. METHODS: Long-term virological success was defined as an undetectable viral load after at least 6 months on HAART. Retention in OST was defined as the time interval between the last initiation or reinitiation of OST during HAART follow-up and any given visit on OST. A mixed logistic model was used to identify predictors of long-term virological success. RESULTS: At baseline, 53 patients were receiving buprenorphine, 28 patients were receiving methadone, and 32 patients were not on OST. The median duration of OST was 25 months (range, 3-42 months). In the multivariate analysis, after adjustment for significant predictors of long-term virological success such as adherence to HAART and early virological response, retention in OST was associated with long-term virological success (odds ratio, 1.20 per 6-month increase; 95% confidence interval, 1.09-1.32). CONCLUSIONS: Our study presents important evidence of the positive impact of retention in OST on HIV outcomes. Increasing access to OST based on a comprehensive model of care for HIV-infected patients who have indications for OST may foster adherence and ensure long-term response to HAART.


Assuntos
Infecções por HIV/tratamento farmacológico , Entorpecentes/uso terapêutico , Adulto , Terapia Antirretroviral de Alta Atividade , Buprenorfina/uso terapêutico , Feminino , Humanos , Masculino , Metadona/uso terapêutico , Cooperação do Paciente , Resultado do Tratamento
13.
Clin Infect Dis ; 49(12): 1950-4, 2009 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-19911986

RESUMO

Among 1121 patients (90% Caucasian) infected by the human immunodeficiency virus (HIV), the glomerular filtration rate increased (+0.72 mL/min/1.73 m(2)/month) from treatment initiation to month 16 (the rate increase was lower among men and those with low body mass index, AIDS, or receipt of indinavir), then remained stable up to 7 years. Kidney function should be monitored in patients previously exposed to indinavir.


Assuntos
Fármacos Anti-HIV/administração & dosagem , Infecções por HIV/tratamento farmacológico , Rim/fisiopatologia , Adolescente , Adulto , Idoso , Contagem de Linfócito CD4 , Estudos de Coortes , Quimioterapia Combinada , Feminino , Taxa de Filtração Glomerular , Infecções por HIV/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade
14.
Antimicrob Agents Chemother ; 53(7): 2934-9, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19451297

RESUMO

The MONARK study was a pilot randomized trial comparing the safety and efficacy of lopinavir-ritonavir (LPV/r) monotherapy to those of LPV/r-zidovudine-lamivudine triple therapy for antiretroviral-naïve human immunodeficiency virus type 1 (HIV-1)-infected patients. Resistance testing was performed at the time of initial screening and at the time of virological failure (defined to include low-level viremia with >50 and <400 HIV-1 virus RNA copies/ml of plasma). Changes from the baseline sequences, including mutations noted on the 2008 International AIDS Society-USA list of resistance-associated protease mutations, were considered. Drug resistance testing was performed for 38 patients (5 of 53 on triple therapy and 33 of 83 on monotherapy). By week 96 (W96), virus samples from 18 of 33 patients in the monotherapy arm showed changes from baseline sequences, and 5 of these patients had viruses with major protease inhibitor (PI) resistance-associated mutations (M46I at W40, L76V at W48, M46I and L76V at W48, L10F and V82A at W72, and L76V at W84). Data on virus phenotypes detected at the time of initial screening and the time of virological failure were available for four patients in whom major PI resistance mutations developed, and these data revealed a mean increase of 2.2-fold (range, 0.75- to 4.6-fold) in the LPV 50% inhibitory concentration. All three patients in whom the L76V PI resistance mutation developed were infected with HIV-1 subtype CRF02_AG. In the triple-therapy group, no major PI resistance mutation was selected among the three patients with protease changes by W48. No association between the baseline CD4 cell count and the viral load, the W4 and final viral loads, or the final LPV trough concentration and the emergence of a major PI resistance mutation was found. Major PI resistance-associated mutations were detected in 5 (6%) of 83 patients treated with LPV/r monotherapy, suggesting that LPV/r monotherapy is an inappropriate first option. The mutation L76V may be considered in further studies of lopinavir resistance.


Assuntos
Inibidores da Protease de HIV/uso terapêutico , Lamivudina/uso terapêutico , Pirimidinonas/uso terapêutico , Ritonavir/uso terapêutico , Zidovudina/uso terapêutico , Farmacorresistência Viral/genética , Infecções por HIV/tratamento farmacológico , Infecções por HIV/genética , Humanos , Lopinavir , Resultado do Tratamento
15.
J Antimicrob Chemother ; 64(3): 599-606, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19602563

RESUMO

OBJECTIVES: The aim of this study was to identify factors associated with non-adherence over a 10 year follow-up of the APROCO-COPILOTE cohort during the maintenance phase of highly active antiretroviral therapy (HAART). METHODS: Overall, 1010 patients participated in this analysis, each having had at least 12 months of follow-up after HAART initiation and at least one self-reported adherence measure available during the follow-up period (month 12-month 120). Data collection was based on clinical records and self-administered questionnaires that gathered patients' psychosocial characteristics and experience with HIV disease and treatment. First, a generalized estimating equations (GEE) model was used to identify non-adherence predictors. Secondly, a Heckman two-stage approach was used in order to account for missing data bias and to measure the extent to which this could affect the results of the first model. RESULTS: Non-adherent behaviour was reported by 747 patients (2070 visits). After correcting for the bias due to missing data, non-adherence was independently associated with side effects, having a three times or more daily dosing regimen, experience of being at clinical stage B/C and being diagnosed as HIV-positive for <6 months. Non-adherence was more likely among patients who were younger, had children, were born in the European Union, had depressive symptoms, consumed alcohol daily and declared a lack of support from their main partner. Adjusting for missing outcome data changed the pattern of predictors. CONCLUSIONS: Reasons for non-adherence depended on both psychosocial conditions and treatment-related characteristics. To improve long-term patient outcomes for those at risk of adherence failure, tailor-made patient-specific psychosocial interventions and regimen-based strategies with improved tolerance need to be implemented.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade/métodos , Infecções por HIV/tratamento farmacológico , Cooperação do Paciente/estatística & dados numéricos , Fatores de Risco , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários
16.
AIDS Rev ; 10(4): 205-11, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-19092976

RESUMO

Since 1996 and the introduction of highly active antiretroviral therapies, multiple drugs have been developed. The best choice of drugs to start with still remains debated, especially regarding the choice between protease inhibitor-based or nonnucleoside reverse transcriptase inhibitor-based regimens. Regarding the regimen's ability to control viral replication, both have been proven to be very efficient in large settings of patients. Regarding short-term tolerability, both classes are responsible for various side effects in 10-25% of patients. Regarding long-term tolerability, protease inhibitor-based regimens may be responsible for metabolism abnormalities (hypertriglyceridemia, diabetes), although the role of the associated nucleoside reverse transcriptase inhibitor is not always clear. Patient adherence to the regimen is the cornerstone of efficacy. Resistance acquisition in case of poor adherence leading to treatment failure is a key issue regarding the ability to build future efficient regimens. Failure while using protease inhibitor-based regimens seldom leads to acquired resistance. Failure while using nonnucleoside reverse transcriptase inhibitor-based regimens leads to resistance, but the new available nonnucleoside reverse transcriptase inhibitors do not share the same patterns of resistance, so that the well-known "class resistance" in case of nonnucleoside reverse transcriptase inhibitor failure is no longer valid. Drug-drug interactions are frequent with all antiretrovirals and require close monitoring. In conclusion, protease inhibitor-based and nonnucleoside reverse transcriptase inhibitor-based regimens each have many advantages. The best choice will essentially be made taking into account the patients' characteristics.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade/tendências , Inibidores da Protease de HIV/uso terapêutico , Inibidores da Transcriptase Reversa/uso terapêutico , Ensaios Clínicos como Assunto , Farmacorresistência Viral , Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/efeitos adversos , Humanos , Cooperação do Paciente
17.
Antivir Ther ; 13(4): 591-9, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18672538

RESUMO

BACKGROUND: Standard-of-care for HIV-infected patients consists of combining three antiretroviral drugs. However, other therapeutic strategies could be beneficial given long-term toxicity and quality of life (QOL) issues associated with taking multiple antiretroviral drugs for many years. In the prospective, open label, randomized, pilot monotherapy antiretroviral Kaletra (MONARK) trial among antiretroviral-naive patients, lopinavir/ritonavir (LPV/r) monotherapy was found to be less suppressive for HIV RNA than a standard triple-drug therapy of LPV/r plus zidovudine/lamivudine (on-treatment analysis after 48 weeks). We present data from the MONARK trial concerning QOL and patient-reported symptoms. METHODS: Patient-reported symptoms were collected at baseline and at weeks 4, 12, 24 and 48 using a list of 22 symptoms. QOL was assessed at baseline, week 24 and week 48 using the six-domain World Health Organization QOL short form questionnaire for HIV-infected individuals including an evaluation of global health perception. RESULTS: Patients treated with the standard triple-drug therapy reported significantly more symptoms over 48 weeks of treatment than patients treated with LPV/r monotherapy (incidence rate ratio [95% confidence interval] 1.3 [1.1, 1.6] P=0.001 and 1.4 [1.2, 1.7] P=0.0004 for the total number of symptoms and the number of symptoms causing discomfort, respectively). No baseline differences and no significant changes were observed in the six QOL scores. The percentage of patients with a positive perception of their global health status increased significantly in the monotherapy arm from 32% at baseline to 67% at week 48 (P<0.0001). CONCLUSIONS: These results suggest that the number of self-reported symptoms could be used as a treatment-sensitive measure of patients' well-being in clinical trials.


Assuntos
Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV , Pirimidinonas , Qualidade de Vida , Ritonavir , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/uso terapêutico , Quimioterapia Combinada , Infecções por HIV/virologia , Inibidores da Protease de HIV/administração & dosagem , Inibidores da Protease de HIV/efeitos adversos , Inibidores da Protease de HIV/uso terapêutico , HIV-1/efeitos dos fármacos , HIV-1/fisiologia , Humanos , Lamivudina/administração & dosagem , Lamivudina/uso terapêutico , Lopinavir , Pirimidinonas/administração & dosagem , Pirimidinonas/efeitos adversos , Pirimidinonas/uso terapêutico , Inibidores da Transcriptase Reversa/administração & dosagem , Inibidores da Transcriptase Reversa/uso terapêutico , Ritonavir/administração & dosagem , Ritonavir/efeitos adversos , Ritonavir/uso terapêutico , Resultado do Tratamento , Carga Viral , Zidovudina/administração & dosagem , Zidovudina/uso terapêutico
18.
Pediatr Infect Dis J ; 27(11): 1033-5, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18955896

RESUMO

Pneumococcal nasopharyngeal carriage, serotype distribution, and penicillin-susceptibility were monitored among children attending daycare centers in France from 1999 to 2006 to assess the impact of pneumococcal conjugate vaccine and antibiotic-reducing policies. Pneumococcal carriage remained stable. Immunization rates reached 68% in 2006. Serotype distribution shifted significantly from vaccine serotypes to vaccine-related and nonvaccine serotypes. Antibiotic treatments fell by 50%.


Assuntos
Portador Sadio/epidemiologia , Creches , Nasofaringe/microbiologia , Infecções Pneumocócicas/epidemiologia , Streptococcus pneumoniae/isolamento & purificação , Pré-Escolar , Estudos Transversais , Feminino , França/epidemiologia , Vacina Pneumocócica Conjugada Heptavalente , Humanos , Lactente , Masculino , Vacinas Meningocócicas , Testes de Sensibilidade Microbiana , Resistência às Penicilinas , Vacinas Pneumocócicas , Sorotipagem , Streptococcus pneumoniae/classificação
19.
HIV Clin Trials ; 8(5): 320-7, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17956833

RESUMO

PURPOSE: To analyze the impact of self-reported fatigue and depressive symptoms on the quality of life (QOL) of patients co-infected with HIV and hepatitis C virus (HCV) not receiving anti-HCV therapy. METHOD: We used data from a cross-sectional survey conducted among 115 co-infected adults including an assessment of QOL (WHOQOL-HIV bref questionnaire), depressive symptomatology (Center for Epidemiological Studies Depression Scale [CES-D]), and fatigue (Fatigue Impact Scale [FIS]). RESULTS: Eighty-four percent of patients had been infected through injecting drug use (IDU). Half reported a history of depression or other psychiatric co-morbidities, 57% presented depressive symptoms, and 69% reported fatigue. FIS and CES-D scores accounted for 54% and 66% of total variance in psychological QOL and level of independence-related QOL, respectively, in a multivariate analysis adjusted for sociodemographic and clinical characteristics and alcohol or drug use. High FIS scores were independently associated with impaired physical QOL and social relationships, whereas high CES-D scores were independently associated with lower environmental QOL. CONCLUSION: Self-reported fatigue and depressive symptoms are the best indicators of co-infected patients' QOL. These two indicators could be more easily used for a better clinical management of co-infected patients and also introduced as patient outcome measures in clinical research.


Assuntos
Depressão/etiologia , Fadiga/etiologia , Infecções por HIV/complicações , Hepatite C/complicações , Qualidade de Vida , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estatística como Assunto
20.
Drug Alcohol Depend ; 86(2-3): 175-82, 2007 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-16930864

RESUMO

BACKGROUND: This study aimed to determine factors associated with higher levels of health related quality of life (HRQL) among individuals HIV-infected through drug injection and to evaluate the impact of injecting drug status and opiate substitution treatment (OST) on HRQL. METHODS: Two hundred and forty-three patients, enrolled in the MANIF cohort of patients HIV-infected through IDUs, participated. They completed a self-administered questionnaire, which included an HRQL evaluation (SF-12) and socio-demographic/clinical characteristics at the 42-month visit. Injecting drug status, OST and experience of negative life events (NLE) were collected at any follow-up visit in order to reconstitute individual trajectories. RESULTS: Among the 243 patients, 35% reported a normal mental HRQL and 37% a normal physical HRQL. Independent predictors of "normal" mental HRQL were social support from partner, being a former IDU, no experience of violence-related NLE and few self-reported HAART-related side effects. "Normal" physical HRQL was predicted by younger age, stable partner, being a former IDU (> or = 6 months), CD4 cell count > 500, no experience of financial-related NLE and few HAART self-reported side effects. CONCLUSIONS: As HRQL has been found to have a prognostic value on the survival of HIV patients infected through drug injection, then providing more comprehensive care (for example by paying more attention to patients' experience of stressful events, meeting their needs in psychosocial support and better management of perceived toxicity) could globally improve treatment outcomes in this vulnerable population.


Assuntos
Terapia Antirretroviral de Alta Atividade/efeitos adversos , Infecções por HIV/etiologia , Infecções por HIV/psicologia , Qualidade de Vida , Abuso de Substâncias por Via Intravenosa/complicações , Abuso de Substâncias por Via Intravenosa/psicologia , Adulto , Diarreia , Feminino , Humanos , Masculino , Inquéritos e Questionários
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