RESUMO
BACKGROUND AND PURPOSE: Non-motor symptoms (NMS) of Parkinson's disease (PD) have a major impact on health-related quality of life. This is the first randomized controlled trial to use the NMS Scale (NMSS) as a primary outcome to assess treatment effects on NMS in PD. METHODS: In this double-blind trial (NCT01300819), patients with PD and a total NMSS score ≥40 were randomized (2:1) to rotigotine or placebo, titrated over 1-7 weeks to optimal dose (≤8 mg/24 h for patients not receiving levodopa, ≤16 mg/24 h for patients receiving levodopa), maintained for 12 weeks. The primary outcome was change in NMSS total score from baseline to end of maintenance. Secondary outcomes were the nine NMSS domains, Unified Parkinson's Disease Rating Scale (UPDRS) III (motor) and the 39-item Parkinson's Disease Questionnaire (PDQ-39). RESULTS: In total, 283/349 (81.1%) randomized patients completed the trial; 211 rotigotine and 122 placebo were included in the full analysis set. The NMSS total score decreased by 23 (rotigotine) and 19 (placebo) points; the treatment difference was not statistically significant (-3.58; 95% confidence interval -8.43, 1.26; P = 0.147). Numerically greater than placebo improvements were detected in the 'mood/apathy' and 'miscellaneous' NMSS domains (P < 0.05). Treatment differences in UPDRS III (-2.60; -4.27, -0.92; P = 0.002) and PDQ-39 (-2.79; -5.21, -0.37; P = 0.024) favoured rotigotine. Adverse events reported more frequently with rotigotine were nausea, application site reactions, somnolence and headache. CONCLUSIONS: Rotigotine improvement in the multi-domain NMSS total score was not superior to placebo. A different sensitivity of individual NMSS domains to dopaminergic therapy and a large placebo effect may have contributed to these findings.
Assuntos
Agonistas de Dopamina/farmacologia , Avaliação de Resultados em Cuidados de Saúde , Doença de Parkinson/tratamento farmacológico , Tetra-Hidronaftalenos/farmacologia , Tiofenos/farmacologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Apatia/efeitos dos fármacos , Agonistas de Dopamina/administração & dosagem , Agonistas de Dopamina/efeitos adversos , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/complicações , Qualidade de Vida , Tetra-Hidronaftalenos/administração & dosagem , Tetra-Hidronaftalenos/efeitos adversos , Tiofenos/administração & dosagem , Tiofenos/efeitos adversos , Adesivo TransdérmicoRESUMO
Compliance is the appropriateness of patient behaviour to therapeutic prescriptions. Good compliance increases treatment efficacy although its constraints may harm quality of life. Factors affecting compliance are related to the patient, the disease, health-care workers, family and treatment itself. Psycho-sociologic theories have attempted to explain patient behaviour. In clinical trials, compliance has to be optimized, i.e. in the protocol, during the study and the statistical analysis. In real life, compliance concerns all those involved in health-care, particularly for education, training and motivation of the patients and their immediate environment. Observational surveys relating to compliance are needed to determine prioriites and to develop a "compliance approach" based on improving information and the use of tools for better therapeutic adherence. Evaluation of the quality of life and patient satisfaction aspects is necessary to validate this approach.
Assuntos
Tratamento Farmacológico , Cooperação do Paciente/estatística & dados numéricos , Qualidade de Vida/psicologia , Hábitos , Modelos Estatísticos , Cooperação do Paciente/psicologia , Satisfação do Paciente , Projetos de PesquisaRESUMO
BACKGROUND: Since eradication of HIV is unlikely, long-term management of the disease necessitates careful evaluation of the combinations of currently available drugs to determine the most potent and useful rational sequencing of regimens. OBJECTIVE: To determine the antiretroviral efficacy and tolerability of saquinavir soft gelatin capsule (SQV-SGC) plus zalcitabine (ddC) and stavudine (d4T), as first-line treatment in HIV-infected patients. DESIGN: Multicentre, open-label, non-comparative study. PATIENTS AND METHODS: Thirty-five asymptomatic, HIV-infected adults with no prior antiretroviral treatment, a CD4 count > or =250 cells/microL and baseline > or = 5000 HIV RNA copies/mL were included in the study. Patients received SQV-SGC 1200 mg three times a day (tid), ddC 0.75 mg tid and d4T 30 or 40 mg twice a day (bid) for 24 weeks. Plasma HIV RNA, CD4 and CD8 cell counts, HIV reverse transcriptase and protease resistance genotypes, SQV plasma concentration and tolerability were evaluated. RESULTS: At baseline, median HIV RNA (interquartile range) was 4.99 (4.81-5.48) log10 copies/mL, and median CD4 count was 370 (318-504) cells/microL (n = 35). At week 24, the median decrease in HIV RNA was 3.05 (2.19-3.68) log10 copies/mL. A viral load below the level of quantification (200 copies/mL and 20 copies/mL) was achieved in 63% and 34% of patients, respectively (intent-to-treat analysis). The only mutations detected were L90M substitutions in two patients. At week 24, the median CD4 count increased (P < 0.0001), and CD8 cell counts decreased (P < 0.0001), relative to baseline. In total, there were five cases of peripheral neuropathy (14%). Mean triglyceride and cholesterol levels remained within normal ranges. CONCLUSIONS: Triple therapy with SQV-SGC plus ddC and d4T is a reasonably well tolerated regimen that markedly and rapidly reduces viral load with immunological improvement. This combination is an effective additional therapeutic option, with an efficacy that compares favourably to other triple regimens used in HIV treatment.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/uso terapêutico , HIV-1 , Saquinavir/uso terapêutico , Adulto , Fármacos Anti-HIV/administração & dosagem , Cápsulas , Esquema de Medicação , Quimioterapia Combinada , França , Inibidores da Protease de HIV/administração & dosagem , Humanos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , RNA Viral , Saquinavir/administração & dosagem , Estavudina/administração & dosagem , Resultado do Tratamento , Carga Viral , Zalcitabina/administração & dosagemRESUMO
The objective of this study was to evaluate the antiretroviral efficacy and safety of ritonavir (600 mg twice a day [b.i.d.])-saquinavir (400 mg b.i.d.) compared to ritonavir (600 mg b.i.d.) in patients pretreated and receiving continued treatment with two nucleoside analogs. The study was placebo controlled, randomized, and double blind. Inclusion criteria included protease inhibitor naive status and a viral load of >10,000 copies/ml. The main end point was viral load at week 24. Forty-seven patients were included (25 given ritonavir and 22 given ritonavir-saquinavir) and monitored until week 48. At inclusion, 23% had had at least one AIDS-defining event. Previous treatment durations (mean and standard deviation) were 42 +/- 25 and 37 +/- 23 months, viral loads were 4.75 +/- 0.62 and 4.76 +/- 0.50 log(10) copies/ml, and CD4 cell counts were 236 +/- 126 and 234 +/- 125/mm(3) in the ritonavir and ritonavir-saquinavir groups, respectively. At week 24, viral loads were 2.81 +/- 1.48 and 2.08 +/- 1.14 log(10) copies/ml (P = 0.04) and CD4 cell counts were 330 +/- 151 and 364 +/- 185/mm(3) (P = 0.49) in the ritonavir and ritonavir-saquinavir groups, respectively. Similar results were observed at week 48. Moreover, at week 48, 40 and 68% (P = 0.05) and 28 and 59% (P = 0.03) of patients achieved viral suppression at below 200 and 50 copies/ml in the ritonavir and ritonavir-saquinavir groups, respectively. At week 24, six patients in the ritonavir group but only one in the ritonavir-saquinavir group had key mutations conferring resistance to protease inhibitors. Clinical and biological tolerances were similar in both groups. In nucleoside analog-pretreated patients, ritonavir-saquinavir has higher antiretroviral efficacy than and is as well tolerated as ritonavir alone.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/uso terapêutico , Ritonavir/uso terapêutico , Saquinavir/uso terapêutico , Adulto , Fármacos Anti-HIV/efeitos adversos , Fármacos Anti-HIV/sangue , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Seguimentos , Infecções por HIV/sangue , Infecções por HIV/virologia , Inibidores da Protease de HIV/efeitos adversos , Inibidores da Protease de HIV/sangue , Humanos , Testes de Função Hepática , Masculino , Ritonavir/efeitos adversos , Ritonavir/sangue , Saquinavir/efeitos adversos , Saquinavir/sangue , Carga ViralRESUMO
OBJECTIVE: This study was undertaken to determine the placental transfer of the human immunodeficiency virus protease inhibitor saquinavir. STUDY DESIGN: An ex vivo perfused human placental cotyledon model was used. Ten placental perfusion studies were performed, with concentrations of saquinavir in the maternal compartment ranging from 322 to 2197 ng/mL (within reference therapeutic ranges). Drug concentrations were determined by high-performance liquid chromatography. RESULTS: The mean (+/- SD) fetal transfer rate of saquinavir was 1.8% +/- 1.6%, and the mean (+/- SD) clearance index was 0.05 +/- 0.05. A mean (+/- SD) of 1.6% +/- 3.1% of the perfused saquinavir was retained by the cotyledon. The small amount of saquinavir that crossed the placenta corresponded to the fraction not bound to human serum albumin. CONCLUSION: The low rate of placental transfer of saquinavir suggests that use of this antiretroviral drug by pregnant women may not lead to significant exposure of the fetus.
Assuntos
Inibidores da Protease de HIV/metabolismo , Troca Materno-Fetal , Placenta/metabolismo , Saquinavir/metabolismo , Feminino , Humanos , Técnicas In Vitro , Cinética , GravidezRESUMO
The MIKADO trial was designed to evaluate the efficacy of stavudine-zalcitabine-saquinavir (soft gel capsule) [d4T-ddC-SQV(SGC)] in 36 naive patients (-3.3 log(10) units at week 24 [W24]). Among the 29 patients remaining on d4T-ddC-SQV(SGC) until W24, 10 harbored a virological failure (viral load of >200 copies/ml at W24) (group 1). To determine the reasons for therapeutic failure, genotypic and phenotypic resistance test results and SQV concentrations in plasma were analyzed and compared to those in successfully treated patients (viral load of <200 copies/ml at W24) (group 2). Reverse transcriptase and protease genotypic analyses in group 1 revealed the acquisition of only one SQV-associated mutation (L90M) in only two patients. There was no significant increase in the 50 or 90% inhibitory concentration of SQV in patients with or without the L90M mutation. However, the fact that two patients developed an L90M mutation only 4 weeks after relapse points to the need for genotypic resistance testing in the context of an initial failure of the antiretroviral regimen. At W24, the median SQV concentration in group 1 (71 ng/ml) was significantly lower than in group 2 (475 ng/ml), and the plasma SQV concentration was correlated with the viral load at W24 (r = -0.5; P<0.05) and with the drop in viral load between day 0 and W24 (r = -0.5; P<0.01). These results and the fact that the plasma SQV concentrations in the two groups prior to relapse (W12) were not significantly different strongly suggest that the early failure of this combination is not due to viral resistance but to a lack of compliance, pharmacological variability, and drug interactions or a combination of these factors.
Assuntos
Fármacos Anti-HIV/farmacologia , Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , HIV-1/efeitos dos fármacos , Mutação , Resistência Microbiana a Medicamentos/genética , Quimioterapia Combinada , Genótipo , Infecções por HIV/virologia , HIV-1/genética , HIV-1/isolamento & purificação , Humanos , Fenótipo , RNA Viral/sangue , Inibidores da Transcriptase Reversa/uso terapêutico , Saquinavir/farmacocinética , Saquinavir/farmacologia , Saquinavir/uso terapêutico , Estavudina/farmacologia , Estavudina/uso terapêutico , Falha de Tratamento , Zalcitabina/farmacologia , Zalcitabina/uso terapêuticoRESUMO
BACKGROUND: Ritonavir is a potent inhibitor of cytochrome P4503A4 that strongly increases saquinavir bioavailability. In this study we assessed the safety and antiretroviral efficacy of the combination of these two compounds in patients pretreated and receiving continued treatment with zidovudine and lamivudine who were protease inhibitor naive and who had a CD4 cell counts below 200/mm3. METHODS: In this 48-week pilot study, all patients received 600 mg ritonavir and 400 mg saquinavir twice daily. Administration of zidovudine and lamivudine was continued without a change in previous doses. Viral load, CD4 cell count, and the emergence of resistance to the two protease inhibitors were evaluated repeatedly up to week 48. RESULTS: Sixteen patients were included in the study. Previous nucleoside analog treatment duration was 48+/-22 months (mean +/- SD). Two patients quit taking both protease inhibitors within 2 weeks. The ritonavir dose had to be reduced in 10 other patients because of side effects. Between inclusion and week 48, plasma viremia varied from 4.87+/-0.43 to 3.00+/-1.29 log10 copies/mL and CD4 cell counts ranged from 98+/-61 to 250+/-139/mm3. Ten patients (63%) had viral loads below 200 copies/mL and 7 (44%) had viral loads below 50 copies/mL. A single key mutation that conferred ritonavir resistance I84V and V82A/V developed in two patients. A mutation at codon 54 developed in another patient. These mutations were associated with repeated cessations of antiretroviral treatment. No lipodystrophy was observed. CONCLUSION: Ritonavir and saquinavir in combination are quite well tolerated and induce a high and sustained antiretroviral efficacy. A four-drug combination that includes these two protease inhibitors should be considered as a first line of treatment in patients with low CD4 cell counts.
Assuntos
Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Fármacos Anti-HIV/uso terapêutico , Inibidores da Protease de HIV/uso terapêutico , Lamivudina/uso terapêutico , Inibidores da Transcriptase Reversa/uso terapêutico , Ritonavir/uso terapêutico , Saquinavir/uso terapêutico , Zidovudina/uso terapêutico , Síndrome da Imunodeficiência Adquirida/diagnóstico , Síndrome da Imunodeficiência Adquirida/imunologia , Adulto , Contagem de Linfócito CD4/efeitos dos fármacos , DNA Viral/efeitos dos fármacos , DNA Viral/genética , Esquema de Medicação , Resistência a Medicamentos , Quimioterapia Combinada , Feminino , Genótipo , Inibidores da Protease de HIV/efeitos adversos , Humanos , Lamivudina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Mutação/efeitos dos fármacos , Projetos Piloto , Reação em Cadeia da Polimerase , Inibidores da Transcriptase Reversa/efeitos adversos , Ritonavir/efeitos adversos , Saquinavir/efeitos adversos , Índice de Gravidade de Doença , Fatores de Tempo , Carga Viral , Zidovudina/efeitos adversosAssuntos
Hipersensibilidade a Drogas/etiologia , Inibidores da Protease de HIV/efeitos adversos , Nelfinavir/efeitos adversos , Urticária/induzido quimicamente , Urticária/terapia , Adulto , Linfócitos T CD4-Positivos/imunologia , Dessensibilização Imunológica , Hipersensibilidade a Drogas/terapia , Infecções por HIV/terapia , Inibidores da Protease de HIV/uso terapêutico , Humanos , Masculino , Nelfinavir/uso terapêuticoRESUMO
Assessment of the quality of life (QoL) of human immunodeficiency virus (HIV)-infected subjects is often based on questionnaires in which the items or questions are not seen to be relevant by patients, nor by the users of the data obtained. It therefore seemed appropriate to return to the issue. The methodological and bibliographical research as well as the consultations we conducted convinced us that the elaboration of a new questionnaire was both necessary and possible. In order to do so, we adopted methodological principles based on the Sickness Impact Profile development methodology. First a bibliographical research was conducted in order to study instruments already used for HIV infection. Then, experts concerned with HIV infection and members of patients' associations were interviewed to assess how opportune the development of a new instrument could be. Following this, a methodology was established for the design and construction of the new instrument. One hundred and eighteen candidate questions were generated from an analysis of the content of 20 patients' interviews, which were subsequently submitted to 102 patients, to obtain finally a set of 31 questions from the interpretation of the results obtained from classic psychometric analysis and also from non-classic methods (item response theory and Rasch model). The concept being measured is the impact of illness being experienced by HIV-infected subjects from their own perspective. The range of health states covered by this questionnaire relates to fairly mild conditions. Rasch analysis of this set of 31 questions (HIV-QL31) shows that it corresponds to one unidimensional construct. A single score can be calculated by simple summation of dichotomous response options. This score is highly reliable (Cronbach's alpha coefficient = 0.93) and is also discriminant regarding the severity of clinical status.
Assuntos
Infecções por HIV/psicologia , Psicometria/métodos , Qualidade de Vida , Inquéritos e Questionários , Adulto , Idoso , Análise Fatorial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos TestesRESUMO
BACKGROUND: Therapy for hepatitis B virus (HBV) infection is still unsatisfactory, particularly in patients who are co-infected with the human immunodeficiency virus (HIV). Lamivudine, a retroviral inhibitor, has been shown to have activity against HBV replication in vitro, in animal models, and in studies of immunocompetent persons. OBJECTIVE: To assess the efficacy of lamivudine in inhibiting HBV replication during a 12-month period in patients with both HBV and HIV infection. DESIGN: Prospective, open study. SETTING: University hospital. PATIENTS: 40 consecutive patients (39 men and 1 woman) infected with both HIV and HBV. All had progressive HIV disease; were refractory to or unable to tolerate therapies other than lamivudine; and received lamlvudine, 600 mg/d or 600 mg/d followed by 300 mg/d, as therapy for HIV disease. MEASUREMENTS: Serum concentrations of HBV DNA were assessed every 2 months by using molecular hybridization. Polymerase chain reaction (PCR) for HBV DNA was done at baseline and was done at months 2, 6, and 12 only if the HBV DNA concentration was less than 5 pg/mL. RESULTS: Two groups were retrospectively identified at baseline: patients with high HBV replication (serum HBV DNA concentrations > 5 pg/mL) (n = 30) and patients with low HBV replication (serum HBV DNA concentrations < 5 pg/mL) (n = 10). After 12 months of treatment, 26 of 27 patients (96.3% [95% Cl, 81% to 99.9%]) who had had high HBV replication at baseline had serum HBV DNA concentrations less than 5 pg/mL. However, PCR could still detect HBV DNA in serum in 11.5% (Cl, 2% to 30%) of these patients. Among patients who had had low HBV replication at baseline, the results of PCR for serum HBV DNA became negative in the 6 patients who had had a positive result on PCR at baseline. No serious adverse events occurred during treatment. CONCLUSION: Although this study was not a randomized, blinded trial, it suggests that lamivudine is active against.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Antivirais/uso terapêutico , Vírus da Hepatite B/efeitos dos fármacos , Hepatite B/tratamento farmacológico , Lamivudina/uso terapêutico , Inibidores da Transcriptase Reversa/uso terapêutico , Replicação Viral/efeitos dos fármacos , Infecções Oportunistas Relacionadas com a AIDS/sangue , Adulto , Antivirais/efeitos adversos , DNA Viral/sangue , Feminino , Hepatite B/sangue , Vírus da Hepatite B/fisiologia , Humanos , Lamivudina/efeitos adversos , Masculino , Estudos Retrospectivos , Inibidores da Transcriptase Reversa/efeitos adversosRESUMO
Patients with symptomatic gastrointestinal disease due to cytomegalovirus (CMV) were randomized to receive open-label ganciclovir (22) or foscarnet (26). Patients were stratified by disease site and concurrent gut infection. Response was assessed by a visual analogue score of symptoms, endoscopic appearances, histologic inflammation, and numbers of CMV inclusions. In each treatment group, 73% had a complete or good clinical response; 83% of foscarnet-treated and 85% of ganciclovir-treated patients showed response by endoscopy, and inclusion bodies disappeared from follow-up biopsies in 73% of these. Most patients (35) developed further evidence of CMV disease during follow-up. The time to progression was not significantly different between recipients (16 weeks) and nonrecipients (13 weeks) of maintenance therapy, although patients were not randomized to receive maintenance or not. Survival in both treatment groups was < 40 weeks and was unaffected by maintenance treatment. Both ganciclovir and foscarnet are effective first-line treatments for gastrointestinal (GI) CMV infection. Maintenance therapy does not prevent progression of disease.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Infecções por Citomegalovirus/tratamento farmacológico , Foscarnet/uso terapêutico , Ganciclovir/uso terapêutico , Gastroenteropatias/virologia , Infecções Oportunistas Relacionadas com a AIDS/mortalidade , Adulto , Antígenos Virais/sangue , Antígenos Virais/urina , Citomegalovirus/isolamento & purificação , Infecções por Citomegalovirus/etiologia , Infecções por Citomegalovirus/mortalidade , Seguimentos , Foscarnet/efeitos adversos , Ganciclovir/efeitos adversos , Gastroenteropatias/tratamento farmacológico , Gastroenteropatias/mortalidade , Humanos , Mucosa Intestinal/patologia , Mucosa Intestinal/virologia , Pessoa de Meia-Idade , Taxa de Sobrevida , Fatores de TempoAssuntos
Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Antivirais/farmacologia , Infecções por HIV/complicações , Vírus da Hepatite B/efeitos dos fármacos , Hepatite B/tratamento farmacológico , Zalcitabina/análogos & derivados , Infecções Oportunistas Relacionadas com a AIDS/virologia , Adulto , Antivirais/uso terapêutico , Hepatite B/virologia , Vírus da Hepatite B/fisiologia , Humanos , Lamivudina , Masculino , Replicação Viral/efeitos dos fármacos , Zalcitabina/farmacologia , Zalcitabina/uso terapêuticoRESUMO
Several types of biliary tract abnormality of undetermined origin have been described among AIDS patients. The aims of this study are: (1) to evaluate whether biliary tree involvement is in fact one or several homogeneous morphological entities, (2) to specify the role of CMV or Cryptosporidium sp. infection, and (3) to evaluate the possible efficacy of treatment. Since ultrasound had revealed abnormality in the biliary tree, 26 consecutive AIDS patients underwent cholangiography. Cholangiograms enabled us to distinguish between two types of biliary tract involvement: (1) gradual and regular stenosis of the terminal portion of the common bile duct associated with dilation but without irregularity of the intrahepatic biliary ducts was present in 27% of our cases, and (2) distal stenosis of the extrahepatic biliary ducts combined with diffuse irregularity of the caliber of the intrahepatic bile ducts was present in 73% of our cases. Concomitant infection by CMV or Cryptosporidium sp. was significantly more frequent when intrahepatic duct irregularities were present (94%) than when absent (14%, P < 0.001). Anti-CMV treatment and sphincterotomy were unsuccessful in treating anomalies of the intrahepatic biliary tract. Conversely, sphincterotomy caused rapid and lasting disappearance of pain in all our patients. In conclusion, biliary tract involvement in AIDS patients is of two types. CMV infection and infection by Cryptosporidium sp. are most frequent when the large intrahepatic ducts are implicated.
Assuntos
Síndrome da Imunodeficiência Adquirida/complicações , Doenças dos Ductos Biliares/etiologia , Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Infecções Oportunistas Relacionadas com a AIDS/etiologia , Infecções Oportunistas Relacionadas com a AIDS/terapia , Síndrome da Imunodeficiência Adquirida/diagnóstico , Síndrome da Imunodeficiência Adquirida/epidemiologia , Síndrome da Imunodeficiência Adquirida/terapia , Adulto , Doenças dos Ductos Biliares/diagnóstico , Doenças dos Ductos Biliares/epidemiologia , Doenças dos Ductos Biliares/terapia , Sistema Biliar/diagnóstico por imagem , Colangiografia , Terapia Combinada , Criptosporidiose/diagnóstico , Criptosporidiose/epidemiologia , Criptosporidiose/etiologia , Criptosporidiose/terapia , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/epidemiologia , Infecções por Citomegalovirus/etiologia , Infecções por Citomegalovirus/terapia , Endoscopia do Sistema Digestório , Feminino , HIV-1 , Humanos , Masculino , Estudos Prospectivos , UltrassonografiaAssuntos
Foscarnet/efeitos adversos , Doenças da Vulva/induzido quimicamente , Adulto , Feminino , Foscarnet/uso terapêutico , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Humanos , Síndrome de Necrose Retiniana Aguda/complicações , Síndrome de Necrose Retiniana Aguda/tratamento farmacológico , Úlcera/induzido quimicamenteRESUMO
The pharmacokinetics of foscarnet were evaluated in 11 AIDS patients with cytomegalovirus disease after twice-daily infusion of 90 mg/kg of body weight for 2 weeks. All patients were hydrated during foscarnet infusion. Blood and urine samples were collected on days 1, 7, and 14 of therapy. Foscarnet concentrations were measured by high-pressure liquid chromatography. Despite large interindividual variations, no significant differences were seen between day 1, day 7, and day 14 concentrations in plasma. Mean peak and trough concentrations on day 14 of therapy were 605 +/- 118 and 52 +/- 59 microM, respectively. In all patients, peak concentrations were well above those necessary to inhibit cytomegalovirus. Pharmacokinetic parameters remained stable throughout the study. On day 14, the mean half-life was 3.4 h, total and renal clearances were 118 and 92 ml/min, respectively, and the volume of distribution was 0.6 liter/kg. These data and previous clinical trials demonstrate that this more convenient dosage regimen can be safely used for patients with cytomegalovirus disease. The side effects were comparable to those reported with other dosage regimens, although no renal impairment was seen in this study, probably because of the hydration.
Assuntos
Síndrome da Imunodeficiência Adquirida/complicações , Antivirais/farmacocinética , Infecções por Citomegalovirus/tratamento farmacológico , Foscarnet/farmacocinética , Adulto , Antivirais/uso terapêutico , Cromatografia Líquida de Alta Pressão , Creatinina/metabolismo , Infecções por Citomegalovirus/complicações , Feminino , Foscarnet/uso terapêutico , Meia-Vida , Humanos , Infusões Intravenosas , MasculinoRESUMO
We have evaluated the effects of induction therapy with foscarnet 100 mg/kg b.i.d. via i.v. infusion in 60 AIDS patients with cytomegalovirus (CMV) retinitis and compared the findings with those in 37 such patients receiving a foscarnet induction regimen of 60 mg/kg t.i.d. via i.v. infusion. Induction therapy was given for at least 3 weeks, with the treatment period being extended in cases of slow resolution of retinitis. There was no significant difference between response rates in the two groups, with ophthalmologic response being observed in 52 (96%) of 54 evaluable b.i.d. patients and 33 (97%) of 34 evaluable t.i.d. patients over mean durations of therapy of 26 and 27 days, respectively; complete and partial responses were observed in 91 and 6%, respectively, of b.i.d. patients and 85 and 12%, respectively, of t.i.d. patients. Foscarnet was discontinued because of adverse events in 3 (3%) of 97 patients, with treatment being stopped in 2 patients because of renal insufficiency and in 1 patient because of an acute neurologic disorder. Serum creatinine concentrations increased significantly in both the b.i.d. group (from 82 to 98 mumol/L, p less than 0.01) and the t.i.d. group (from 73 to 122 mumol/L, p less than 0.001), with the difference between increases not being statistically significant. Serum creatinine concentrations greater than 200 mumol/L were observed in two b.i.d. patients and four t.i.d. patients; in four cases, concomitant medications or conditions contributed to renal impairment. Hypocalcemia of less than 1.75 mmol/L occurred in 18% of b.i.d. patients and 28% of t.i.d. patients during treatment (p = 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Antivirais/administração & dosagem , Infecções por Citomegalovirus/tratamento farmacológico , Ácido Fosfonoacéticos/análogos & derivados , Retinite/tratamento farmacológico , Síndrome da Imunodeficiência Adquirida/complicações , Adulto , Antivirais/efeitos adversos , Antivirais/uso terapêutico , Infecções por Citomegalovirus/complicações , Esquema de Medicação , Tolerância a Medicamentos , Feminino , Foscarnet , Humanos , Masculino , Pessoa de Meia-Idade , Ácido Fosfonoacéticos/administração & dosagem , Ácido Fosfonoacéticos/efeitos adversos , Ácido Fosfonoacéticos/uso terapêutico , Retinite/complicaçõesRESUMO
In order to evaluate the long-term effects of splenectomy in patients with human immunodeficiency virus-related immune thrombocytopenic purpura (ITP), we studied retrospectively two populations of patients: 21 had undergone splenectomy and 18 had not. At the time of diagnosis the first population had on average lower platelet counts than the second one. After a mean follow-up of 47 +/- 9 months the situation has been reversed: the population that underwent splenectomy had significantly higher platelet counts than that without splenectomy (190.600 +/- 55.300/mm3 versus 91.500 +/- 55.300/mm3, P less than 0.001). Moreover 76 percent of the patients with splenectomy versus 50 percent in the population without splenectomy were in complete remission of ITP at the last follow-up. It therefore seems that splenectomy had a statistically positive effect on platelet counts without worsening the immune status. Indeed, the clinical course towards AIDS was the same in both populations (35 percent in patients with splenectomy and 22 percent without, P = NS). Following splenectomy, the total blood lymphocytes count was increased, especially the CD8 population, while the CD4 count remains unchanged; these findings seem to be a common feature after splenectomy.
Assuntos
Síndrome da Imunodeficiência Adquirida/complicações , Púrpura Trombocitopênica Idiopática/cirurgia , Esplenectomia , Adulto , Estudos de Avaliação como Assunto , Feminino , Seguimentos , Soropositividade para HIV/complicações , Humanos , Contagem de Leucócitos , Subpopulações de Linfócitos , Linfócitos , Masculino , Púrpura Trombocitopênica Idiopática/sangue , Púrpura Trombocitopênica Idiopática/etiologia , Estudos Retrospectivos , Fatores de TempoRESUMO
In a randomized trial conducted in AIDS patients requiring prophylaxis against pneumocystosis we compared two pentamidine salts, isethionate (I) and mesylate (M), and two nebulizers (a modified ultrasonic Ultraneb 99 Devilbiss nebulizer, and a disposable jet nebulizer). Patients were randomized to one or the other nebulizer and received alternatively, once every other week, the two pentamidine salts in the IMIM or MIMI order. Characteristics and the side effects of the two courses of each pentamidine salt, as well as drug delivery by each nebulizer during the first course, were studied in 48 patients. The ultrasonic nebulizer was more effective (nebulization time: 19.8 +/- 7.3 mn versus 30.7 +/- 11 mn) and produced less side-effects (FEV1 decrease: 186 +/- 677 versus 571 +/- 708 ml) than the jet nebulizer. The mesylate salt tended to produce more side-effects than the isethionate, but the difference was not significant (FEV1 decreases: 439 +/- 688 ml and 295 +/- 756 ml respectively). We concluded that the best therapeutic procedure is to use pentamidine isethionate delivered by the ultrasonic nebulizer.