RESUMO
BACKGROUND: Treatment of chronic hepatitis C virus (HCV) infection in HIV-1-co-infected individuals remains challenging due to numerous factors, including drug-drug interactions. The aim of this study was to assess the safety and pharmacokinetic (PK) profile of raltegravir and ribavirin when dosed separately and together. METHODS: Fourteen healthy volunteers [mean (standard deviation) age 35 (10) years, 71% male] entered this phase 1 PK study and received single-dose ribavirin (800 mg) on day 1 (phase 1). Following a washout period, subjects received raltegravir (400 mg twice daily) on days 15-19 (phase 2) and single-dose ribavirin (800 mg) with raltegravir (400 mg) on day 20 (phase 3). Intensive PK sampling was undertaken on days 1, 19 and 20 and differences in geometric mean ratios (GMRs) for PK parameters between study periods were assessed. RESULTS: No statistically significant differences in PK parameters were observed for raltegravir between phases 2 and 3. A statistically significant decrease in maximum plasma concentration (C(max)) and an increase in time to maximum plasma concentration (T(max)) were observed for ribavirin in phase 3 compared with phase 1 [GMR (95% confidence interval) 0.79 (0.62-1.00) and 1.39 (1.08-1.78), respectively], whereas no significant differences in other ribavirin PK parameters were observed between study phases. No clinically significant safety concerns were reported. CONCLUSIONS: The PK profile of ribavirin is altered when administered with raltegravir (reduced C(max) and increased T(max)), with no safety concerns identified. This is unlikely to be of clinical significance or have an impact on the antiviral effects of ribavirin in HIV-1- and HCV-co-infected subjects.
Assuntos
Antivirais/efeitos adversos , Antivirais/farmacocinética , Pirrolidinonas/efeitos adversos , Pirrolidinonas/farmacocinética , Ribavirina/efeitos adversos , Ribavirina/farmacocinética , Adolescente , Adulto , Antivirais/administração & dosagem , Quimioterapia Combinada , Feminino , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Pirrolidinonas/administração & dosagem , Raltegravir Potássico , Ribavirina/administração & dosagem , Adulto JovemRESUMO
Invasive fungal infections cause significant morbidity and mortality after lung transplantation. Fungal prophylaxis following lung transplantation is not standardised, with transplant centres utilising a variety of regimens. Posaconazole is a broad-spectrum antifungal triazole that requires further investigation within the setting of lung transplantation. This prospective, single-centre, observational study explored the pharmacokinetics of posaconazole oral suspension (POS) in the early perioperative period following lung transplantation in 26 patients. Organ recipients were scheduled to receive 400mg POS twice daily for 6 weeks as primary antifungal prophylaxis. Therapeutic drug monitoring (TDM) of serum posaconazole levels was performed in accordance with local clinical protocols. Bronchoalveolar lavage fluid (BALF) was sampled during routine bronchoscopies. Posaconazole levels were measured both in serum and BALF using mass spectrometry. Posaconazole levels were highly variable within lung transplant recipients during the perioperative period and did not achieve 'steady-state'. Serum posaconazole concentrations positively correlated with levels within the BALF (r=0.5527; P=0.0105). Of the 26 patients, 10 failed to complete the study for multiple reasons and so the trial was terminated early. Unlike study findings in stable recipients, serum posaconazole levels rarely achieved steady-state in the perioperative period; however, they do reflect the concentrations within the airways of newly transplanted lungs. The role of POS as primary prophylaxis in the perioperative period is uncertain, but if used TDM may be helpful for determining attainment of therapeutic levels.
Assuntos
Antifúngicos/administração & dosagem , Antifúngicos/farmacocinética , Líquido da Lavagem Broncoalveolar/química , Soro/química , Suspensões/administração & dosagem , Triazóis/administração & dosagem , Triazóis/farmacocinética , Adulto , Idoso , Quimioprevenção/métodos , Feminino , Humanos , Transplante de Pulmão , Masculino , Espectrometria de Massas , Pessoa de Meia-Idade , Estudos Prospectivos , Transplantados , Adulto JovemRESUMO
We report an HIV-positive man who re-acquires hepatitis B with evidence of serological protection which then resolves while on anti-retrovirals including tenofovir.
Assuntos
Adenina/uso terapêutico , Infecções por HIV/tratamento farmacológico , Vírus da Hepatite B/fisiologia , Organofosfonatos , Compostos Organofosforados/uso terapêutico , Inibidores da Transcriptase Reversa/uso terapêutico , Ativação Viral , Adenina/análogos & derivados , Adulto , Infecções por HIV/complicações , Anticorpos Anti-Hepatite B/sangue , Humanos , Masculino , TenofovirRESUMO
The purpose of this review is to provide an overview of sexual assault (in adults). In particular, the aim is to emphasize changes regarding medical, legal and management issues since the subject was reviewed in this journal in 1990. However some aspects will not have changed in the last 10 years.
Assuntos
Estupro/estatística & dados numéricos , Infecções Sexualmente Transmissíveis , Adolescente , Adulto , Assistência ao Convalescente/métodos , Fatores Etários , Anticoncepcionais Pós-Coito , Feminino , Medicina Legal , Humanos , Masculino , Anamnese/métodos , Exame Físico/métodos , Vigilância da População , Guias de Prática Clínica como Assunto , Prevalência , Estupro/legislação & jurisprudência , Estupro/prevenção & controle , Fatores de Risco , Infecções Sexualmente Transmissíveis/diagnóstico , Infecções Sexualmente Transmissíveis/epidemiologia , Infecções Sexualmente Transmissíveis/etiologia , Infecções Sexualmente Transmissíveis/terapia , Reino Unido/epidemiologiaRESUMO
We show that for a certain class of dynamics at the nodes the response of a network of any topology to arbitrary inputs is defined in a simple way by its response to a monotone input. The nodes may have either a discrete or continuous set of states and there is no limit on the complexity of the network. The results provide both an efficient numerical method and the potential for accurate analytic approximation of the dynamics on such networks. As illustrative applications, we introduce a quasistatic mechanical model with objects interacting via frictional forces and a financial market model with avalanches and critical behavior that are generated by momentum trading strategies.
Assuntos
Administração Financeira , Fricção , Modelos Teóricos , Plásticos , Simulação por Computador , ElasticidadeAssuntos
Infecções por HIV/transmissão , HIV-1 , Medicina Reprodutiva/organização & administração , Neoplasias Urogenitais/prevenção & controle , Terapia Antirretroviral de Alta Atividade/métodos , Anticoncepção , Transmissão de Doença Infecciosa/legislação & jurisprudência , Transmissão de Doença Infecciosa/prevenção & controle , Feminino , Infecções por HIV/terapia , Humanos , Masculino , Gravidez , Comportamento Sexual/ética , Comportamento Sexual/psicologia , Infecções Sexualmente Transmissíveis/prevenção & controle , Reino Unido , Neoplasias Urogenitais/terapiaAssuntos
Síndrome da Imunodeficiência Adquirida/complicações , Retinite por Citomegalovirus/etiologia , HIV-1 , Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Adulto , Terapia Antirretroviral de Alta Atividade , Contagem de Linfócito CD4 , Retinite por Citomegalovirus/tratamento farmacológico , Humanos , MasculinoRESUMO
Genital diseases include a wide range of lesions e.g. infectious and inflammatory. In most cases a clinical diagnosis is reached without the need for a biopsy. Nonetheless, a genital biopsy is safe and may help to confirm the diagnosis. We established a dedicated diagnostic biopsy clinic in 2003. Our objective was to evaluate the effectiveness of our diagnostic biopsy clinic and compare it with other Genitourinary medicine (GUM) clinics in the UK. A retrospective case-note study was performed on 71 patients referred to the biopsy clinic with persistent genital lesions over a 12-month period. Forty-seven biopsies were performed (71% biopsy rate). 43 specimens (92%) were appropriate for histopathological diagnosis. Of these 15% were lichen planus, 15% lichen sclerosis, 10% psoriasis, 7.5% each: eczema, Zoon's and non-specific balanitis. The remainder represented a variety of other conditions. In 27 cases (68%) the clinical diagnosis was consistent with the histological result. The possibility of self-referral and walk-in nature of our GUM service substantially decrease the waiting times for assessment of anogenital disorders. We had a lower biopsy rate for the diagnosis of non-specific balanitis (7.5%) compared with the average rate (21.5%) in 14 UK GUM clinics and good agreement between clinical and histological diagnosis. An empirical first treatment, with simple emollients before biopsy, appears to be a safe clinical approach for the treatment of non-specific balanitis. A multidisciplinary approach (GUM physicians, dermatologists and urologists/gynaecologists) could help prevent unnecessary biopsies and improve correlation between clinical and histological diagnosis.
Assuntos
Doenças do Ânus/diagnóstico , Biópsia , Doenças dos Genitais Femininos/diagnóstico , Doenças dos Genitais Masculinos/diagnóstico , Genitália/patologia , Dermatopatias/diagnóstico , Adulto , Doenças do Ânus/patologia , Balanite (Inflamação)/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Equipe de Assistência ao Paciente , Estudos Retrospectivos , Dermatopatias/patologiaRESUMO
Cervical tuberculosis is uncommon in the developed world. We describe a patient who attended a genitourinary medicine clinic, and who was found to have cervical tuberculosis, in association with HIV infection.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Tuberculose dos Genitais Femininos/diagnóstico , Doenças do Colo do Útero/diagnóstico , Adulto , Feminino , HumanosRESUMO
There is evidence from our own unit and other workers that many patients who have lipodystrophy on HAART given for HIV disease also have raised oestrogen levels and complain of low sexual desire. This hypothesis paper discusses a possible pathological mechanism for these changes--an increase in the number of fibroblasts and macrophages present in lipoatrophic areas that could convert testosterone to oestrogen by intracellular aromatisation. This process is known to be enhanced by increased levels of tumour necrosis factor, interleukin 6 (IL-6), and hydroxycorticosteroids present in many patients with HIV lipodystrophy. Treatment options are discussed, including aromatase inhibitors and testosterone.