RESUMO
This retrospective analysis was conducted to describe the characteristics of nucleoside-naïve hepatitis B e antigen (HBeAg)-positive patients with chronic hepatitis B, who achieved hepatitis B surface antigen (HBsAg) loss during entecavir or lamivudine therapy. HBeAg-positive adults with chronic hepatitis B, elevated serum alanine aminotransferase, and compensated liver disease were randomized to double-blind treatment for up to 96 weeks with entecavir 0.5 mg/day or lamivudine 100 mg/day. HBsAg and hepatitis B virus (HBV) DNA were measured at regular intervals during and off-treatment follow-up. Through a maximum duration of 96 weeks on-treatment and 24 weeks off-treatment, HBsAg loss was confirmed in 18/354 (5.1%) patients treated with entecavir and 10/355 (2.8%) patients treated with lamivudine. Among the 28 patients with confirmed HBsAg loss, 27 (96%) achieved HBV DNA <300 copies/mL, and 27 (96%) achieved confirmed HBeAg loss. All entecavir recipients with HBsAg loss had HBV DNA <300 copies/mL. Caucasian patients, and those infected with HBV genotype A or D, were significantly more likely to lose HBsAg. This retrospective analysis of data from a randomized, global phase three trial shows that confirmed loss of HBsAg occurred in 5% of nucleoside-naïve HBeAg-positive patients treated with entecavir, and that HBsAg loss is associated with sustained off-treatment suppression of HBV DNA.
Assuntos
Antivirais/uso terapêutico , Guanina/análogos & derivados , Antígenos de Superfície da Hepatite B/sangue , Antígenos E da Hepatite B/sangue , Hepatite B Crônica/tratamento farmacológico , Lamivudina/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Alanina Transaminase/sangue , DNA Viral/sangue , Método Duplo-Cego , Feminino , Guanina/uso terapêutico , Vírus da Hepatite B/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Carga Viral , Adulto JovemRESUMO
Entecavir is a potent inhibitor of hepatitis B virus (HBV) polymerase. The efficacy and safety of entecavir in nucleoside-naïve patients with hepatitis B virus e antigen (HBeAg)-positive chronic hepatitis B was established in a large, international, double-dummy study (ETV-022) where patients were randomized to entecavir 0.5 mg/day (n = 354) or lamivudine 100 mg/day (n = 355) once daily. ETV-022 had a 52-week blinded treatment phase, followed by an extended blinded treatment phase for up to 44 additional weeks (96 weeks total). Treatment was discontinued for patients achieving a protocol-defined response as determined by patient management criteria that intended to test the possibility of finite therapy, which has not previously been studied for entecavir or other anti-HBV agents in a large trial. Early results from this study have been previously presented/published separately. This paper compiles the results of up to 2 years of treatment for protocol-defined responders, virologic responders and nonresponders. For responders who discontinued therapy (per protocol), 24-week off-treatment evaluation is presented to provide a more 'complete picture' of what clinicians can expect when treating nucleoside-naïve HBeAg-positive patients with chronic hepatitis B. For patients who discontinued therapy because of nonresponse (nonresponders) and subsequently entered the rollover study ETV-901, follow-up results, including resistance profile, are provided.
Assuntos
Antivirais , Guanina/análogos & derivados , Antígenos E da Hepatite B/sangue , Hepatite B Crônica/tratamento farmacológico , Lamivudina , Antivirais/administração & dosagem , Antivirais/efeitos adversos , Antivirais/farmacologia , Antivirais/uso terapêutico , DNA Viral/sangue , Relação Dose-Resposta a Droga , Método Duplo-Cego , Farmacorresistência Viral , Guanina/administração & dosagem , Guanina/efeitos adversos , Guanina/farmacologia , Guanina/uso terapêutico , Vírus da Hepatite B/efeitos dos fármacos , Hepatite B Crônica/virologia , Humanos , Lamivudina/administração & dosagem , Lamivudina/efeitos adversos , Lamivudina/farmacologia , Lamivudina/uso terapêutico , Testes de Sensibilidade Microbiana , Fatores de Tempo , Resultado do TratamentoRESUMO
In patients with AIDS, isolation of cytomegalovirus (CMV) from respiratory secretions is common. It is often found with other pathogens, which has led to debate regarding its role as a primary pulmonary pathogen. A retrospective investigation of patients with AIDS and CMV as a sole pulmonary isolate was performed in an attempt to describe their clinical presentation and course. All patients admitted to the hospital with pneumonia and with BAL or transbronchial biopsy (TBB) specimen positive for CMV between 1991 and 1994 were identified through a review of inpatient records. Inclusion criteria included positive CMV cultures from BAL, cytomegalic inclusion bodies from BAL or TBB, and thorough documentation of the absence of other pulmonary pathogens. Nine patients met the inclusion criteria for CMV pneumonitis. Seven were male and two were female, ages 26 to 44 years, and all had a history of opportunistic infections. Typical clinical presentation was characterized by increased respiratory rate, hypoxemia, and diffuse interstitial infiltrates. The mean CD4 count was 29.6 (+/- 22) cells per cubic millimeter, mean lactate dehydrogenase level was 414 (+/- 301) IU/L, and in seven patients in whom CMV antigen was measured it was greater than 50 positive cells per 200,000 WBCs. Three untreated patients died of respiratory failure and three had autopsy confirmation of CMV pneumonia. Five patients were treated with anti-CMV therapy for at least 2 weeks, and all demonstrated improvement in symptoms, oxygen saturation, and chest radiograph. At 3 months follow-up, all five patients were asymptomatic with no pulmonary symptoms. At 6 months follow-up, three of the five patients remained asymptomatic; the other two died of other opportunistic infections. In at least these nine patients, CMV represented a primary pulmonary pathogen. Patients who were treated responded quickly and were able to be discharged home from the hospital with marked improvement in their symptoms. We recommend that clinicians consider this diagnosis in the proper setting and consider treatment with anti-CMV therapy.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/virologia , Infecções por Citomegalovirus/complicações , Citomegalovirus/patogenicidade , Pneumonia por Pneumocystis/virologia , Pneumonia Viral/complicações , Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/microbiologia , Adulto , Antivirais/uso terapêutico , Brônquios/patologia , Líquido da Lavagem Broncoalveolar , Citomegalovirus/isolamento & purificação , Infecções por Citomegalovirus/tratamento farmacológico , Feminino , Ganciclovir/uso terapêutico , Humanos , Masculino , Pneumonia por Pneumocystis/complicações , Pneumonia por Pneumocystis/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Estudos RetrospectivosRESUMO
A 47-year-old homosexual man with human immunodeficiency virus infection and CD4+ cell count of 444 per mm3, and with a viral load of 95,720 copies per mL, developed a rapidly progressive cerebellar lesion one month after undergoing coronary artery bypass graft. Diagnostic data were unremarkable with the exception of the magnetic resonance imaging that revealed multiple subcortical and cerebellar lesions consistent with a demyelinating process. The patient died within two months. Postmortem examination of the cerebellum revealed acute phase progressive multifocal leukoencephalopathy. This case demonstrates that multifocal leukoencephalopathy must be considered in HIV+ patients in the setting of neurologic deterioration with radiographic evidence of demyelination regardless of CD4+ count.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Leucoencefalopatia Multifocal Progressiva/diagnóstico , Antivirais/administração & dosagem , Contagem de Linfócito CD4 , Cerebelo/patologia , Ponte de Artéria Coronária/efeitos adversos , Quimioterapia Combinada , Evolução Fatal , HIV-1/imunologia , Humanos , Terapia de Imunossupressão/efeitos adversos , Leucoencefalopatia Multifocal Progressiva/imunologia , Leucoencefalopatia Multifocal Progressiva/virologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Carga ViralRESUMO
We report a case of successful treatment of encainide-induced ventricular tachycardia with 3% hypertonic saline. To our knowledge, no other report exists in the literature of this treatment for proarrhythmic ventricular tachycardia from a type 1C agent. Metabolic consequences of the treatment included severe hypernatremia, hyperosmolarity, hypocalcemia, and hypophosphatemia, which were reversible over 24 hours. In spite of the risks, treatment of incessant ventricular tachycardia induced by type 1C agents with hypertonic saline may be life saving.
Assuntos
Anilidas/efeitos adversos , Antiarrítmicos/efeitos adversos , Solução Salina Hipertônica/uso terapêutico , Taquicardia/induzido quimicamente , Anilidas/uso terapêutico , Antiarrítmicos/uso terapêutico , Estimulação Cardíaca Artificial , Cardioversão Elétrica , Emergências , Encainida , Hidratação , Humanos , Masculino , Pessoa de Meia-Idade , Solução Salina Hipertônica/efeitos adversos , Taquicardia/terapia , Desequilíbrio Hidroeletrolítico/etiologiaRESUMO
Human herpesvirus 8 (HHV-8) infection has been implicated in the etiology of Kaposi's sarcoma (KS), primary effusion lymphoma (PEL), and multicentric Castleman's disease (MCD), three diseases that frequently develop in immunocompromised, human immunodeficiency virus-positive individuals. One hypothesis that would account for different pathological manifestations of infection by the same virus is that viral genes are differentially expressed in heterogeneous cell types. To test this hypothesis, we analyzed the localization and levels of expression of two viral genes expressed in latent and lytic infections and the viral homologue of interleukin-6 (vIL-6). We show that PEL parallels KS in the pattern of latent and lytic cycle viral gene expression but that the predominant infected cell type is a B cell. We also show that MCD differs from KS not only in the infected cell type (B-cell and T-cell lineage) but also in the pattern of viral gene expression. Only a few cells in the lesion are infected and all of these cells express lytic-cycle genes. Of possibly greater significance is the fact that in a comparison of KS, PEL, and MCD, we found dramatic differences in the levels of expression of vIL-6. Interleukin-6 is a B-cell growth and differentiation factor whose altered expression has been linked to plasma cell abnormalities, as well as myeloid and lymphoid malignancies. Our findings support the hypothesis that HHV-8 plays an important role in the pathogenesis of PEL and MCD, in which vIL-6 acts as an autocrine or paracrine factor in the lymphoproliferative processes common to both.
Assuntos
Hiperplasia do Linfonodo Gigante/virologia , Herpesvirus Humano 8 , Interleucina-6/biossíntese , Linfoma/virologia , Sarcoma de Kaposi/virologia , Hiperplasia do Linfonodo Gigante/patologia , Expressão Gênica , Humanos , Interleucina-6/genética , Linfoma/patologia , Sarcoma de Kaposi/patologia , Transcrição GênicaRESUMO
The antiviral effect of stavudine (2', 3'-didehydro-3'-deoxythymidine) against human immunodeficiency virus (HIV) type 1 was measured in 15 HIV-infected patients at baseline and at weeks 4, 10, 22, 34, and 52 of therapy. Patients received 0.1, 0.5, 1.0, or 2.0 mg/kg/day of stavudine. At all time points examined during the 52 weeks of therapy, the median virus titers in peripheral blood mononuclear cells were decreased 1-2 logs, and median immune complex-dissociated antigen levels were reduced 37%-67% compared with baseline values. Plasma RNA content measured by polymerase chain reaction was reduced approximately 0.5 log from baseline median values at both time points examined (weeks 10 and 52). These data demonstrate that stavudine has a substantial and durable antiviral effect.
Assuntos
Antivirais/administração & dosagem , Infecções por HIV/tratamento farmacológico , HIV-1/efeitos dos fármacos , Estavudina/administração & dosagem , Complexo Antígeno-Anticorpo , Antivirais/uso terapêutico , Células Cultivadas , Antígenos HIV/sangue , Infecções por HIV/virologia , HIV-1/crescimento & desenvolvimento , HIV-1/isolamento & purificação , Humanos , Leucócitos Mononucleares/virologia , Reação em Cadeia da Polimerase , RNA Viral/sangue , Estavudina/uso terapêutico , Viremia/virologiaRESUMO
OBJECTIVE: To describe the characteristics and outcomes of the first 3 years of admissions to a dedicated skilled nursing facility for people with acquired immunodeficiency syndrome (AIDS). METHODS: Systematic chart review of consecutive admissions to a 30-bed, AIDS-designated long-term care facility in New Haven, Connecticut, from October 1995 through December 1998. RESULTS: The facility has remained filled to 90% or more of its bed capacity since opening. Of 180 patients (representing 222 admissions), 69% were male; mean age was 41 years; 57% were injection drug users; 71% were admitted directly from a hospital. Leading reasons for admission were (1) the need for 24-hour nursing/medical supervision, (2) completion of acute medical treatment, and (3) terminal care. On admission, the median Karnofsky score was 40, and median CD4+ cell count was 24/mm3; 48% were diagnosed with serious neurologic disease, 44% with psychiatric illness; patients were receiving a median of 11 medications on admission. Of 202 completed admissions, 44% of patients died, 48% were discharged to the community, 8% were discharged to a hospital. Median length of stay was 59 days (range 1 to 1,353). Early (< or = 6 months) mortality was predicted by lower admission CD4+ count, impairments in activities of daily living, and the absence of a psychiatric history; long-term stay (> 6 months) was predicted by total number of admission medications, neurologic disease, and dementia. Comparison of admissions from 1995 to 1996 to those in 1997 to 1998 indicated significantly decreased mortality rates and increased prevalence of psychiatric illness between the two periods (P < .01). CONCLUSIONS: A dedicated skilled nursing facility for people with AIDS can fill an important service need for patients with advanced disease, acute convalescence, long-term care, and terminal care. The need for long-term care may continue to grow for patients who do not respond fully to current antiretroviral therapies and/or have significant neuropsychiatric comorbidities. This level of care may be increasingly important not only in reducing lengths of stay in the hospital, but also as a bridge to community-based residential options in the emerging chronic disease phase of the AIDS epidemic.