Asunto(s)
Ritonavir , Tacrolimus , Humanos , Ritonavir/administración & dosificación , Tacrolimus/administración & dosificación , Tacrolimus/efectos adversos , Tacrolimus/sangre , Inmunosupresores/administración & dosificación , Inmunosupresores/efectos adversos , Masculino , Inhibidores de la Proteasa del VIH/administración & dosificación , Interacciones Farmacológicas , Infecciones por VIH/tratamiento farmacológico , Persona de Mediana Edad , Quimioterapia Combinada , Trasplante de RiñónRESUMEN
Kaposi sarcoma is a rare angioproliferative disease associated with human herpes virus-8 (HHV-8) infection. Kaposi sarcoma is frequent and aggressive in HIV-infected people, whereas the classic form (CKS) generally has an indolent course. Notably, all conventional therapies against Kaposi sarcoma have only temporary efficacy. We have previously shown that indinavir, a HIV protease-inhibitor with direct antiangiogenic and antitumor activity, is safe and effective in patients with early CKS, whereas effects are less prominent in advanced disease, probably due to the larger tumor mass. Therefore, the clinical response to indinavir was assessed in patients with advanced CKS after debulking chemotherapy. This was a monocentric phase 2 trial in elderly with progressive/advanced CKS treated with debulking chemotherapy and indinavir combined, followed by a maintenance phase with indinavir alone. Secondary endpoints included safety and Kaposi sarcoma biomarker evaluation.All evaluable patients (22) responded to debulking therapy. Out of these, 16 entered the indinavir maintenance phase. The overall response rate at end of maintenance was 75% (estimated median response-duration 43 months). Moreover, most responders showed further clinical improvements (lesion number/nodularity) during maintenance and post-treatment follow-up. Notably, after relapse, progressors did not require systemic Kaposi sarcoma therapy and showed clinical improvements (including disease stabilization) remaining on study. Responders also showed immune status amelioration with a consistent B-cell increase and positive changes of other biomarkers, including anti-HHV-8 natural killer activity. In advanced CKS a strategy combining indinavir and chemotherapy is safe and associated with high and durable response rates and it could be rapidly adopted for the clinical management of these patients. SIGNIFICANCE: This phase-2 trial showed that the HIV protease inhibitor indinavir may boost and extend the duration of the effects of chemotherapy in elderly with advanced progressive classic Kaposi sarcoma, without additional toxicity. Further, the amelioration of the immune status seen in responders suggests a better control of HHV-8 infection and tumor-cell killing. Thus, indinavir combined with chemotherapy may represent an important tool for the clinical management of classic Kaposi sarcoma in elderly patients.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Inhibidores de la Proteasa del VIH , Indinavir , Sarcoma de Kaposi , Humanos , Sarcoma de Kaposi/tratamiento farmacológico , Indinavir/uso terapéutico , Indinavir/administración & dosificación , Indinavir/efectos adversos , Masculino , Femenino , Anciano , Inhibidores de la Proteasa del VIH/uso terapéutico , Inhibidores de la Proteasa del VIH/administración & dosificación , Inhibidores de la Proteasa del VIH/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Anciano de 80 o más Años , Resultado del Tratamiento , Herpesvirus Humano 8RESUMEN
Atazanavir or ATV is an FDA-approved, HIV-1 protease inhibitor that belongs to the azapeptide group. Over time, it has been observed that ATV can cause multiple adverse side effects in the form of liver diseases including elevations in serum aminotransferase, indirect hyper-bilirubinemia, and idiosyncratic acute liver injury aggravating the underlying chronic viral hepatitis. Hence, there is an incessant need to explore the safe and efficacious method of delivering ATV in a controlled manner that may reduce the proportion of its idiosyncratic reactions in patients who are on antiretroviral therapy for years. In this study, we assessed ATV formulation along with Rosemary oil to enhance the anti-HIV-1 activity and its controlled delivery through self-nanoemulsifying drug delivery system or SNEDDS to enhance its oral bioavailability. While the designing, development, and characterization of ATV-SNEDDS were addressed through various evaluation parameters and pharmacokinetic-based studies, in vitro cell-based experiments assured the safety and efficacy of the designed ATV formulation. The study discovered the potential of ATV-SNEDDS to inhibit HIV-1 infection at a lower concentration as compared to its pure counterpart. Simultaneously, we could also demonstrate the ATV and Rosemary oil providing leads for designing and developing such formulations for the management of HIV-1 infections with the alleviation in the risk of adverse reactions.
Asunto(s)
Sulfato de Atazanavir , Infecciones por VIH , VIH-1 , Sulfato de Atazanavir/farmacocinética , Sulfato de Atazanavir/administración & dosificación , Infecciones por VIH/tratamiento farmacológico , Humanos , Animales , VIH-1/efectos de los fármacos , Emulsiones , Sistemas de Liberación de Medicamentos , Aceites Volátiles/administración & dosificación , Aceites Volátiles/química , Aceites Volátiles/farmacocinética , Aceites Volátiles/farmacología , Masculino , Inhibidores de la Proteasa del VIH/administración & dosificación , Inhibidores de la Proteasa del VIH/farmacocinética , Inhibidores de la Proteasa del VIH/uso terapéutico , Fármacos Anti-VIH/administración & dosificación , Fármacos Anti-VIH/farmacocinética , Fármacos Anti-VIH/química , Nanopartículas/administración & dosificación , Nanopartículas/química , Sistema de Administración de Fármacos con Nanopartículas/químicaAsunto(s)
Humanos , Infecciones por VIH/tratamiento farmacológico , Inhibidores de la Proteasa del VIH/administración & dosificación , Ritonavir/administración & dosificación , Síndrome de Lipodistrofia Asociada a VIH/inducido químicamente , Darunavir/administración & dosificación , Triglicéridos/sangre , Estudios Prospectivos , Inhibidores de la Proteasa del VIH/efectos adversos , Ritonavir/efectos adversos , Síndrome de Lipodistrofia Asociada a VIH/sangre , Sustitución de Medicamentos , Darunavir/efectos adversos , LDL-Colesterol/sangreRESUMEN
Abstract In this study, 275 patients in use of tenofovir were retrospectively followed-up for three years to evaluate risk factors involved in impaired renal function. Analysis of variance (ANOVA) and Tukey's test were used to verify any differences in creatinine levels and estimated clearance at 0, 6, 12, 24 and 36 months, adjusting for the co-variables sex, skin color, age >50 years, arterial hypertension, diabetes and the use of the ritonavir-boosted protease inhibitors (PI/r) lopinavir/r or atazanavir/r. The software package STATISTICA 10® was used for statistical analysis. The patients’ mean age was 43.2 ± 10.7 years. Systemic arterial hypertension (SAH) and diabetes were found in 20.4% and 8.7% of the patients, respectively. Overall, 96.7% were on tenofovir associated with lamivudine (TDF + 3TC), 39.3% on lopinavir/r, 29.8% on efavirenz, and 17.6% on atazanavir/r. There was a statistically significant difference in estimated creatinine clearance at 24 months, when the co-variables male (F = 3.95; p = 0.048), SAH (F = 6.964; p = 0.009), and age over 50 years (F = 45.81; p < 0.001) were taken into consideration. Analysis of the co-variable use of atazanavir/r showed a tendency toward an increased risk over time (F = 2.437; p = 0.063); however, no significant time interaction was seen. At 36-month, a statistically significant difference was found for age over 50 years, (F = 32.02; p < 0.05) and there was a significant time-by-sex interaction (F = 3.117; p = 0.0149). TDF was discontinued in 12 patients, one because of a femoral neck fracture (0.7%) and 11 due to nephrotoxicity (4%). Of these latter cases, 9/11 patients were also using protease inhibitors. These data strongly alert that tenofovir use should be individualized with careful attention to renal function especially in male patients, over 50 years, with SAH, and probably those on ATV/r.
Asunto(s)
Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Fármacos Anti-VIH/efectos adversos , Riñón/efectos de los fármacos , Tenofovir/efectos adversos , Fármacos Anti-VIH/administración & dosificación , Quimioterapia Combinada/efectos adversos , Estudios de Seguimiento , Tasa de Filtración Glomerular/efectos de los fármacos , Infecciones por VIH/tratamiento farmacológico , Inhibidores de la Proteasa del VIH/administración & dosificación , Inhibidores de la Proteasa del VIH/efectos adversos , Riñón/fisiopatología , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Tenofovir/administración & dosificaciónRESUMEN
INTRODUCTION: Since the emergence of antiretroviral therapy, the survival of patients infected with human immunodeficiency virus has increased. Non-adherence to this therapy is directly related to treatment failure, which allows the emergence of resistant viral strains. METHODS: A retrospective descriptive study of the antiretroviral dispensing records of 229 patients from the Center for Health Care, University Hospital, Federal University of Juiz de Fora, Brazil, was conducted between January and December 2009. RESULTS: The study aimed to evaluate patient compliance and determine if there was an association between non-adherence and the therapy. Among these patients, 63.8% were men with an average age of 44.0 ± 9.9 years. The most used treatment was a combination of 2 nucleoside reverse transcriptase inhibitors with 1 non-nucleoside reverse transcriptase inhibitor (55.5%) or with 2 protease inhibitors (28.8%). It was found that patients taking lopinavir/ritonavir with zidovudine and lamivudine had a greater frequency of inadequate treatment than those taking atazanavir with zidovudine and lamivudine (85% and 83.3%, respectively). Moreover, when the combination of zidovudine/ lamivudine was used, the patients were less compliant (χ2 = 4.468, 1 degree of freedom, p = 0.035). CONCLUSIONS: The majority of patients failed to correctly adhere to their treatment; therefore, it is necessary to implement strategies that lead to improved compliance, thus ensuring therapeutic efficacy and increased patient survival.
INTRODUÇÃO: A partir do surgimento da terapia antirretroviral, o paciente soropositivo teve sua sobrevida aumentada. A não adesão a essa terapia está relacionada diretamente à falência terapêutica, a qual propicia o aparecimento de cepas virais mais resistentes. MÉTODOS: Foi realizado um estudo retrospectivo e descritivo dos registros de dispensação de antirretrovirais de 229 pacientes do Centro de Atenção à Saúde do Hospital Universitário da Universidade Federal de Juiz de Fora, no período de janeiro a dezembro de 2009. RESULTADOS: Tal estudo teve por objetivo avaliar a adesão do paciente ao tratamento e se houve associação entre a não adesão e a terapêutica. Desses pacientes, 63,8% eram do sexo masculino e apresentavam idade média de 44,0 ± 9,9 anos. Foram realizados 28 esquemas terapêuticos diferentes. Dentre esses, os mais utilizados foram aqueles que combinavam 2 inibidores da transcriptase reversa análogos de nucleosídeos/nucleotídeos com 1 inibidor da transcriptase reversa não análogo de nucleosídeo (55,5%) ou com 2 inibidores de protease (28,8%). Foi verificado que os pacientes em uso de lopinavir/ritonavir ou atazanavir associados à zidovudina e lamivudina apresentaram maiores frequências de tratamento considerado inadequado (85% e 83,3%, respectivamente). Além disso, quando a combinação zidovudina/lamivudina esteve presente no esquema medicamentoso, os pacientes aderiram menos ao tratamento (χ2 = 4,468; grau de liberdade = 1; p = 0,035). CONCLUSÕES: A maioria dos pacientes realizava tratamento considerado inadequado. Portanto, é necessário implementar estratégias que conduzam à melhoria da adesão ao tratamento, a fim de garantir eficácia terapêutica e aumento da sobrevida do paciente.
Asunto(s)
Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Inhibidores de la Proteasa del VIH/uso terapéutico , Cooperación del Paciente , Fármacos Anti-VIH/administración & dosificación , Esquema de Medicación , Quimioterapia Combinada , Inhibidores de la Proteasa del VIH/administración & dosificación , Estudios RetrospectivosRESUMEN
Darunavir (DRV) is an HIV-1 protease inhibitor that is used together with a low boosting dose of ritonavir as part of an antiretroviral therapy (ART) regimen in treatment-experienced and naïve HIVpositive patients. In naïve and experienced patients with no DRV-mutations, DRV is licensed at the dose of 800 mg plus 100 mg of ritonavir once daily. We report our results in seven ART-experienced HIV-infected patients, in whom a reduced dose of darunavir/ritonavir (600/100 mg once daily) successfully controlled viral replication.
Asunto(s)
Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infecciones por VIH/tratamiento farmacológico , Inhibidores de la Proteasa del VIH/administración & dosificación , Ritonavir/administración & dosificación , Sulfonamidas/administración & dosificación , Quimioterapia Combinada , Infecciones por VIH/virología , Resultado del Tratamiento , Carga ViralRESUMEN
OBJECTIVES: To describe laboratory abnormalities among HIV-infected women and their infants with standard and increased lopinavir/ritonavir (LPV/r) dosing during the third trimester of pregnancy. METHODS: We evaluated data on pregnant women from NISDI cohorts (2002-2009) enrolled in Brazil, who received at least 28 days of LPV/r during the third pregnancy trimester and gave birth to singleton infants. RESULTS: 164 women received LPV/r standard dosing [(798/198 or 800/200 mg/day) (Group 1)] and 70 increased dosing [(> 800/200 mg/day) (Group 2)]. Group 1 was more likely to have advanced clinical disease and to use ARVs for treatment, and less likely to have CD4 counts > 500 cells/mm³. Mean plasma viral load was higher in Group 2. There were statistically significant, but not clinically meaningful, differences between groups in mean AST, ALT, cholesterol, and triglycerides. The proportion of women with Grade 3 or 4 adverse events was very low, with no statistically significant differences between groups in severe adverse events related to ALT, AST, total bilirubin, cholesterol, or triglycerides. There were statistically significant, but not clinically meaningful, differences between infant groups in ALT and creatinine. The proportion of infants with Grade 3 or 4 adverse events was very low, and there were no statistically significant differences in severe adverse events related to ALT, AST, BUN, or creatinine. CONCLUSION: The proportions of women and infants with severe laboratory adverse events were very low. Increased LPV/r dosing during the third trimester of pregnancy appears to be safe for HIV-infected women and their infants.
Asunto(s)
Femenino , Humanos , Recién Nacido , Masculino , Embarazo , Fármacos Anti-VIH/efectos adversos , Infecciones por VIH/tratamiento farmacológico , Inhibidores de la Proteasa del VIH/efectos adversos , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Pirimidinonas/efectos adversos , Ritonavir/efectos adversos , Fármacos Anti-VIH/administración & dosificación , Estudios de Cohortes , Infecciones por VIH/sangre , Inhibidores de la Proteasa del VIH/administración & dosificación , Tercer Trimestre del Embarazo , Complicaciones Infecciosas del Embarazo/sangre , Pirimidinonas/administración & dosificación , Factores de Riesgo , Ritonavir/administración & dosificaciónRESUMEN
De los 25 anti-retrovirales disponibles en el mercado, sólo 16 están autorizados en la edad pediátrica. Los antiretrovirales, pertenecientes a las tres primeras familias, usados desde hace dos décadas, continúan vigentes y son parte importante de la terapia anti-retroviral en niños naïve. Se describen las dosis, presentaciones y asociaciones actuales de estos fármacos en la edad pediátrica y además se comentan las nuevas co-formulaciones que permitirán disminuir el número de dosis, mejorar la tolerancia y por lo tanto conseguir mejor adherencia de los pacientes pediátricos.
Of the 25 antiretroviral drugs available in the market, only 16 are allowed for prescription in the pediatric patients. The antiretroviral, pertaining to the first three families, used for two decades, remain valid and are important components of antiretroviral therapy in naive children. We describe doses, presentations and current associations for these drugs in children, and also discuss new co-formulations that will reduce the number of doses, improve tolerance and therefore achieve better adherence of pediatric patients.
Asunto(s)
Niño , Humanos , Antirretrovirales/administración & dosificación , Infecciones por VIH/tratamiento farmacológico , Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Fármacos Anti-VIH/administración & dosificación , Esquema de Medicación , Inhibidores de la Proteasa del VIH/administración & dosificación , Transcriptasa Inversa del VIH/antagonistas & inhibidores , Inhibidores de la Transcriptasa Inversa/administración & dosificaciónRESUMEN
With the introduction of highly active antiretroviral therapy, a number of drugs have been developed. The best choice concerning which antiretroviral analogs to start is always under discussion, especially in the choice between non-nucleoside reverse transcriptase inhibitors-based therapies and ritonavir-boosted protease inhibitors. Both are proven to control viral replication and lead to immunological gain. The choice between a non-nucleoside analog reverse transcriptase inhibitor and a protease inhibitor as a third antiretroviral drug in the therapy should consider factors related to the individual, as well as the inclusion of the best therapy in the patient's daily activities and potential adherence. The protease inhibitor-based therapies showed similar efficacy among the various inhibitors with characteristics concerning the adverse events from each medicine. For the treatment of protease-resistant patients, darunavir and tipranavir showed good efficacy with higher genetic barrier to resistance.
Asunto(s)
Adolescente , Adulto , Humanos , Fármacos Anti-VIH/administración & dosificación , Terapia Antirretroviral Altamente Activa/métodos , Inhibidores de la Proteasa del VIH/administración & dosificación , Esquema de Medicación , Guías como Asunto , Infecciones por VIH/tratamiento farmacológicoRESUMEN
Antiretroviral therapy has been associated with hyperlipidemia in AIDS patients. This case illustrates the classic metabolic effects associated to the HAART including protease inhibitors and/or stavudine. It was showed that the management of the HAART-associated dyslipidaemia with conventional antihyperlipidemic therapy may fail, being the switching strategy the best option.