Microenvironment Eradication of Hepatitis C: A Novel Treatment Paradigm.

OBJECTIVES: Prisons are major reservoirs of hepatitis C virus (HCV) in which a therapeutic approach has been particularly difficult so far. Our aim was to create a permanent program of HCV elimination in a prison based on a "test and treat" strategy. METHODS: This open-label clinical trial was conducted in the Spanish prison "El Dueso" between May 2016 and July 2017. Viremic patients were treated with a ledipasvir-sofosbuvir regimen (8-12 weeks) according to the 2015 Spanish Guidelines. A teleconsultation program was established to follow-up patients from the hospital. Non-responders were submitted for a phylogenetic analysis and offered retreatment. An evaluation of new cases of HCV infection was performed every 6 months and upon release in all inmates. RESULTS: 847 (99.5%) inmates accepted to participate. HCV antibodies were present in 110 (13.0%) and 86 (10.2%) had detectable viremia. Most of them were genotype 1 or 3 (82.6%) and had

[P-glycoprotein and human immunodeficiency virus infection]. / Glucoproteína P e infección por el virus de la inmunodeficiencia humana.

P-glycoprotein (PGP) is a membrane protein and product of the MDR-1 gene, which acts as an efflux pump for several drugs, such as protease inhibitors (PI) used in HIV. Numerous studies in vitro, in experimental animals, and in patients have analyzed the relationships between PGP and the pharmacokinetic and pharmacodynamic properties of antiretroviral agents, with differing conclusions. In addition, studies focusing on the impact of single nucleotide polymorphisms in the MDR-1 gene, mainly C3435T in exon 26 and G2677A/G2677T in exon 21, on antiretroviral plasma concentrations, efficacy and adverse effects, have reported varying results, which have been attributed to the influence of other polymorphisms, such as cytochrome P450.

Glucoproteína P e infección por el virus de la inmunodeficiencia humana / P-glycoprotein and human immunodeficiency virus infection

La glucoproteína P (PGP) es una proteína de membrana, producto del gen MDR-1, que actúa como bomba expulsora de diversos fármacos, entre ellos los inhibidores de proteasa (IP) del virus de la inmunodeficiencia humana (VIH). Numerosos estudios in vitro, en animales y en pacientes, han analizado las relaciones de esta proteína con la farmacocinética y farmacodinamia de los antirretrovirales, con conclusiones dispares. Por otra parte, las publicaciones que analizan la influencia de los polimorfismos de nucleótido único del gen MDR-1, principalmente el C3435T en el exón 26, y el G2677A/G2677T en el exón 21, con las concentraciones plasmáticas de los antirretrovirales, su eficacia y efectos secundarios también demuestran resultados variables que se han tratado de explicar mediante la influencia de otros polimorfismos como el del citocromo p-450 (AU)

P-glycoprotein (PGP) is a membrane protein and product of the MDR-1 gene, which acts as an efflux pump for several drugs, such as protease inhibitors (PI) used in HIV. Numerous studies in vitro, in experimental animals, and in patients have analyzed the relationships between PGP and the pharmacokinetic and pharmacodynamic properties of antiretroviral agents, with differing conclusions. In addition, studies focusing on the impact of single nucleotide polymorphisms in the MDR-1 gene, mainly C3435T in exon 26 and G2677A/G2677T in exon 21, on antiretroviral plasma concentrations, efficacy and adverse effects, have reported varying results, which have been attributed to the influence of other polymorphisms, such as cytochrome P450 (AU)

Effectiveness and safety of simplification therapy with once-daily tenofovir, lamivudine, and efavirenz in HIV-1-infected patients with undetectable plasma viral load on HAART.

OBJECTIVE: To evaluate the effectiveness and tolerability of a simplification regimen with tenofovir DF (TDF), lamivudine (3TC), and efavirenz (EFV) in HAART-experienced HIV-1-infected subjects with sustained viral suppression. METHOD: Patients with HIV-1 RNA <200 copies/mL during the previous 6 months and who switched their current twice-daily or three-times-daily HAART to a simplified once-daily regimen of TDF (300 mg), 3TC (300 mg), and EFV (600 mg) were included. RESULTS: 154 patients (70% males, mean age 42 years) were included. Previous HAART included a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimen in 55% of the patients and a thymidine analog in 87%. The percentage of patients with viral load <200 copies/mL in the intent-to-treat (ITT) data set was 83% at 6 months and 75% at 12 months (98% and 96%, respectively, in the on-treatment [OT] analysis). Five patients (3%) were identified as virologic failures according to the study protocol. The mean CD4 T-cell count increased significantly 12 months after simplification (from 570 to 632 cells/mm3; p < .01). At 12 months, mean triglyceride levels decreased from 233 to 170 mg/dL (p < .01) and mean cholesterol levels decreased from 205 to 189 mg/dL (p < .01). Thirty-three patients (21%) discontinued the study treatment prior to completing the 12-month follow-up. CONCLUSION: Simplification to a once-daily regimen containing TDF, 3TC, and EFV is virologically and immunologically effective, well-tolerated, and safe with benefits in the lipid profile in the majority of patients.

[Spanish recommendations for proper use of enfuvirtide]. / Recomendaciones españolas sobre el uso adecuado de enfuvirtida.

Enfuvirtide is a high-cost, parenterally administered drug commonly used in late phases of HIV infection, when its efficacy may be compromised. To optimize enfuvirtide use, consensus recommendations for this purpose have been formulated by 247 physicians attending patients with HIV infection in Spain. A literature review was performed in which grades of evidence and recommendations were defined according to the origin of the data (randomized clinical trials, non-randomized studies, expert opinion). Twenty-eight local consensus meetings were held between May and September 2005 to discuss the most important aspects related to the use of enfuvirtide, following a pre-established system used in all the meetings. The main conclusions were as follows: a) enfuvirtide use is often excessively delayed and is given to patients with little chance of treatment success; b) enfuvirtide is indicated in patients who require antiretroviral treatment and for whom an optimum treatment with three other fully effective drugs cannot be designed; c) the most important prognostic factor is the availability of at least one other completely active drug; d) there is no infallible method to avoid the development of local reactions, but measures are available to decrease their incidence and severity; and e) patient counseling and training for correct administration of the drug are essential to improve adherence, the repercussions of local reactions and, of course, the efficacy of the treatment.

Impact of ribavirin exposure on early virological response to hepatitis C therapy in HIV-infected patients with chronic hepatitis C.

BACKGROUND: The use of pegylated interferon (PEG-IFN) plus ribavirin (RBV) is currently the recommended treatment for chronic hepatitis C virus (HCV) infection. Coinfection with HIV is a negative predictor of response, for reasons not well understood. METHODS: We examined the virological response at weeks 4 and 12 in 198 HCV/HIV-coinfected patients enrolled in a prospective trial in which PEG-IFN alpha 2a (180 microg per week) and RBV (1000-1200 mg daily) were provided. RESULTS: In an on-treatment analysis, 52.8% of patients achieved undetectable HCV-RNA (<600 IU/ml) at week 4, while 63% and 77.2% of patients had a decline of at least 2 and 1 log10, respectively. At week 12, 73.1% of patients reached undetectable HCV-RNA, and 83.5% and 89% achieved at least a 2- and 1-log10 drop, respectively. More than 85% of HCV genotypes 2/3 cleared HCV-RNA at week 4, a proportion significantly higher when compared with genotypes 1 (33.8%) and 4 (28.6%). Multivariate logistic regression analysis identified genotype 3 and RBV exposure (mg/kg of body weight) as independent predictors of virological response at week 12 of therapy. CONCLUSION: Early virological response rates to PEG-IFN plus RBV in HCV/HIV-coinfected patients seem to be similar to those reported for HCV-monoinfected subjects. The use of suboptimal doses of RBV in most earlier trials might account for the low response rates seen in coinfected patients. To our knowledge, this is the first report demonstrating that RBV exerts a significant independent effect on early virological response. Therefore, strategies aimed at optimizing doses and adherence to RBV might help to improve responses to HCV therapy in coinfected patients.

Contusión Cardíaca. Informe de 4 casos / Cardiac contusion. Report of 4 cases

Se presentaron 4 pacientes del sexo masculino (historías clínicas números 767 451, 898 039, 606 959 y 780 349), con antecedentes, hallazgos físicos y métodos diagnósticos positivos de contusión cardíaca, los cuales fueron atendidos en el Centro de Urgencias del Hospital (Instituto Superior de Medicina Militar "Luis Díaz Soto") entre el 25 de octubre de 1989 y el 12 de febrero de 1990. El paciente más joven tenía 18 años y el más viejo 64. Los 4 pacientes presentaron síntomas variables de contusión cardíaca. El dolor retroesternal fue la manifestación clínica más constante. De los métodos utilizados para el diagnóstico, las alteraciones del segmento ST y de la onda T en los electrocardiogramas y la elevación en el suero de la fracción MB de la creatina fosfoquinasa por encima del 5 por ciento fueron los elementos de mayor valor para el diagnóstico. Los indicadores pronósticos fueron de 20 en los casos 1,2 y 3 (severo sin peligro de muerte) y en el cuarto fue de 34 (severo con peligro de muerte). Todos los enfermos evolucionaron favorablemente(AU)

Contusion cardiaca: informe de 4 casos / Cardiac contusion: report of 4 cases

Se presentaron 4 pacientes del sexo masculino (historias clinicas numeros 767 451, 898 039, 606 959 y 780 349), con antecedentes, hallazgos fisicos y metodos diagnosticos positivos de contusion cardiaca, los cuales fueron atendidos en el Centro de Urgencias del Hospital (Instituto Superior de Medicina Militar "Luis Diaz Soto") entre el 25 de octubre de 1989 y el 12 de febrero de 1990. El paciente mas joven tenia 18 anos y el mas viejo 64. Los 4 pacientes presentaron sintomas variables de contusion cardiaca. El dolor retroesternal fue la manifestacion clinica mas constante. De los metodos utilizados para el diagnostico, las alteraciones del segmento ST y de la onda T en los electrocardiogramas y la elevacion en el suero de la fraccion MB de la creatina fosfoquinasa por encima del 5 por ciento fueron los elementos de mayor valor para el diagnostico. Los indicadores pronosticos fueron de 20 en los casos 1,2 y 3 (severo sin peligro de muerte) y en el cuarto fue de 34 (severo con peligro de muerte). Todos los enfermos evolucionaron favorablemente