Week 240 Efficacy and Safety of Fostemsavir Plus Optimized Background Therapy in Heavily Treatment-Experienced Adults with HIV-1.

INTRODUCTION: Efficacy and safety of the attachment inhibitor fostemsavir + optimized background therapy (OBT) were evaluated through 48 and 96 weeks in the phase 3 BRIGHTE trial in heavily treatment-experienced (HTE) adults failing their current antiretroviral regimen. Here, we report 240-week efficacy and safety of fostemsavir + OBT in adults with multidrug-resistant human immunodeficiency virus (HIV)-1 in BRIGHTE. METHODS: Heavily treatment-experienced adults failing their current regimen entered the randomized cohort (RC; 1-2 fully active antiretrovirals available) or non-randomized cohort (NRC; no fully active antiretrovirals available) and received open-label fostemsavir + OBT (starting Day 8 in RC and Day 1 in NRC). Endpoints included proportion with virologic response (HIV-1 RNA < 40 copies/mL, Snapshot), immunologic efficacy, and safety. RESULTS: At Week 240, 45% and 22% of the RC and NRC, respectively, had virologic response (Snapshot); 7% of the RC and 5% of the NRC had missing data due to coronavirus disease 2019 (COVID-19)-impacted visits. In the observed analysis, 82% of the RC and 66% of the NRC had virologic response. At Week 240, mean change from baseline in CD4+ T-cell count was 296 cells/mm3 (RC) and 240 cells/mm3 (NRC); mean CD4+/CD8+ ratio increased between Weeks 96 and 240 (RC 0.44 to 0.60; NRC 0.23 to 0.32). Between Weeks 96 and 240, four participants discontinued for adverse events, one additional participant experienced a drug-related serious adverse event, and six deaths occurred (median last available CD4+ T-cell count, 3 cells/mm3). COVID-19-related events occurred in 25 out of 371 participants; all resolved without incident. CONCLUSION: Through ~5 years, fostemsavir + OBT demonstrated durable virologic and immunologic responses with no new safety concerns between Weeks 96 and 240, supporting this regimen as a key therapeutic option for HTE people with multidrug-resistant HIV-1. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02362503.

Week 96 Genotypic and Phenotypic Results of the Fostemsavir Phase 3 BRIGHTE Study in Heavily Treatment-Experienced Adults Living with Multidrug-Resistant HIV-1.

In the phase 3 BRIGHTE study in heavily treatment-experienced adults with multidrug-resistant HIV-1, fostemsavir plus optimized background therapy (OBT) resulted in sustained rates of virologic suppression through 96 weeks. HIV-1 RNA <40 copies/mL was achieved in 163/272 (60%) Randomized Cohort (RC) participants (with 1 or 2 remaining approved fully active antiretrovirals) and 37/99 (37%) Non-randomized Cohort (NRC) participants (with 0 fully active antiretrovirals). Here we report genotypic and phenotypic analyses of HIV-1 samples from 63/272 (23%) RC participants and 49/99 (49%) NRC participants who met protocol-defined virologic failure (PDVF) criteria through Week 96. The incidence of PDVF was as expected in this difficult-to-treat patient population and, among RC participants, was comparable regardless of the presence of predefined gp120 amino acid substitutions that potentially influence phenotypic susceptibility to temsavir (S375H/I/M/N/T, M426L, M434I, M475I) or baseline temsavir 50% inhibitory concentration fold change (IC50 FC). The incidence of PDVF was lower among participants with higher overall susceptibility score to newly used antiretrovirals (OSS-new), indicating that OSS-new may be a preferred predictor of virologic outcome in heavily treatment-experienced individuals. Predefined gp120 substitutions, most commonly M426L or S375N, were emergent on treatment in 24/50 (48%) RC and 33/44 (75%) NRC participants with PDVF, with related increases in temsavir IC50 FC. In BRIGHTE, PDVF was not consistently associated with treatment-emergent genotypic or phenotypic changes in susceptibility to temsavir or to antiretrovirals in the initial OBT. Further research will be needed to identify which factors are most likely to contribute to virologic failure in this heavily treatment-experienced population (ClinicalTrials.gov, NCT02362503).

Eficacia y seguridad en condiciones clínicas reales del raltegravir en un hospital de referencia del seguro social peruano / Efficacy and safety in real clinical conditions of Raltegravir in a reference hospital of peruvian social security

INTRODUCCIÓN: El Rategravir pertenece a los inhibidores de integrasas, quedando demostrado y aprobado por diversos ensayos clínicos como un potente antirretroviral seguro y eficaz para el tratamiento de pacientes infectados con el virus de inmunodeficiencia humana (VIH), con buena tolerancia y baja toxicidad, incluyéndose en el esquema de tercera línea o rescate y se inicia cuando los esquemas de primera y segunda línea han fracasado. OBJETIVO: Evaluar la eficacia y seguridad en condiciones clínicas reales del uso de Raltegravir dentro de los esquemas de la Terapia Antiretroviral de Gran Actividad (TARGA) en pacientes con infección por VIH en un hospital de referencia del seguro social en Perú. MÉTODOS: Se realizó un estudio observacional retrospectivo en pacientes con diagnóstico de infección por VIH que iniciaron tratamiento dentro del esquema TARGA basados en Raltegravir con seguimiento y control a los 6 meses. Se presentaron medidas de resumen de frecuencias y porcentajes para las variables cualitativas, así como medias y desviación estándar para las variables cuantitativas en base a los resultados de las pruebas de normalidad. Los datos fueron procesados y analizados en el software estadístico SPSS versión 22. RESULTADOS: El género masculino fue el más afectado con un 76%(n=119) del total. El rango de edad más frecuente fue el comprendido entre los 45 a 55 años (25,4%; n=40). Las comorbilidades más frecuentes fueron Diabetes mellitus e Hipertensión arterial, con reducción exponencial de la carga viral y elevación de los niveles de linfocitos CD4. CONCLUSIÓN: El Raltegravir es eficaz para el tratamiento de pacientes VIH

INTRODUCTION: Rategravir belongs to integrase inhibitors, being demonstrated and approved by several clinical trials as a powerful and safe antiretroviral drug for the treatment of patients infected with human immunodeficiency virus (HIV), with good tolerance and low toxicity, including in the third line or rescue scheme and it starts when the first and second lineas schemes have failed. OBJECTIVE: To evaluate the efficacy and safety in real clinical conditions of the use of Raltegravir within the HAART schemes in patients with HIV infection in a reference hospital of social insurance in Peru. METHODS: A retrospective observational study was performed in patients with a diagnosis of HIV infection who started treatment within the TARGA scheme based on Raltegravir with follow-up and control at 6 months. We presented summary measures of frequencies and percentages for the qualitative variables, as well as means and standard deviation for the quantitative variables based on the results of the normality tests. The data was processed and analyzed in the statistical software SPSS version 22. RESULTS: The male gender was the most affected with 76% (n = 119) of the total. The most frequent age range was between 45 to 55 years (25.4%, n = 40). The most frequent comorbidities were Diabetes mellitus and arterial hypertension, with exponential reduction in viral load and elevation of CD4 lymphocyte levels. CONCLUSION: Raltegravir is effective for the treatment of HIV patients

Mucormicosis diseminada en un paciente diabético: un reporte de caso / Disseminated mucormycosis in a diabetic patient: a case report

La mucormicosis es una infección fúngica altamente mortal que se presenta en pacientes con algún grado de inmunosupresión, siendo la forma rinocerebral la más común. Es el primer reporte en el Perú de mucormicosis diseminada con compromiso multisistémico en un paciente con cetoacidosis diabética. Se presenta el caso de un varón de 47 años diabético procedente de la selva peruana con cuadro de insuficiencia respiratoria en ventilación mecánica. A su ingreso presenta leucocitosis, acidosis metabólica anion gap elevado, hiperglicemia e hipoalbuminemia. Posteriormente, es intervenido quirúrgicamente en tres oportunidades por presentar abdomen agudo con hallazgos en la patología de necrosis y perforación de varios órganos, falleciendo a los pocos días. Paciente se encontraba recibiendo su quinta dosis de anfotericina B deoxicolato. Se observaron hifas con angulación recta compatible con mucormicosis en estómago, intestino y pulmón.

Mucormycosis is a highly lethal fungal infection occurring in patients with some degree of immunosuppression. The rhinocerebral form is the most frequent presentation. This is the first report in Peru of a case of disseminated mucormycosis in a patient with diabetic ketoacidosis. This is a 47-year-old diabetic male subject who was referred from the Amazon jungle and presented with respiratory insufficiency receiving mechanical ventilation. On admission, the patient had leukocytosis, metabolic acidosis with high anion gap, hyperglycemia, and hypoalbuminemia. Soon afterwards, the patient underwent surgery because of acute abdomen, and the anatomopathological examination revealed necrosis and hollow viscus perforation, and he ultimately died. At this time, he was receiving amphotericin B deoxycholate. Straight angle hyphae compatible with mucormycosis were found in stomach, intestine, and lungs.

[Ceftriaxone-resistant Streptococcus pneumoniae meningitis: case report]. / Meningitis por Streptococcus pneumoniae resistente a ceftriaxona: reporte de un caso.

Infectious meningitis is a medical emergency. Within the spectrum of infectious agents, the most important is Streptococcus pneumoniae, the most frequent etiological agent of bacterial meningitis. The initiation of empirical antimicrobial treatment bears great importance and considers third-generation cephalosporins as the first alternative. However, cases of ceftriaxone resistance have been reported in several regions of the world. This has become an emerging problem in need of reconsideration of the current empirical antibiotic treatment schemes. We present the case of a 56-year old man with acute infectious meningitis caused by ceftriaxone-resistant Streptococcus pneumoniae, who responded favorably to combined empirical treatment with ceftriaxone and vancomycin and to whom, during his hospital stay, the presence of hypothyroidism and mega cisterna magna was diagnosed.

La meningitis infecciosa es una emergencia médica. Dentro del espectro de agentes infecciosos, el más importante es el Streptococcus pneumoniae, agente etiológico más frecuente de la meningitis bacteriana. El inicio de tratamiento antimicrobiano empírico es de gran importancia y considera a las cefalosporinas de tercera generación como la primera alternativa. Sin embargo, casos de resistencia a ceftriaxona han sido reportados en diversas partes del mundo, siendo un problema emergente, por lo que necesita una reconsideración de los esquemas antibióticos empíricos actuales. Presentamos el caso de un varón de 56 años que presenta meningitis aguda infecciosa por Streptococcus pneumoniae resistente a ceftriaxona, que respondió favorablemente al tratamiento empírico combinado con ceftriaxona y vancomicina y que durante su estadía hospitalaria se detectó la presencia de hipotiroidismo y megacisterna magna.

Meningitis por Streptococcus pneumoniae resistente a ceftriaxona: reporte de un caso / Ceftriaxone-resistant Streptococcus pneumoniae meningitis: case report

RESUMEN La meningitis infecciosa es una emergencia médica. Dentro del espectro de agentes infecciosos, el más importante es el Streptococcus pneumoniae, agente etiológico más frecuente de la meningitis bacteriana. El inicio de tratamiento antimicrobiano empírico es de gran importancia y considera a las cefalosporinas de tercera generación como la primera alternativa. Sin embargo, casos de resistencia a ceftriaxona han sido reportados en diversas partes del mundo, siendo un problema emergente, por lo que necesita una reconsideración de los esquemas antibióticos empíricos actuales. Presentamos el caso de un varón de 56 años que presenta meningitis aguda infecciosa por Streptococcus pneumoniae resistente a ceftriaxona, que respondió favorablemente al tratamiento empírico combinado con ceftriaxona y vancomicina y que durante su estadía hospitalaria se detectó la presencia de hipotiroidismo y megacisterna magna.

ABSTRACT Infectious meningitis is a medical emergency. Within the spectrum of infectious agents, the most important is Streptococcus pneumoniae, the most frequent etiological agent of bacterial meningitis. The initiation of empirical antimicrobial treatment bears great importance and considers third-generation cephalosporins as the first alternative. However, cases of ceftriaxone resistance have been reported in several regions of the world. This has become an emerging problem in need of reconsideration of the current empirical antibiotic treatment schemes. We present the case of a 56-year old man with acute infectious meningitis caused by ceftriaxone-resistant Streptococcus pneumoniae, who responded favorably to combined empirical treatment with ceftriaxone and vancomycin and to whom, during his hospital stay, the presence of hypothyroidism and mega cisterna magna was diagnosed.

Loxoscelismo escrotal / Scrotal loxoscelism

Loxoscelismo es el cuadro clínico originado por la mordedura de araña del género Loxosceles. Es considerado un accidente que ocurre con mayor frecuencia en las noches, debido al hábito nocturno de la araña y buena adaptación a los ambientes domésticos, preferentemente en espacios oscuros y secos. Clínicamente presenta dos escenarios, cutáneo (83,3 %) y visceral o sistémico (16 %), con una variación del cuadro cutáneo denominado loxoscelismo predominantemente edematoso. El objetivo es informar un caso inusual de loxoscelismo escrotal. El diagnóstico se realizó mediante las características clínicas y epidemiológicas del accidente. En conclusión, el loxoscelismo escrotal es una entidad muy infrecuente, el manejo del paciente influye mucho en su evolución y progresión; el tratamiento exhaustivo con sulfadiazina 2 veces al día y antibióticos intravenosos, muestra resultados muy favorables.

Loxoscelism is a condition produced by the bite of spiders from the genus Loxosceles. It is considered to be an accident that occurs mostly in the night, due to the spider's nocturnal habits and good adaptation to domestic environments, preferably dark, dry spaces. It presents in two clinical scenarios: cutaneous (83.3 %) and visceral or systemic (16 %), with a variation in the cutaneous manifestation known as predominantly edematous loxoscelism. The objective of the study was to report an unusual case of scrotal loxoscelism. Diagnosis was based on the clinical and epidemiological characteristics of the accident. It is concluded that scrotal loxoscelism is a very infrequent condition. Management of the patient greatly influences its evolution and progress. Exhaustive treatment with sulfadiazine twice daily and intravenous antibiotics yields very favorable results.

Infective endocarditis due to Bartonella bacilliformis associated with systemic vasculitis: a case report.

Infective endocarditis due to Bartonella bacilliformis is rare. A 64-year-old woman, without previous heart disease, presented with 6 weeks of fever, myalgias, and arthralgias. A systolic murmur was heard on the tricuspid area upon examination, and an echocardiogram showed endocardial lesions in the right atrium. Bartonella bacilliformis was isolated in blood cultures, defining the diagnosis of infective endocarditis using Duke's criteria. Subsequently, the patient developed clinical and laboratory features compatible with antineutrophil cytoplasmic antibody-associated vasculitis. This case presents an uncommon complication of B. bacilliformis infection associated with the development of systemic vasculitis.

Infective endocarditis due to Bartonella bacilliformis associated with systemic vasculitis: a case report

Abstract Infective endocarditis due to Bartonella bacilliformis is rare. A 64-year-old woman, without previous heart disease, presented with 6 weeks of fever, myalgias, and arthralgias. A systolic murmur was heard on the tricuspid area upon examination, and an echocardiogram showed endocardial lesions in the right atrium. Bartonella bacilliformis was isolated in blood cultures, defining the diagnosis of infective endocarditis using Duke's criteria. Subsequently, the patient developed clinical and laboratory features compatible with antineutrophil cytoplasmic antibody-associated vasculitis. This case presents an uncommon complication of B. bacilliformis infection associated with the development of systemic vasculitis.

Safety and efficacy of the HIV-1 attachment inhibitor prodrug BMS-663068 in treatment-experienced individuals: 24 week results of AI438011, a phase 2b, randomised controlled trial.

BACKGROUND: BMS-663068 is an oral prodrug of BMS-626529, an attachment inhibitor that binds to HIV-1 gp120, blocking viral attachment to host CD4 cells. AI438011 is an ongoing trial investigating the efficacy, safety, and dose-response of BMS-663068 in treatment-experienced, HIV-1-infected patients. Herein we present the results of the primary analysis. METHODS: AI438011 is a phase 2b, randomised, active-controlled trial, at 53 hospitals and outpatient clinics across ten countries in North and South America, Europe, and Africa. Individuals with an HIV-1 RNA viral load of at least 1000 copies per mL and a BMS-626529 half-maximum inhibitory concentration lower than 100 nmol/L were randomly assigned (1:1:1:1:1) to receive either BMS-663068 at 400 mg twice daily, 800 mg twice daily, 600 mg once daily, or 1200 mg once daily or ritonavir-boosted atazanavir (300 mg of atazanavir and 100 mg of ritonavir once daily), each with 400 mg of raltegravir twice daily and 300 mg of tenofovir disoproxil fumarate once daily as a backbone. The sponsor, participants, and investigators were masked for BMS-663068 dose but not for allocation. Primary endpoints were the proportion of patients with an HIV-1 RNA viral load less than 50 copies per mL (response rate) at week 24 and the frequency of serious adverse events and adverse events leading to discontinuation, up to the week 24 analysis. The primary analyses included all patients who received at least one dose of study drug (modified intention-to-treat population). This study is registered at ClinicalTrials.gov, NCT01384734. FINDINGS: Between July 26, 2011, and July 16, 2012, 581 participants were assessed for eligibility. Of these, 254 patients were randomly assigned to receive either BMS-663068 (n=52 for the 400 mg twice daily group, n=50 for the 800 mg twice daily group, n=51 for the 600 mg once daily group, and n=50 for the 1200 mg once daily group) or ritonavir-boosted atazanavir (n=51). 200 patients received at least one dose of BMS-663068, and 51 patients received at least one dose of ritonavir-boosted atazanavir. At week 24, 40 (80%) of 50 patients in the BMS-663068 400 mg twice daily group, 34 (69%) of 49 patients in the 800 mg twice daily group, 39 (76%) of 51 patients in the 600 mg once daily group, and 36 (72%) of 50 patients in the 1200 mg once daily group had an HIV-1 RNA viral load less than 50 copies per mL, compared with 38 (75%) of 51 patients in the ritonavir-boosted atazanavir group. Serious adverse events were noted in 13 (7%) of 200 patients in the BMS-663068 groups and five (10%) of the 51 patients in the ritonavir-boosted atazanavir group. Four (2%) of the 200 patients in the BMS-663068 groups and two (4%) of the 51 patients in the ritonavir-boosted atazanavir group discontinued because of adverse events. No serious adverse events or adverse events leading to discontinuation were BMS-663068-related. Grade 2-4 adverse events related to study drug(s) occurred in 17 (9%) of 200 patients across the BMS-663068 groups and 14 (27%) of 51 patients in the ritonavir-boosted atazanavir group. For the BMS-663068 groups these events were mostly single instances with no dose relation and for the ritonavir-boosted atazanavir group these were mostly gastrointestinal or hepatobiliary disorders associated with hyperbilirubinaemia. INTERPRETATION: In a comparison with ritonavir-boosted atazanavir, efficacy and safety of BMS-663068 up to the week 24 analysis support continued development of BMS-663068, which is being assessed in a phase 3 trial in heavily treatment-experienced individuals. FUNDING: Bristol-Myers Squibb.

Cardiovascular disease in human immunodeficiency virus-infection as a cause of hospitalization: a case-series in a General Hospital in Peru.

BACKGROUND: Cardiovascular disease in the context of human immunodeficiency virus infection has become a major clinical concern in recent years. In the current report we assess hospitalizations due to cardiovascular disease in human immunodeficiency virus patients in a Social Security reference hospital in Peru. METHODS: A retrospective study was carried out between January 1996 and December 2012 in a General Hospital in Lima, Peru. RESULTS: We included 26 patients hospitalized due to cardiovascular disease. Mean age was 46.3 years (SD 12.5), predominantly male (57.7%). Ten patients (38.4%) were in Acquired Immunodeficiency Syndrome stages. Seventeen (65.4%) received high-active-antiretroviral therapy. Eleven (42.3%) had cardiac involvement and 15 (57.7%) had non-cardiac vascular involvement. The most frequent causes of cardiac involvement were pericardial effusion and myocardial infarction. On the other hand, deep vein thrombosis and stroke were the most frequent for non-cardiac vascular involvement. CONCLUSIONS: Cardiovascular disease is an important cause of hospitalization in Peruvian human immunodeficiency virus patients, with differences between immunosuppression stages. Further studies analyzing associated factors are warranted.

Pancreatitis por citomegalovirus en inmunocomprometidos. Reporte de casos / Cytomegalovirus pancreatitis in inmunocompromised patients: a case report

Se reporta dos casos de pancreatitis secundaria a la infección por citomegalovirus confirmado por reacción en cadena de la polimerasa en tiempo real (PCR-RT) en pacientes portadores del virus de la inmunodeficiencia humana (VIH). Se descartaron otras causas mediante exámenes auxiliares. Ambos pacientes fueron tratados con ganciclovir y se obtuvo una mejoría tanto clínica como en los exámenes auxiliares. Esta patología no debe pasar desapercibida en pacientes VIH positivos a pesar de no presentar la característica clínica de pancreatitis aguda.

Prevalencia de factores de riesgo cardiovascular en una población peruana de pacientes con infección por el virus de inmunodeficiencia humana en terapia antiretroviral de gran actividad / Prevalence of cardiovascular risk factors in Peruvian patients with HIV infections in HAART

Objetivo: Determinar la prevalencia de los factores de riesgo cardiovascular en una cohorte de pacientes con infección por el VIH que recibían terapia antiretroviral de gran actividad (TARGA). Material y métodos: Llevamos a cabo un estudio prospectivo observacional entre los meses de enero a abril del 2006 en pacientes que acudían a consulta ambulatoria del Hospital Rebagliati-ESSALUD-Perú. Resultados: En 276 pacientes encontramos una prevalencia de factores de riesgo cardiovascular como sigue: hipertensión en 3,26 por ciento, diabetes mellitus en 1,81 por ciento, dislipidemia en 34,05 por ciento, tabaquismo en 3,96 por ciento, y obesidad en 4,71 por ciento. Solo se encontró niveles mayores de colesterol total y triglicéridos en el grupo que recibía inhibidores de proteasa (p<0,05). El 4,16 por ciento de esta población tuvo una puntuación de riesgo cardiovascular elevada de acuerdo a la puntuación de Framinghan. Conclusiones: La prevalencia de factores de riesgo cardiovascular en nuestra cohorte fue baja con excepción de la prevalencia de dislipidemia, encontrándose diferencias estadísticamente significativas en la subpoblación de pacientes que recibían inhibidores de proteasa los cuales tuvieron niveles mayores de colesterol total y triglicéridos.(Rev Med Hered 2007;18:10-14).

Perfil clínico de los pacientes VIH hospitalizados en la era HAART / Clinical profile of patients VIH hospitalized in era HAART

Para evaluar las hospitalizaciones de los pacientes infectados por el VIH en la era de la Terapia antirretroviral de gran actividad, se analizaron 507 admisiones de 288 pacientes infectados por el VIH ocurridos desde el 01 de Enero de 1999 al 30 de junio del 2003 en el Hospital Edgardo Rebagliati Martins, Lima-Perú. Los pacientes tuvieron como edad promedio 41, 69 años y fueron generalmente varones heterosexuales. La mitad de las hospitalizaciones tuvieron un CD4<200 y el motivo de ingreso mas frecuente fue por causa respiratoria. Nuestros datos indican una persistente disminución de las hospitalizaciones desde 1999 hasta el primer semestre del año 2003, en los pacientes que no reciben TARGA. La reacción adversa medicamentosa a la terapia a pasado a ser el diagnóstico mas frecuente de admisión hospitalaria en pacientes que reciben TARGA. Los diferentes patrones de hospitalización pueden tener implicancias en el tratamiento futuro de los pacientes con infección por el VIH.