Effectiveness of ritonavir-boosted protease inhibitor monotherapy in clinical practice even with previous virological failures to protease inhibitor-based regimens

López-Cortés, Luis F. et al.[Background and Objective] Significant controversy still exists about ritonavir-boosted protease inhibitor monotherapy (mtPI/rtv) as a simplification strategy that is used up to now to treat patients that have not experienced previous virological failure (VF) while on protease inhibitor (PI)-based regimens. We have evaluated the effectiveness of two mtPI/rtv regimens in an actual clinical practice setting, including patients that had experienced previous VF with PI-based regimens. [Methods] This retrospective study analyzed 1060 HIV-infected patients with undetectable viremia that were switched to lopinavir/ritonavir or darunavir/ritonavir monotherapy. In cases in which the patient had previously experienced VF while on a PI-based regimen, the lack of major HIV protease resistance mutations to lopinavir or darunavir, respectively, was mandatory. The primary endpoint of this study was the percentage of participants with virological suppression after 96 weeks according to intention-to-treat analysis (non-complete/missing = failure). [Results] A total of 1060 patients were analyzed, including 205 with previous VF while on PI-based regimens, 90 of whom were on complex therapies due to extensive resistance. The rates of treatment effectiveness (intention-to-treat analysis) and virological efficacy (on-treatment analysis) at week 96 were 79.3% (CI, 76.8-81.8) and 91.5% (CI, 89.6-93.4), respectively. No relationships were found between VF and earlier VF while on PI-based regimens, the presence of major or minor protease resistance mutations, the previous time on viral suppression, CD4+ T-cell nadir, and HCV-coinfection. Genotypic resistance tests were available in 49 out of the 74 patients with VFs and only four patients presented new major protease resistance mutations. [Conclusion] Switching to mtPI/rtv achieves sustained virological control in most patients, even in those with previous VF on PI-based regimens as long as no major resistance mutations are present for the administered drug.All of the authors are members of the Sociedad Andaluza de Enfermedades Infecciosas (Andalusian Society of Infectious Diseases. http://www.saei.org/), which is the sponsor of this study.Peer Reviewe

Risk factors for ≥high-grade anal intraepithelial lesions in MSM living with HIV and the response to topical and surgical treatments

The authors are grateful to MercedesA ´ lvarez Romero for coordinating patients and drawing blood samples and to Marina Gutie´rrez and Rodrigo Lo´pez of the Pathology Department for processing samples. The authors are grateful to the participating patients.Background The objective of this study in MSM living with HIV was to determine the incidence of HSIL and ASCC, related factors, and the response to treatment. Patients and methods Data were gathered in 405 consecutive HIV-infected MSM (May 2010-December 2018) at baseline and annually on: sexual behavior, anal cytology, and HPV PCR and/or high-resolution anoscopy results. They could choose mucosectomy with electric scalpel (from May 2010) or self-administration of 5% imiquimod 3 times weekly for 16 weeks (from November 2013). A multivariate logistic regression model was developed for ≥HSIL-related factors using a step-wise approach to select variables, with a significance level of 0.05 for entry and 0.10 for exit, applying the Hosmer-Lemeshow test to assess the goodness of fit. Results The study included 405 patients with a mean age of 36.2 years; 56.7% had bachelor´s degree, and 52.8% were smokers. They had a mean of 1 (IQR 1–7) sexual partner in the previous 12 months, median time since HIV diagnosis of 2 years, and mean CD4 nadir of 367.9 cells/uL; 86.7% were receiving ART, the mean CD4 level was 689.6 cells/uL, mean CD4/CD8 ratio was 0.77, and 85.9% of patients were undetectable. Incidence rates were 30.86/1,000 patient-years for ≥high squamous intraepithelial lesion (HSIL) and 81.22/100,000 for anal squamous cell carcinoma (ASCC). The ≥HSIL incidence significantly decreased from 42.9% (9/21) in 2010 to 4.1% (10/254) in 2018 (p = 0.034). ≥HSIL risk factors were infection with HPV 11 (OR 3.81; 95%CI 1.76–8.24), HPV 16 (OR 2.69, 95%CI 1.22–5.99), HPV 18 (OR 2.73, 95%CI 1.01–7.36), HPV 53 (OR 2.97, 95%CI 1.002–8.79); HPV 61 (OR 11.88, 95%CI 3.67–38.53); HPV 68 (OR 2.44, CI 95% 1.03–5.8); low CD4 nadir (OR1.002; 95%CI 1–1.004) and history of AIDS (OR 2.373, CI 95% 1.009–5.577). Among HSIL-positive patients, the response rate was higher after imiquimod than after surgical excision (96.7% vs 73.3%, p = 0.009) and there were fewer re-treatments (2.7% vs 23.4%, p = 0.02) and adverse events (2.7% vs 100%, p = 0.046); none developed ASCC. Conclusions HSIL screening and treatment programs reduce the incidence of HSIL, which is related to chronic HPV infection and poor immunological status. Self-administration of 5% imiquimod as first-line treatment of HSIL is more effective than surgery in HIV+ MSM

Incidence of nephrotoxicity associated with intravenous colistimethate sodium administration for the treatment of multidrug‑resistant gram‑negative bacterial infections

Colistimethate sodium (CMS) is the inactive prodrug of colistin, CMS has a narrow antibacterial spectrum with concentration-dependent bactericidal activity against multidrug-resistant gramnegative bacteria, including Pseudomonas aeruginosa and Acinetobacter baumannii. This study aimed to analyze potential correlations between clinical features and the development of CMS-induced nephrotoxicity. This retrospective cohort study was conducted in a tertiary-care university hospital between 1 January 2015 and 31 December 2019. A total of 163 patients received CMS therapy. 75 patients (46%) developed nephrotoxicity attributable to colistin treatment, although only 14 patients (8.6%) discontinued treatment for this reason. 95.7% of CMS were prescribed as target therapy. Acinetobacter baumannii spp. was the most commonly identified pathogen (72.4%) followed by P. aeruginosa (19.6%). Several risk factors associated with nephrotoxicity were identified, among these were age (HR 1.033, 95%CI 1.016–1.052, p < 0.001), Charlson Index (HR 1.158, 95%CI 1.0462– 1.283; p = 0.005) and baseline creatinine level (HR 1.273, 95%CI 1.071–1.514, p = 0.006). In terms of in-hospital mortality, risk factors were age (HR 2.43, 95%CI 1.021–1.065, p < 0.001); Charlson Index (HR 1.274, 95%CI 1.116–1.454, p = 0.043), higher baseline creatinine levels (HR 1.391, 95%CI 1.084– 1.785, p = 0.010) and nephrotoxicity due to CMS treatment (HR 5.383, 95%CI 3.126–9.276, p < 0.001). In-hospital mortality rate were higher in patients with nephrotoxicity (log rank test p < 0.001). In conclusion, the nephrotoxicity was reported in almost half of the patients. Its complex management, continuous renal dose adjustment and monitoring creatinine levels at least every 48 h leads to a high percentage of inappropriate use and treatment failure

Effect of monotherapy with darunavir/ cobicistat on viral load and semen quality of HIV-1 patients

Many patients previously using darunavir/ritonavir (DRV/r) (800/100mg) have switched to darunavir/cobicistat (DRV/C) (800/150 mg) either as part of triple therapy (ART) or as monotherapy with DRV (mDRV). The latter approach continues to be used in some countries for patients receiving long-term treatment. However, to date, the behaviour of DRV/C in the seminal compartment has not been analysed. This study explores how the combination behaves in monotherapy, with respect to the control of viral load and seminal quality. To this end, we studied 20 patients who were treated with mDRV/C after previous treatment with mDRV/r for at least 24 weeks. A viral load control in seminal plasma similar to that published in the literature was observed after 24 weeks of treatment with mDRV/C (viral load positivity in 20% of patients). Similarly, semen quality was confirmed (70% normozoospermic) in patients treated with this formulation, as has previously been reported for ART and mDRV/r. The DRV levels measured in seminal plasma were above EC50, regardless of whether the seminal viral load was positive or negative. We conclude that this mDRV/C co-formulation behaves like mDRV/r in seminal plasma in terms of viral load control and semen quality

Modifications of hepatic fibrosis assessed by transient elastometry in patients with sustained virological response after treatment of hepatitis C in monoinfected (VHC) and coinfected patients(VHC – VIH)

Introducción: Se ha observado que los pacientes infectados por el virus de la hepatitis C (VHC), que ya han desarrollado un grado de fibrosis significativo, son capaces de disminuir ese grado de fibrosis, al alcanzar una respuesta viral sostenida (RVS) tras el tratamiento con interferón pegilado (PEG-IFN) y ribavirina (RBV). Objetivo: Evaluar la modificación de la fibrosis, medida por elastometría transitoria, al erradicar el VHC tanto en pacientes tratados con PEG-IFN y RBV, con Boceprevir/Telaprevir, como con agentes de acción directa (AAD) y determinar la asociación entre la variación de la fibrosis y el grado de fibrosis previo al tratamiento tanto en pacientes monoinfectados (VHC), como en coinfectados (VIH/VHC). Métodos: Estudio observacional prospectivo, en el que se estudiaron 50 pacientes y se evaluó su grado de fibrosis previo y posterior al tratamiento. Resultados: De los 62 pacientes, un 45,2% disminuyeron su fibrosis, con una media de descenso de 9,45kPa y un 45,2% disminuyeron al menos un estadio en la escala Metavir. Se observó una asociación entre un menor grado de fibrosis previo al tratamiento y un mayor descenso de la misma (p<0,001). Sin embargo no se observaron diferencias (p=0,713) entre la monoinfección y la coinfección con VIH; tampoco se detectó asociación significativa, entre los tres tipos de tratamientos y la modificación de la fibrosis (p=0,445). Conclusiones:En nuestro estudio, la consecución de la RVS en los pacientes con hepatitis crónica por VHC facilita la reducción de la fibrosis producida por la enfermedad, tanto en pacientes monoinfectados, como en coinfectados (VIH/VHC), independientemente del tratamiento usado.Introduction: It has been shown that patients infected with hepatitis C virus (HCV), who have already developed a significant degree of fibrosis, are able to reduce that degree of fibrosis by achieving a sustained virological response (SVR) after treatment with Pegylated interferon (PEG-IFN) and ribavirin (RBV). Objective: To evaluate the modification of fibrosis, measured by transient elastometry, after HCV eradication in patients treated with PEG-IFN and RBV, with Boceprevir / Telaprevir, and with direct acting agents (AAD) and to determine the association between the variation in fibrosis and the degree of pre-treatment fibrosis in both monoinfected (HCV) and coinfected (HIV / HCV) patients. Methods: This work is a prospective observational study. 50 patients were studied and their degree of fibrosis before and after treatment was evaluated. Results: 45.2% of patients decreased their fibrosis, with a mean decrease of 9.45kPa and 45.2% decreased at least one stage on the Metavir scale. There was an association between a lower degree of fibrosis before treatment and a greater decrease in fibrosis (p <0.001). However, no differences were observed between monoinfection and HIV coinfection (p = 0.713). No significant association was detected between the three types of treatments and the modification of fibrosis (p = 0.445). Conclusions: In our study, SVR in patients with chronic HCV hepatitis facilitates the reduction of fibrosis produced by the disease, both in monoinfected patients and in coinfected patients (HIV / HCV), regardless of the treatment used

Visceral leishmaniasis caused by Leishmania infantum in a Spanish patient in Argentina: What is the origin of the infection? Case report

BACKGROUND: The question "Where have you been?" is a common one asked by doctors in Northern Europe and America when faced with clinical symptoms not typical of their country. This question must also arise in the clinics of developing countries in which non-autochthonous cases such as the one described here can appear. Important outbreaks of Leishmania infantum have been recorded in the last decade in several Latin American countries but its presence has not yet been recorded in Argentina. We report the first case of visceral leishmaniasis owing to L. infantum in this country. CASE PRESENTATION: A 71-year-old Spanish woman who has been living in Mendoza, Argentina, during the last 40 years presented with a history of high fever and shivering, anemia, leukopenia and splenomegaly over two years. Argentinian doctors did not suspect visceral leishmaniasis even when the histological analysis revealed the presence of "intracytoplasmatic spheroid particles compatible with fungal or parasitic infection". After a serious deterioration in her health, she was taken to Spain where she was evaluated and visceral leishmaniasis was established. Specific identification of the parasite was done by PCR-ELISA, isoenzyme electrophoresis and RAPD-PCR. CONCLUSION: We would like to point out that: i) cases such as the one described here, which appear in non-endemic areas, can pass unnoticed by the clinical physician. ii) in countries in which these introduced cases reside, in-depth parasitological studies are required into vectors and possible reservoirs to rule out the rare case of local infection and, once infection has taken place, to ensure that this does not spread by anthroponotic transmission or a competent reservoir

Eficacia y seguridad de la simplificación del tratamiento antirretroviral en la infección VIH

La población infectada por el VIH tiene todavía un riesgo incrementado de morbimortalidad y de envejecimiento prematuro, quizás relacionado en parte con la inflamación crónica residual que subyace en toda infección VIH, pero también por el potencial tóxico a largo plazo de los ARVs, sobre todo de los AN. El máximo control de esa inflamación que puede conseguirse con el TAR se logra cuando se consigue una supresión viral por debajo de 200 ó 400 copias de RNA-VIH/mL, independientemente del número de ARVs con el que esto se consiga. Por tanto, conseguido este grado de supresión virológica (que se obtiene con cualquier propuesta actual de TAR) nuestro principal objetivo asistencial, pensando en el control a largo plazo de nuestros pacientes, debería ser la reducción del potencial tóxico del TAR. Actualmente disponemos de múltiples explicaciones que justifican la prescripción de TT, cada vez más eficaz, segura y confortable. Pero en casi ningún caso podemos afirmar que la TT es una necesidad para nuestros pacientes, que han de tomar necesariamente 2 AN el resto de sus vidas. La ciencia ha desplegado múltiples alternativas de la TT, muchas de ellas extraordinariamente sólidas (equivalentes a la TT con grado de evidencia máximo, A1) que hacen ya innecesario el mantenimiento casi universal de la Triple terapia…eterna. Por tanto, la demostración de que los tratamientos que se configuran sin la pareja de AN y en torno a los IP potenciados y los últimos II (TLA, TL de la pareja de AN) son seguros y eficaces en el mantenimiento de la supresión viral, nos ofrece una gran oportunidad para abordar la prevención y minimización de ese exceso de morbimortalidad. También para la reducción de los gastos del TAR. La ciencia nos ofrece una oportunidad para mejorar los cuidados a largo plazo de nuestros pacientes, y sólo nos queda adquirir la conciencia que nos permita asumir la importancia que esto tiene y la posibilidad de hacerlo operativo.Tesis Univ. Granada

Eficacia y seguridad de la simplificación del tratamiento antirretroviral en la infección VIH

La población infectada por el VIH tiene todavía un riesgo incrementado de morbimortalidad y de envejecimiento prematuro, quizás relacionado en parte con la inflamación crónica residual que subyace en toda infección VIH, pero también por el potencial tóxico a largo plazo de los ARVs, sobre todo de los AN. El máximo control de esa inflamación que puede conseguirse con el TAR se logra cuando se consigue una supresión viral por debajo de 200 ó 400 copias de RNA-VIH/mL, independientemente del número de ARVs con el que esto se consiga. Por tanto, conseguido este grado de supresión virológica (que se obtiene con cualquier propuesta actual de TAR) nuestro principal objetivo asistencial, pensando en el control a largo plazo de nuestros pacientes, debería ser la reducción del potencial tóxico del TAR. Actualmente disponemos de múltiples explicaciones que justifican la prescripción de TT, cada vez más eficaz, segura y confortable. Pero en casi ningún caso podemos afirmar que la TT es una necesidad para nuestros pacientes, que han de tomar necesariamente 2 AN el resto de sus vidas. La ciencia ha desplegado múltiples alternativas de la TT, muchas de ellas extraordinariamente sólidas (equivalentes a la TT con grado de evidencia máximo, A1) que hacen ya innecesario el mantenimiento casi universal de la Triple terapia…eterna. Por tanto, la demostración de que los tratamientos que se configuran sin la pareja de AN y en torno a los IP potenciados y los últimos II (TLA, TL de la pareja de AN) son seguros y eficaces en el mantenimiento de la supresión viral, nos ofrece una gran oportunidad para abordar la prevención y minimización de ese exceso de morbimortalidad. También para la reducción de los gastos del TAR. La ciencia nos ofrece una oportunidad para mejorar los cuidados a largo plazo de nuestros pacientes, y sólo nos queda adquirir la conciencia que nos permita asumir la importancia que esto tiene y la posibilidad de hacerlo operativo.Tesis Univ. Granada

Visceral leishmaniasis caused by Leishmania infantum in a Spanish patient in Argentina: What is the origin of the infection? Case report

Fil: Martín-Sánchez, Joaquina. Universidad de Granada. Departamento de Parasitología; España.Fil: Navarro-Mari, José M. Hospital Universitario Virgen de las Nieves. Servicio de Microbiología; España.Fil: Pasquau-Liaño, Juan. Hospital Universitario Virgen de las Nieves. Unidad de Enfermedades Infecciosas; Argentina.Fil: Salomón, Oscar Daniel. ANLIS Dr.C.G.Malbrán. Centro Nacional de Diagnóstico e Investigación en Endemo-Epidemias; Argentina.Fil: Morillas-Márquez, Francisco. Universidad de Granada. Departamento de Parasitología; España.Background The question "Where have you been?" is a common one asked by doctors in Northern Europe and America when faced with clinical symptoms not typical of their country. This question must also arise in the clinics of developing countries in which non-autochthonous cases such as the one described here can appear. Important outbreaks of Leishmania infantum have been recorded in the last decade in several Latin American countries but its presence has not yet been recorded in Argentina. We report the first case of visceral leishmaniasis owing to L. infantum in this country. Case presentation A 71-year-old Spanish woman who has been living in Mendoza, Argentina, during the last 40 years presented with a history of high fever and shivering, anemia, leukopenia and splenomegaly over two years. Argentinian doctors did not suspect visceral leishmaniasis even when the histological analysis revealed the presence of "intracytoplasmatic spheroid particles compatible with fungal or parasitic infection". After a serious deterioration in her health, she was taken to Spain where she was evaluated and visceral leishmaniasis was established. Specific identification of the parasite was done by PCR-ELISA, isoenzyme electrophoresis and RAPD-PCR. Conclusion We would like to point out that: i) cases such as the one described here, which appear in non-endemic areas, can pass unnoticed by the clinical physician. ii) in countries in which these introduced cases reside, in-depth parasitological studies are required into vectors and possible reservoirs to rule out the rare case of local infection and, once infection has taken place, to ensure that this does not spread by anthroponotic transmission or a competent reservoir