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

ART is key to clearing oncogenic HPV genotypes (HR-HPV) in anal mucosa of HIV-positive MSM

Background: Anal squamous cell carcinoma (ASCC) is one of the most frequent non-AIDS-defining neoplasias in HIV patients, mainly in MSM, and it has been associated with chronic infection with high-risk human papilloma virus (HR-HPV). Our main objective was to determine HR-HPV clearance and acquisition rates and related factors and their relationship with the incidence of HSILs and ASCC in anal mucosa of HIV+ MSM. Patients and methods: The study included consecutive HIV-infected MSM between May 2010 and December 2018. Data were gathered at baseline and annually on their sexual behavior, CD4 and CD8 levels, plasma HIV viral load, and results of anal cytology, HPV PCR, and high-resolution anoscopy. Results: Out of the 405 patients studied, 34.9% of patients cleared oncogenic genotypes (IQR: 37-69) within 49 months, and 42.9% acquired new genotypes within 36 months (IQR:12-60). In multivariate analysis, clearance was only significantly influenced by the duration of antiretroviral therapy (ART) (OR: 1.016, 95% CI 1.003-1.030). The incidence of HSILs was 30.86/1,000 patient-years and that of ASCC was 81.22/100,000 patient-years; these incidences were not influenced by the acquisition (acquired: 14.9% vs. non-acquired: 10.4%; p = 0.238) or clearance (cleared 11.4% vs. non-cleared: 13.2%; p = 0.662) rates of these viruses. Conclusions: The duration of ART appears to positively affect oncogenic genotype clearance in the anal mucosa of HIV+ MSM, although this clearance does not affect the incidence of HSILs or ASCC. The reduction in HSIL+ rate observed in our patients may be attributable to the bundle of measures adopted at our center

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

Effect of Monotherapy with Darunavir/Ritonavir on Viral Load in Seminal Fluid, and Quality Parameters of Semen in HIV-1-Positive Patients

Patients with human immunodeficiency virus type 1 (HIV-1) who receive antiretroviral therapy (ART) often achieve increased survival and improved quality of life. In this respect, monotherapy with darunavir/ritonavir (mDRV/r) can be a useful treatment strategy. This prospective study analyses the effect of mDRV/r on sperm quality and viral load in a group of 28 patients who had previously been given conventional ART and who had recorded a viral load 20 copies/ml), and that at V1, after mDRV/r treatment, this figure had fallen to 3%. The quality of seminal fluid was close to normal in 57% of patients at V0 and in 62% at V1. We conclude that, similar to ART, mDRV/r maintains HIV-1 viral load in most patients, and that there is no worsening in seminal fluid quality

Antiretroviral therapy as a factor protective against anal dysplasia in HIV-infected males who have sex with males

Objectives: Chronic infection with oncogenic HPV genotype is associated with the development of anal dysplasia. Antiretroviral therapy (ART) has been shown to decrease the incidence of cervical carcinoma in women with HIV. We sought to: 1) describe the prevalence and grade of anal dysplasia and HPV infection in our study subjects; 2) analyze the grade of correlation between anal cytology, PCR of high-risk HPV, and histology; 3) identify the factors associated with the appearance of $AIN2 lesions. Design: Cross-sectional, prospective study. Methods: A cohort of HIV-positive males (n = 140, mean age = 37 years) who have sex with males (MSM) had epidemiological, clinical and analytical data collected. Anal mucosa samples were taken for cytology, HPV PCR genotyping, and anoscopy for histological analysis. Results: Within the cohort, 77.1situ; 74.2PCR identifying HR-HPV better predicts the histology findings than either of these factors alone. Logistic regression highlighted ART as a protective factor against$AIN2 lesions (OR: 0.214; 95%CI: 0.054–0.84). Anal/genital condylomas (OR: 4.26; 95%CI: 1.27–14.3), and HPV68 genotype (OR: 10.6; 95%CI: 1.23–91.47) were identified as risk factors. Conclusions: In our cohort, ART has a protective effect against dysplastic anal lesions. Anal/genital warts and HPV68 genotype are predictors of $AIN2 lesions. Introducing PCR HPV genotype evaluation improves screening success over that of cytology alon

Genotypic resistance in HIV-1—infected patients with persistent low-level viremia

Financiación: Consejería de Innovación, Ciencia y Empresa, Junta de Andalucia (CTS213; PO6-CTS-01498), Consejería de Salud, Junta de Andalucía (377/05; PI-0129; PI/0408/08) y Fondo de Investigación Sanitaria (PI051513, ISCIII-RETIC RD06/00006/0016).Introducción: se considera éxito terapéutico cuando un paciente con el virus de la inmunodeficiencia humana (VIH) sometido a tratamiento antirretroviral de gran actividad (TARGA) consigue una carga viral plasmática<50 copias/ml. Sin embargo, es frecuente encontrar a pacientes cuya carga viral se sitúa en 50–1.000 copias/ml, en estos casos las guías de tratamiento no recomiendan realizar un test genotípico de resistencias aduciendo una baja rentabilidad. El objetivo principal de este estudio fue examinar la utilidad de una técnica de concentración para la secuenciación de VIH-1 desde muestras que contienen menos de 1.000 copias/ml, y a partir de aquí determinar las consecuencias virológicas de los cambios guiados por el test de resistencia genotípica del TARGA de estos pacientes. Métodos: se estudió a 51 pacientes con cargas virales de 50–1.000 copias/ml, de los que 27 presentaron estos valores de carga viral durante al menos 12 meses consecutivos. Antes de la extracción del ARN, se concentró una muestra de 3 ml de plasma y, a continuación, se genotipó siguiendo el procedimiento estándar. Resultados: se pudo secuenciar 47 muestras de las 51, con una sensibilidad del 92%. De estos 47 pacientes, 27 mantienen carga viral de 50–1.000 copias/ml durante 12 meses, de ellos, 20 consiguen carga viral indetectable al cambiar el TARGA guiado por el genotipo (análisis por intención de tratar; no consta=fracaso; 20 de 27 [74,1%]) (análisis en tratamiento; 20 de 23 [86,9%]). Conclusiones: mostramos una modificación sencilla de la secuenciación genotípica en pacientes con grados de viremia persistentemente bajos, que resulta en una modificación en el régimen del TARGA que consigue una viremia plasmática indetectable.Introduction: Highly active antiretroviral therapy (HAART) in HIV patients is considered successful when plasma viral load (VL) reaches<50 copies/ml. However, many patients have a persistent VL of 50 to 1000 copies/ml, and treatment guidelines do not recommend genotypic resistance testing at these levels because of poor performance. The aim of this study was to evaluate the usefulness of a concentration technique for HIV-1 sequencing in samples with<1000 copies/ml, and determine the virological consequences of HAART treatment changes guided by resistance testing in this scenario. Methods: Observational study performed in 51 patients with plasma VL between 50 and 1000 copies/m; 27 patients had these levels for at least 12 consecutive months. Prior to RNA extraction, virions were concentrated from 3-ml plasma samples and then genotyped following standard procedures. Results: Forty-seven of the 51 samples were successfully sequenced, resulting in a sensitivity of 92%. Among these 47 patients, 27 showed a persistent viral load of 50–1000 copies/ml for 12 months, and 20 patients achieved undetectable viral load following the genotype-guided HAART change (intention-to-treat analysis: NC=F; 20 of 27 [74.1%]; on-treatment analysis: 20 of 23 [86.9%]). Conclusions: We report a simple method for genotype sequencing in patients with persistent low-level viremia that allowed a modification of the HAART regimen leading to undetectable plasma viremia.Junta de Andalucía (CTS213; PO6-CTS-01498), (377/05; PI-0129; PI/0408/08)Fondo de Investigación Sanitaria (PI051513, ISCIII-RETIC RD06/00006/0016

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