Incidence of sexually transmitted infections and screening models among pre-exposure prophylaxis users.

INTRODUCTION: There is discussion about the frequency of STI screening among pre-exposure prophylaxis (PrEP) users. The aim of this study was to analyse the incidence of STIs and to evaluate different screening models in order to optimise the follow-up. METHODOLOGY: A prospective study was conducted between 2017 and 2023, including 138 PrEP users in a STI clinic. Participants were tested for STIs every three months. Unscheduled visits were performed for those with STI-related symptoms or for people who were notified for an STI by a sexual partner. We performed a survival analysis of repeated events, estimating the cumulative incidence (CI) and incidence rate (IR). RESULTS: The overall CI by quarterly screening was 8.3 (95% CI: 7.6-9.1) infections per person over six years, with a decreasing trend. The most frequently diagnosed pathogen was Neisseria gonorrhoeae, with a IR of 0.76 (95% CI: 0.68-0.84). If the frequency of screening is reduced to every six months, the IR of STIs is reduced by (95% CI: 0.5-0.66) infections per user per year, and at 12 months by 0.82 (95% CI: 0.73-0.89). In the case of no pharyngeal or urethral screening, IR is reduced by 0.37 (95% CI: 0.32-0.42) infections per person per year and in those over 35 years of age by 0.33 (95% CI: 0.25-0.4). Eliminating unscheduled visits, the reduction in IR is 0.33 (95% CI: 0.24-0.42). CONCLUSIONS: The incidence of STIs among PrEP users is high, especially in the rectum, but it does not increase over time. STI screening could be optimised reducing the frequency of pharyngeal and urethral testing, particularly in those over 35 years of age. It is essential to redistribute health resources for unscheduled visits, which have been shown to be the most cost-effective screening.

Effect of EARLY administration of DEXamethasone in patients with COVID-19 pneumonia without acute hypoxemic respiratory failure and risk of development of acute respiratory distress syndrome (EARLY-DEX COVID-19): study protocol for a randomized controlled trial.

BACKGROUND: Corticosteroids are one of the few drugs that have shown a reduction in mortality in coronavirus disease 2019 (COVID-19). In the RECOVERY trial, the use of dexamethasone reduced 28-day mortality compared to standard care in hospitalized patients with suspected or confirmed COVID-19 requiring supplemental oxygen or invasive mechanical ventilation. Evidence has shown that 30% of COVID-19 patients with mild symptoms at presentation will progress to acute respiratory distress syndrome (ARDS), particularly patients in whom laboratory inflammatory biomarkers associated with COVID-19 disease progression are detected. We postulated that dexamethasone treatment in hospitalized patients with COVID-19 pneumonia without additional oxygen requirements and at risk of progressing to severe disease might lead to a decrease in the development of ARDS and thereby reduce death. METHODS/DESIGN: This is a multicenter, randomized, controlled, parallel, open-label trial testing dexamethasone in 252 adult patients with COVID-19 pneumonia who do not require supplementary oxygen on admission but are at risk factors for the development of ARDS. Risk for the development of ARDS is defined as levels of lactate dehydrogenase > 245 U/L, C-reactive protein > 100 mg/L, and lymphocyte count of < 0.80 × 109/L. Eligible patients will be randomly assigned to receive either dexamethasone or standard of care. Patients in the dexamethasone group will receive a dose of 6 mg once daily during 7 days. The primary outcome is a composite of the development of moderate or more severe ARDS and all-cause mortality during the 30-day period following enrolment. DISCUSSION: If our hypothesis is correct, the results of this study will provide additional insights into the management and progression of this specific subpopulation of patients with COVID-19 pneumonia without additional oxygen requirements and at risk of progressing to severe disease. TRIAL REGISTRATION: ClinicalTrials.gov NCT04836780. Registered on 8 April 2021 as EARLY-DEX COVID-19.

Efficiency of screening for human immunodeficiency virus infection in emergency departments: a systematic review and meta-analysis. / Eficiencia del cribado de VIH en urgencias: revisión sistemática y metanálisis.

OBJECTIVES: The rates of undiagnosed and late-diagnosed human immunodeficiency virus (HIV) infection are high. Screening for HIV infection in hospital emergency departments (EDs) could offer a way to increase the number of diagnoses. Our aim was to analyze whether universal hospital ED screening for HIV is efficient. MATERIAL AND METHODS: We followed the guidelines for Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). PubMed, the Cochrane Library, LILACS, Scopus, EMBASE, and the Web of Science were searched using the following terms: "HIV infections/epidemiology," "AIDS serodiagnosis," "emergency service, hospital," "prevalence," and "mass screening/methods." The searches were limited to a 5-year time frame (2016-2020); only publications in English or Spanish were collected. We included studies of universal HIV screening among hospital ED patients and evaluated them using the Quality Assessment Tool for Quantitative Studies. RESULTS: A total of 273 articles were identified. Twelve met the inclusion criteria. The studies analyzed 103 731 patient samples and yielded 652 new HIV diagnoses. A random effects model estimated an overall new-diagnosis prevalence of 0.60% (95% CI, 0.39%-0.84%). The heterogeneity statistic I2 was high, at 90.02% (P .001). Estimates of prevalence based on studies carried out in Europe, the United States, and Africa were, respectively, 0.48% (95% CI, 0.13%-1.03%), 0.54% (95% CI, 0.33%-0.40%), and 5.6% (95% CI, 3.37%-9.2%). The studies received quality ratings of moderate or strong. CONCLUSION: Although the reviewed studies applied various screening strategies to identify new HIV diagnoses, our findings support the conclusion that universal screening is efficient.

OBJETIVO: Existe una elevada tasa de infección oculta y diagnóstico tardío en el virus de la inmunodeficiencia hu mana (VIH). La realización de pruebas diagnósticas de infección por VIH en los servicios de urgencias hospitalarios (SUH) puede representar una oportunidad para aumentar el número de diagnósticos. El objetivo de este trabajo es analizar si el cribado universal para el VIH realizado en los SUH es eficiente. METODO: Se realiza una revisión sistemática y metanálisis siguiendo la normativa PRISMA en la base de datos de Pubmed, Cochrane, LILACS, Scopus, EMBASE y WOS utilizando una combinación de términos MESH: "HIV Infections/ epidemiology", "AIDS Serodiagnosis", "Emergency Service, Hospital", "Prevalence", "Mass screening/methods". Los criterios de la búsqueda se centraron en los últimos 5 años (2016-2020) y en los artículos publicados en inglés y en español. Se incluyeron los estudios de pruebas de cribado universal mediante test de cribado de VIH realizadas en los SUH. Para evaluar la calidad de los artículos se utilizó el cuestionario "Quality assessment tool for quantitative studies". RESULTADOS: Se identificaron un total de 273 artículos de los cuales se analizaron finalmente 12 que cumplían los criterios de inclusión. Los estudios incluidos representan un total de 103.731 muestras analizadas obteniéndose un total de 652 nuevos diagnósticos de VIH. La prevalencia conjunta obtenida a través del modelo de efectos aleatorios fue de 0,60% (IC 95%: 0,39-0,84) y el valor del I2 revela una presencia elevada de heterogeneidad (I2 90,02%; p 0,001). La prevalencia conjunta en los estudios incluidos realizados en Europa, América y África fue de 0,48% (IC 95%: 0,13-1,03), 0,54% (IC 95%: 0,33-0,40) y 5,6% (IC 95%: 3,37-9,2), respectivamente. La evaluación de la calidad de los estudios fue de moderada a fuerte. CONCLUSIONES: Aunque las pruebas del VIH pueden realizarse utilizando diferentes estrategias, nuestros datos avalan que una estrategia de cribado universal es eficiente.

Eficiencia del cribado de VIH en urgencias: revisión sistemática y metanálisis / Efficiency of screening for human immunodeficiency virus infection in emergency departments: a systematic review and meta-analysis

Objetivo. Existe una elevada tasa de infección oculta y diagnóstico tardío en el virus de la inmunodeficiencia humana (VIH). La realización de pruebas diagnósticas de infección por VIH en los servicios de urgencias hospitalarios (SUH) puede representar una oportunidad para aumentar el número de diagnósticos. El objetivo de este trabajo es analizar si el cribado universal para el VIH realizado en los SUH es eficiente. Método. Se realiza una revisión sistemática y metanálisis siguiendo la normativa PRISMA en la base de datos de Pubmed, Cochrane, LILACS, Scopus, EMBASE y WOS utilizando una combinación de términos MESH: “HIV Infections/ epidemiology”, “AIDS Serodiagnosis”, “Emergency Service, Hospital”, “Prevalence”, “Mass screening/methods”. Los criterios de la búsqueda se centraron en los últimos 5 años (2016-2020) y en los artículos publicados en inglés y en español. Se incluyeron los estudios de pruebas de cribado universal mediante test de cribado de VIH realizadas en los SUH. Para evaluar la calidad de los artículos se utilizó el cuestionario “Quality assessment tool for quantitative studies”. Resultado. Se identificaron un total de 273 artículos de los cuales se analizaron finalmente 12 que cumplían los criterios de inclusión. Los estudios incluidos representan un total de 103.731 muestras analizadas obteniéndose un total de 652 nuevos diagnósticos de VIH. La prevalencia conjunta obtenida a través del modelo de efectos aleatorios fue de 0,60% (IC 95%: 0,39-0,84) y el valor del I2 revela una presencia elevada de heterogeneidad (I2 90,02%; p < 0,001). La prevalencia conjunta en los estudios incluidos realizados en Europa, América y África fue de 0,48% (IC 95%: 0,13- 1,03), 0,54% (IC 95%: 0,33-0,40) y 5,6% (IC 95%: 3,37-9,2), respectivamente. La evaluación de la calidad de los estudios fue de moderada a fuerte. [...]

Background and objective. The rates of undiagnosed and late-diagnosed human immunodeficiency virus (HIV) infection are high. Screening for HIV infection in hospital emergency departments (EDs) could offer a way to increase the number of diagnoses. Our aim was to analyze whether universal hospital ED screening for HIV is efficient. Methods. We followed the guidelines for Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). PubMed, the Cochrane Library, LILACS, Scopus, EMBASE, and the Web of Science were searched using the following terms: “HIV infections/epidemiology,” “AIDS serodiagnosis,” “emergency service, hospital,” “prevalence,” and “mass screening/methods.” The searches were limited to a 5-year time frame (2016–2020); only publications in English or Spanish were collected. We included studies of universal HIV screening among hospital ED patients and evaluated them using the Quality Assessment Tool for Quantitative Studies. Results. A total of 273 articles were identified. Twelve met the inclusion criteria. The studies analyzed 103731 patient samples and yielded 652 new HIV diagnoses. A random effects model estimated an overall new-diagnosis prevalence of 0.60% (95% CI, 0.39%–0.84%). The heterogeneity statistic I2 was high, at 90.02% (P < .001). Estimates of prevalence based on studies carried out in Europe, the United States, and Africa were, respectively, 0.48% (95% CI, 0.13%–1.03%), 0.54% (95% CI, 0.33%–0.40%), and 5.6% (95% CI, 3.37%–9.2%). The studies received quality ratings of moderate or strong. Conclusion. Although the reviewed studies applied various screening strategies to identify new HIV diagnoses, our findings support the conclusion that universal screening is efficient.

Inadequate use of antibiotics in the covid-19 era: effectiveness of antibiotic therapy.

BACKGROUND: Since December 2019, the COVID-19 pandemic has changed the concept of medicine. This work aims to analyze the use of antibiotics in patients admitted to the hospital due to SARS-CoV-2 infection. METHODS: This work analyzes the use and effectiveness of antibiotics in hospitalized patients with COVID-19 based on data from the SEMI-COVID-19 registry, an initiative to generate knowledge about this disease using data from electronic medical records. Our primary endpoint was all-cause in-hospital mortality according to antibiotic use. The secondary endpoint was the effect of macrolides on mortality. RESULTS: Of 13,932 patients, antibiotics were used in 12,238. The overall death rate was 20.7% and higher among those taking antibiotics (87.8%). Higher mortality was observed with use of all antibiotics (OR 1.40, 95% CI 1.21-1.62; p < .001) except macrolides, which had a higher survival rate (OR 0.70, 95% CI 0.64-0.76; p < .001). The decision to start antibiotics was influenced by presence of increased inflammatory markers and any kind of infiltrate on an x-ray. Patients receiving antibiotics required respiratory support and were transferred to intensive care units more often. CONCLUSIONS: Bacterial co-infection was uncommon among COVID-19 patients, yet use of antibiotics was high. There is insufficient evidence to support widespread use of empiric antibiotics in these patients. Most may not require empiric treatment and if they do, there is promising evidence regarding azithromycin as a potential COVID-19 treatment.

Changes in the profile of newly HIV-diagnosed men who have sex with men, Madrid, 2014 to 2019.

IntroductionKnowing the factors associated with HIV transmission is necessary in order to design preventive programmes tailored to the epidemiological situation in each region and population.AimOur objective was to study the sociodemographic, clinical and behavioural characteristics of men who have sex with men (MSM) who were newly diagnosed with HIV infection.MethodsWe carried out an observational, descriptive, study on all MSM newly diagnosed with HIV infection in one clinic for sexually transmitted infections (STI) and HIV clinic in Madrid between 2014 and 2019. Information on sociodemographic, clinical, and behavioural characteristics of participants per year of diagnosis was collected.ResultsWe detected a total of 1,398 people with HIV infection, 253 of whom were recent seroconverters (rSCV) with a median duration of documented seroconversion of 6 months. From the total, 97.9% infections were sexually transmitted and 2.1% involved injected drugs, i.e. slam practices. The average age was 32.9 years (range: 15.6-74.9), 51.8% were Spanish and 40% Latin American. These diagnoses decreased in Spanish people and increased in Latin Americans during the study period. Of the rSCV, 73.9% had condomless sex under the influence of drugs and 28.9% participated in chemsex sessions. Apps were used by 92.6% rSCV for sexual encounters and 70.4% of them attributed HIV transmission to their use.ConclusionsCombination of HIV prevention strategies, as pre-exposure prophylaxis, should be reinforced among young MSM, especially those born in Latin America, those who use drugs for sex, and those who use apps in search of sexual contacts.

Low use of condom and high STI incidence among men who have sex with men in PrEP programs.

OBJECTIVE: Since the recent introduction of preexposure prophylaxis (PrEP), several studies have reported a decrease in the use of condoms and a rise in STIs among users. This rise in risk behavior associated with the advent of PrEP is known as "risk compensation." The aim of this study is to measure clinical and behavioral changes associated with the introduction of PrEP by analyzing condom use for anal intercourse, number of sexual partners, sexualized drug use and STI incidence. METHODS: We performed a retrospective descriptive study of PrEP users followed every 3months over a 2-year period spanning 2017-2019 in a referral clinic specializing in STI/HIV in Madrid, Spain. One hundred ten men who have sex with men and transgender women underwent regular screening for STIs and hepatitis C virus (HCV) infection. Sociodemographic, clinical, and behavioral data were gathered for all subjects studied. RESULTS: The risk compensation observed in this study consisted primarily of a lower rate of condom use, while the number of sexual partners and recreational drug consumption remained stable. We observed a very high incidence of STIs in this sample, particularly rectal gonorrhea and chlamydia. The factors shown to be independently associated with the presence of an STI on multivariate analysis were age below 30 years and over 10 sexual partners/month. CONCLUSION: The incidence of STI acquisition was higher than expected, indicating a need for strategies to minimize this impact, particularly among younger individuals with a higher number of sexual partners.

Prognostic Impact of Hyponatremia and Hypernatremia in COVID-19 Pneumonia. A HOPE-COVID-19 (Health Outcome Predictive Evaluation for COVID-19) Registry Analysis.

Dysnatremia is associated with increased mortality in patients with community-acquired pneumonia. SARS-COV2 (Severe-acute-respiratory syndrome caused by Coronavirus-type 2) pneumonia can be fatal. The aim of this study was to ascertain whether admittance dysnatremia is associated with mortality, sepsis, or intensive therapy (IT) in patients hospitalized with SARS-COV2 pneumonia. This is a retrospective study of the HOPE-COVID-19 registry, with data collected from January 1th through April 31th, 2020. We selected all hospitalized adult patients with RT-PCR-confirmed SARS-COV2 pneumonia and a registered admission serum sodium level (SNa). Patients were classified as hyponatremic (SNa <135 mmol/L), eunatremic (SNa 135-145 mmol/L), or hypernatremic (SNa >145 mmol/L). Multivariable analyses were performed to elucidate independent relationships of admission hyponatremia and hypernatremia, with mortality, sepsis, or IT during hospitalization. Four thousand six hundred sixty-four patients were analyzed, median age 66 (52-77), 58% males. Death occurred in 988 (21.2%) patients, sepsis was diagnosed in 551 (12%) and IT in 838 (18.4%). Hyponatremia was present in 957/4,664 (20.5%) patients, and hypernatremia in 174/4,664 (3.7%). Both hyponatremia and hypernatremia were associated with mortality and sepsis. Only hyponatremia was associated with IT. In conclusion, hyponatremia and hypernatremia at admission are factors independently associated with mortality and sepsis in patients hospitalized with SARS-COV2 pneumonia. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT04334291, NCT04334291.

Highlights from 22nd International AIDS Conference

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Highlights from 9th Conference on HIV Science from International AIDS Society

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Impact of CD4 and CD8 dynamics and viral rebounds on loss of virological control in HIV controllers.

OBJECTIVE: HIV controllers (HICs) spontaneously maintain HIV viral replication at low level without antiretroviral therapy (ART), a small number of whom will eventually lose this ability to control HIV viremia. The objective was to identify factors associated with loss of virological control. METHODS: HICs were identified in COHERE on the basis of ≥5 consecutive viral loads (VL) ≤500 copies/mL over ≥1 year whilst ART-naive, with the last VL ≤500 copies/mL measured ≥5 years after HIV diagnosis. Loss of virological control was defined as 2 consecutive VL >2000 copies/mL. Duration of HIV control was described using cumulative incidence method, considering loss of virological control, ART initiation and death during virological control as competing outcomes. Factors associated with loss of virological control were identified using Cox models. CD4 and CD8 dynamics were described using mixed-effect linear models. RESULTS: We identified 1067 HICs; 86 lost virological control, 293 initiated ART, and 13 died during virological control. Six years after confirmation of HIC status, the probability of losing virological control, initiating ART and dying were 13%, 37%, and 2%. Current lower CD4/CD8 ratio and a history of transient viral rebounds were associated with an increased risk of losing virological control. CD4 declined and CD8 increased before loss of virological control, and before viral rebounds. DISCUSSION: Expansion of CD8 and decline of CD4 during HIV control may result from repeated low-level viremia. Our findings suggest that in addition to superinfection, other mechanisms, such as low grade viral replication, can lead to loss of virological control in HICs.

Interacciones medicamentosas de etravirina / Etravirine drug interactions

Etravirina (ETR) es un fármaco perteneciente a la familia de los inhibidores de la transcriptasa inversa no análogos de nucleósidos (ITINAN), con actividad antiviral en situaciones de resistencia a los ITINAN de primera generación. Las interacciones farmacológicas producidas por ETR se deben a su efecto dual sobre el sistema CYP450. Es inductor de la actividad de CYP3A4 e inhibidor de la de CYP2C9 y CYP2C19. ETR presenta escasas interacciones farmacológicas clínicamente significativas, entre las que destacan los inhibidores de la proteasa sin potenciar, los ITINAN efavirenz y nevirapina, ritonavir a dosis plena y tipranavir/ritonavir. La interacción con fosamprenavir/ritonavir no es clínicamente significativa, aunque hay una escasa variación de sus valores plasmáticos al administrarse de manera conjunta con ETR. No presenta interacciones con darunavir/ritonavir

Etravirine (ETR) belongs to the family of non-nucleoside analogue reverse transcriptase inhibitors (NNRTIs), with antiviral activity in patients with resistance to first-generation NNRTIs. The drug interactions caused by ETR are due to its dual effect on the CYP450 system. ETR acts as an inducer of CYP3A4 and inhibitor of CYP2C9 and CYP2C19. This drug shows few clinically significant drug interactions, the most important of which involve the unboosted protease inhibitors, the NNRTIs efavirenz and nevirapine, full-dose ritonavir and tipranavir/ritonavir. Interaction with fosamprenavir/ritonavir is not clinically significant, although their plasma levels vary slightly when used in combination with ETR. ETR shows no interactions with darunavir/ritonavir

Tratamiento de la infección por VIH en el paciente con comorbilidad / Treatment of HIV infection in patients with comorbidity

Con frecuencia, los enfermos VIH1 presentan otros procesos concurrentes que condicionan el tratamiento antirretroviral (TARV). Estas modificaciones obedecen a interacciones medicamentosas, a toxicidad específica del tratamiento antirretroviral o a disfunciones del órgano enfermo que alteran el metabolismo de los antirretrovirales. En caso de enfermedad oportunista, la tuberculosis o el linfoma/neoplasia de órgano sólido requieren ciertas consideraciones. Sólo en caso de inmunodepresión grave se iniciará simultáneamente tratamiento antituberculoso y antirretroviral. Si la cifra de CD4 es mayor de 350 cél./ml el TARV se pospondrá hasta finalizar el de la tuberculosis. En caso de linfoma o tumor sólido, una vez conocidos los efectos adversos de la quimioterapia tras los primeros ciclos, se iniciará el TARV. El uso de opiáceos contraindica el inicio del tratamiento por la falta de adhesión, pero puede administrarse si el enfermo toma metadona. La coinfección con el virus de la hepatitis B o C modificará la medicación antirretroviral según el grado de insuficiencia hepatocelular o del tratamiento de estas infecciones. Alguna modificación del TARV consigue mejorar las alteraciones metabólicas o del aspecto del cuerpo. Sin embargo, la hiperlactacidemia requiere la modificación o retirada de los inhibidores de la transcriptasa inversa análogos de nucleósidos (ITIAN). En caso de insuficiencia renal sólo los fármacos que se eliminan por esa vía requieren modificación de la dosis para evitar la toxicidad relacionada con una mayor exposición a los mismos o sus metabolitos. Y ante un cuadro intercurrente grave, la retirada del TARV durante un tiempo limitado no empeora el pronóstico de la infección por VIH (AU)

HIV-positive patients often have concurrent diseases that may condition antiretroviral treatment. Changes may be due to interactions between medicines, specific toxicity of the antiretroviral treatment or malfunction of the diseased organ affecting the metabolism of the antiretrovirals. In cases of opportunist illness, Tuberculosis or Lymphoma/neoplasia of solid organ, certain points must be remembered. Only in case of severe immuno-depression will anti-Tuberculosis and anti-retroviral treatment be initiated simultaneously. If the CD4 figure is over 350, antiretroviral treatment must be postponed till after Tuberculosis. In case of Lymphoma or solid tumour, once the side-effects of chemotherapy after the first cycles are known, antiretroviral treatment will be started. The use of opiates counter-indicates the start of treatment because of lack of adherence, but can be given if the patient is taking methadone. Coinfection with the Hepatitis B or C virus will affect antiretroviral medication, depending on the degree of liver-cell failure and on how the Hepatitis is treated. Some change in the antiretroviral treatment may improve the metabolic disturbances or the appearance of the body. However, Hyperlactacidaemia requires modification or withdrawal of the nucleoside analogues. In case of renal failure only the drugs eliminated through this pathway need their dose adjusted so as to avoid the toxicity related to greater exposure to the drugs or their metabolites. Before a serious intercurrent picture, withdrawal of antiretroviral treatment for a limited period of times does not worsen the prognosis (AU)