Comparative Global Analysis of Stroke Rehabilitation Recommendations Across Income Levels.

BACKGROUND: Successful implementation of stroke rehabilitation guidelines demands high-quality practice standards tailored to targeted sociodemographic contexts. OBJECTIVE: To conduct a scoping review to determine the quality differences in post-stroke rehabilitation practice guidelines (PGs), when comparing high-income countries (HIC) and low or middle-income countries (LMIC). ELIGIBILITY CRITERIA: PGs available in English or Spanish between 2012 and 2021, providing recommendations on post-stroke rehabilitation. SOURCES OF EVIDENCE: Search engines, databases, guideline libraries, gray literature, and references from previous reviews on post-stroke rehabilitation. METHODS: Quality assessment of PGs was performed using 6P's, ELSE, IOM, and AGREE II instruments. We evaluated each item using a scale between 0 to 3, based on the confidence of adherence to the standard. For AGREE II, we followed the instruction manual for scoring. At least two reviewers were independently involved in every step of the process. A cloud-based spreadsheet was used to chart data. We compared the results of PGs originating from HIC with those from MIC. RESULTS: The inclusion criteria were met by 35 documents, which were subjected to evaluation. The study included 21 documents from HIC and 14 from middle-income countries (MIC). No manuscripts from low-income countries were available for inclusion in the study. The quality of PGs from MIC was found to be lower, in terms of methodological rigor and adherence to international recommendations for guidelines development. PGs from both groups of countries failed to include all target audiences and stakeholders (according to the 6P's criteria) and integration of ethical, legal, social, and economic considerations (ELSE). CONCLUSIONS: There are gaps in the quality and availability of stroke rehabilitation guidelines worldwide, especially in LMIC. Designing and providing financial support for the implementation of high-quality guidelines will contribute to more effective implementation strategies in stroke rehabilitation programs and lead to improved patient outcomes.

Diagnostic approach to Aicardi syndrome: A case report.

Aicardi syndrome is an X-linked-dominant genetic condition that is present almost exclusively in females. To diagnose Aicardi syndrome, the classic triad of agenesis of the corpus callosum, infantile spasms, and chorioretinal lacunae must be present. Here, we described a case of a female newborn baby delivered at 36 weeks of gestation that arrived at the emergency department with stiffening of arms and legs; therefore, an electroencephalogram was performed, showing generalized polypots confirming infantile spasms. Moreover, magnetic resonance was performed, showing complete agenesis of the corpus callosum. The patient was then transferred for an ophthalmoscopic examination, which evidenced multiple hypopigmented chorioretinal lesions corresponding to chorioretinal lacunae. Based on the clinical and radiological findings, the diagnosis of Aicardi syndrome was established, and treatment with anticonvulsive therapy and physiotherapy was initiated. This case report highlights the main characteristics that clinicians should consider to suspect this rare genetic condition, emphasizing the imaging and electroencephalographic findings.

Workshop-based learning and networking: a scalable model for research capacity strengthening in low- and middle-income countries.

Science education and research have the potential to drive profound change in low- and middle-income countries (LMICs) through encouraging innovation, attracting industry, and creating job opportunities. However, in LMICs, research capacity is often limited, and acquisition of funding and access to state-of-the-art technologies is challenging. The Alliance for Global Health and Science (the Alliance) was founded as a partnership between the University of California, Berkeley (USA) and Makerere University (Uganda), with the goal of strengthening Makerere University's capacity for bioscience research. The flagship program of the Alliance partnership is the MU/UCB Biosciences Training Program, an in-country, hands-on workshop model that trains a large number of students from Makerere University in infectious disease and molecular biology research. This approach nucleates training of larger and more diverse groups of students, development of mentoring and bi-directional research partnerships, and support of the local economy. Here, we describe the project, its conception, implementation, challenges, and outcomes of bioscience research workshops. We aim to provide a blueprint for workshop implementation, and create a valuable resource for bioscience research capacity strengthening in LMICs.

Frequency and characteristics of HTLV in migrants: results from the +Redivi collaborative network in Spain.

INTRODUCTION: The objective of this study was to describe the main characteristics of migrants diagnosed with human T-lymphotropic virus (HTLV) infection within the +Redivi Spanish network. METHODS: Patients with a diagnosis of HTLV type 1 or 2 in +Redivi from October 2009 to December 2020 were included. Diagnosis was based on positive HTLV serology (enzyme-linked immunosorbent assay (ELISA)/chemiluminescent immunoassay (CLIA)) with line immunoassay (LIA)/Western blot with/without polymerase chain reaction (PCR). RESULTS: A total of 107/17 007 cases (0.6%) had a final diagnosis of HTLV infection: 83 (77.67%) HTLV-1 infections, 6 (5.6%) HTLV-2 infections and 18 (16.8%) non-specified. The majority (76, 71%) were female, median age was 42 years and median time from arrival to Spain until consultation was 10 years. The group included 100 (93.5%) immigrants and 7 (6.6%) visiting friends and relatives (VFR)-immigrants. Most patients were from South America (71, 66.4%), followed by Sub-Saharan Africa (15, 14%) and Central America-Caribbean (13, 12.1%). Around 90% of patients were asymptomatic at presentation and diagnosed as part of screening programs. Median duration of follow-up was 5 years (IQR 2-7). Regarding HTLV-associated conditions, 90 patients (84.2%) had none, 7 (6.5%) had tropical spastic paraparesis , 5 (4.7%) had other associated conditions (dermatitis, uveitis, pulmonary disease), 3 (2.8%) had other neurological symptoms and 2 (1.9%) had adult T-cell leukaemia/lymphoma. No patients with HTLV-2 had HTLV-associated conditions. Four patients (3.7%) died. Concomitant diagnoses were found in 41 (38.3%) patients, including strongyloidiasis in 15 (14%) and HIV co-infection in 4 (3.7%). In 70% of patients, screening of potential contacts was not performed/recorded. CONCLUSIONS: HTLV infections (the majority due to HTLV-1) were mainly diagnosed in asymptomatic migrants from Latin America (generally long-settled immigrants and the majority female with the consequent implications for screening/prevention). A high rate of association with strongyloidiasis was found. In the majority, screening of potential contacts was not performed, representing a missed opportunity for decreasing the under diagnosis of this infection.

A Large Multicenter Prospective Study of Community-Onset Healthcare Associated Bacteremic Urinary Tract Infections in the Era of Multidrug Resistance: Even Worse than Hospital Acquired Infections?

INTRODUCTION: Healthcare-associated (HCA) infections represent a growing public health problem. The aim of this study was to compare community-onset healthcare associated (CO-HCA) bacteremic urinary tract infections (BUTI) and hospital-acquired (HA)-BUTI with special focus on multidrug resistances (MDR) and outcomes. METHODS: ITUBRAS-project is a prospective multicenter cohort study of patients with HCA-BUTI. All consecutive hospitalized adult patients with CO-HCA-BUTI or HA-BUTI episode were included in the study. Exclusion criteria were: patients < 18 years old, non-hospitalized patients, bacteremia from another source or primary bacteremia, non-healthcare-related infections and infections caused by unusual pathogens of the urinary tract. The main outcome variable was 30-day all-cause mortality with day 1 as the first day of positive blood culture. Logistic regression was used to analyze factors associated with clinical cure at hospital discharge and with receiving inappropriate initial antibiotic treatment. Cox regression was used to evaluate 30-day all-cause mortality. RESULTS: Four hundred forty-three episodes were included, 223 CO-HCA-BUTI. Patients with CO-HCA-BUTI were older (p < 0.001) and had more underlying diseases (p = 0.029) than those with HA-BUTI. The severity of the acute illness (Pitt score) was also higher in CO-HCA-BUTI (p = 0.026). Overall, a very high rate of MDR profiles (271/443, 61.2%) was observed, with no statistical differences between groups. In multivariable analysis, inadequate empirical treatment was associated with MDR profile (aOR 3.35; 95% CI 1.77-6.35), Pseudomonas aeruginosa (aOR 2.86; 95% CI 1.27-6.44) and Charlson index (aOR 1.11; 95% CI 1.01-1.23). Mortality was not associated with the site of acquisition of the infection or the presence of MDR profile. However, in the logistic regression analyses patients with CO-HCA-BUTI (aOR 0.61; 95% CI 0.40-0.93) were less likely to present clinical cure. CONCLUSION: The rate of MDR infections was worryingly high in our study. No differences in MDR rates were found between CO-HCA-BUTI and HA-BUTI, in the probability of receiving inappropriate empirical treatment or in 30-day mortality. However, CO-HCA-BUTIs were associated with worse clinical cure.

Evolution, Clinical and Microbiological Characteristics of Invasive Pneumococcal Disease since the Introduction of the Pneumococcal Conjugate Vaccine 13-Valent in Adults over 18 Years Old.

Invasive pneumococcal disease (IPD) presents high mortality in the population at risk. The aim of this work is to know the evolution, clinical and microbiological characteristics of IPD in the adult population of Majorca, since the introduction of a public funded program for pneumococcal conjugate vaccine (PCV-13) in the pediatric population in the Balearic Islands in 2016. For this purpose, a retrospective multicenter study was carried out in which all episodes of IPD in adult patients from the four hospitals of the public health system of Majorca were included, comparing the periods between 2012 and 2015 and between 2016 and 2019. Clinical variables, serotypes and antibiotic sensitivity were collected. There were 498 cases of IPD; 56.8% were male with a mean age of 67 (standard deviation: 16). Most infections were bacterial pneumonias (73.7%). Of the total cases, 264 (53%) presented complications. Of the 498 cases, 351 strains were obtained, of which 145 (41.3%) belong to vaccinal serotypes (included in the PCV-13 vaccine) and 206 (58.7%) to non-vaccinal serotypes (not included in the PCV-13 vaccine). The percentage of IPD caused by vaccinal serotypes was lower in the second period (47.8% vs. 34.5%; p = 0.012).

Validación de criterio de una herramienta de bajo costo para la detección de la pérdida auditiva infantil en Colombia / Criterion validation of a low-cost tool for detecting childhood hearing loss in Colombia / Validação de critério de uma ferramenta de baixo custo para a detecção da perda auditiva infantil na Colômbia

Resumen Objetivo: Establecer la validez de criterio de una herramienta para la detección de la pérdida auditiva en población infantil colombiana. Metodología: Estudio de concordancia en 160 niños entre 5 y 10 años, a quienes se les valoró la audición mediante dos pruebas: la "Herramienta de detección de bajo costo para identificar y clasificar la pérdida auditiva", diseñada en Brasil, y la "Audiometría tonal" como prueba de oro. Se determinó la sensibilidad y la especificidad de la herramienta y la estimación de la concordancia entre las dos pruebas mediante el índice de kappa. Resultados: La "Herramienta de detección de bajo costo para identificar y clasificar la pérdida auditiva" presentó una sensibilidad del 35 %, especificidad del 25 %, un valor predictivo positivo del 12 %, valor predictivo negativo del 56 % y un índice de kappa de -0,24. Conclusión: La "Herramienta de detección de bajo costo para identificar y clasificar la pérdida auditiva" presenta poca capacidad para clasificar correctamente al enfermo como verdadero enfermo y al sano como verdadero sano. Además, la pobre concordancia entre las dos pruebas no permite clasificarla como una herramienta válida para la identificación y la clasificación de la pérdida auditiva en población infantil colombiana. Por lo anterior, se recomienda que cualquier método de tamizaje o de diagnóstico debe cumplir con el proceso de validación antes de ser aplicado en la población. La prevalencia de hipoacusia encontrada fue del 23,1 %.

Abstract Objective: To establish the criteria validity of a tool to detect hearing loss in Colombian children. Methodology: Concordance study in 160 children between 5-10 years old who had their hearing assessed using two tests: the "Low-cost detection tool to identify and classify hearing loss", designed in Brazil, and the "Tonal Audiometry" as the gold standard. The sensitivity and specificity of the tool and the estimation of the agreement between the two tests were determined using the kappa index. Results: The "Low cost detection tool to identify and classify hearing loss" presented a sensitivity of 35%, specificity of 25%, a positive predictive value of 12%, negative predictive value of 56% and a kappa index of -0.24. Conclusion: The "Low-cost detection tool to identify and classify hearing loss" has little capacity to correctly classify the patient as truly ill and the healthy as truly healthy. Furthermore, the poor concordance between the two tests does not allow it to be classified as a valid tool for identifying and classifying hearing loss in Colombian children. It is therefore recommended that any screening or diagnostic method must comply with the validation process before being applied to the population. The prevalence of hearing loss found was 23.1%.

Resumo Objetivo: Estabelecer a validade de critério de uma ferramenta para a detecção da perda auditiva na população infantil colombiana. Metodologia: Estudo de concordância em 160 crianças com idades entre 5 e 10 anos, cuja audição foi avaliada através de dois testes: a "Ferramenta de detecção de baixo custo para identificar e classificar a perda auditiva" desenhada no Brasil, e a "Audiometria tonal" como exame padrão-ouro. Determinou-se a sensibilidade e a especificidade da ferramenta, e a estimativa entre as duas avaliações foi feita através do coeficiente de concordância Kappa. Resultados: A "ferramenta de detecção de baixo custo para identificar e classificar a perda auditiva" apresentou uma sensibilidade de 35%, especificidade de 25%, um valor preditivo positivo de 12%, valor preditivo negativo de 56% e coeficiente de concordância Kappa de -0,24. Conclusão: A "ferramenta de detecção de baixo custo para identificar e classificar a perda auditiva" apresenta pouca capacidade para classificar corretamente o doente como verdadeiro doente e ao sadio como verdadeiro sadio. Além disso, a pobre concordância entre os dois exames não permite classificá-la como uma ferramenta válida para a identificação e a classificação da perda auditiva na população infantil colombiana. Considerando estes resultados, recomenda-se que qualquer método de triagem auditiva ou de diagnóstico, deve cumprir com o proceso de validação antes de ser aplicado na população. A prevalência de perda auditiva encontrada foi de 23,1%.

Prevalence of pulmonary embolism in patients with COVID-19 pneumonia and high D-dimer values: A prospective study.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) pneumonia is associated to systemic hyper-inflammation and abnormal coagulation profile. D-dimer elevation is particularly frequent, and values higher than 1µg/mL have been associated with disease severity and in-hospital mortality. Previous retrospective studies found a high pulmonary embolism (PE) prevalence, however, it should be highlighted that diagnoses were only completed when PE was clinically suspected. MATERIAL AND METHODS: Single-center prospective cohort study. Between April 6th and April 17th 2020, consecutive confirmed cases of COVID-19 pneumonia with D-dimer >1 µg/mL underwent computed tomography pulmonary angiography (CTPA) to investigate the presence and magnitude of PE. Demographic and laboratory data, comorbidities, CTPA scores, administered treatments, and, clinical outcomes were analysed and compared between patients with and without PE. RESULTS: Thirty consecutive patients (11 women) were included. PE was diagnosed in 15 patients (50%). In patients with PE, emboli were located mainly in segmental arteries (86%) and bilaterally (60%). Patients with PE were significantly older (median age 67.0 (IQR 63.0-73.0) vs. 57.0 (IQR 48.0-69.0) years, p = .048) and did not differ in sex or risk factors for thromboembolic disease from the non-PE group. D-dimer, platelet count, and, C reactive protein values were significantly higher among PE patients. D-dimer values correlated with the radiologic magnitude of PE (p<0.001). CONCLUSIONS: Patients with COVID-19 pneumonia and D-dimer values higher than 1 µg/mL presented a high prevalence of PE, regardless of clinical suspicion. We consider that these findings could contribute to improve the prognosis of patients with COVID-19 pneumonia, by initiating anticoagulant therapy when a PE is found.

Heterogeneity in Cystic Echinococcosis Management Among Spanish Centers: Results from a National Survey.

The aim of the study was to evaluate the availability of different procedures, diagnostic tests, and treatments, as well as the procedures and techniques used in the management of cystic echinococcosis (CE) in Spain. This was a cross-sectional study performed from September to December 2018 in Spain. A survey directed to CE-treating clinicians was conducted to collect information regarding the center characteristics and the different protocols of management followed. Thirty-nine centers among 76 contacted centers participated in the survey, most of them belonging to the public health system and attending both adult and children. The median number of patients with CE attended during the last three years per center was 15. Percutaneous techniques were used only in seven centers, and surgery was the most frequently used therapeutic approach. Drugs and duration of treatment (both when administered exclusively or when combined with surgery/puncture, aspiration, injection, and reaspiration) were very variable depending on the centers. There is a high variability in the management of CE among Spanish centers. These results stress the importance of promoting the diffusion of existing knowledge, adapting the WHO recommendations to our setting, and referring patients to referral centers at a national level.

Effectiveness and safety of antiretroviral treatment in pre- and postmenopausal women living with HIV in a multicentre cohort.

BACKGROUND: To compare effectiveness and safety of initial antiretroviral therapy (ART) among premenopausal and postmenopausal women living with HIV aged 45-60 years from the cohort of the Spanish HIV/AIDS Research Network (CoRIS) who initiated ART between 2004 and 2015. METHODS: Multivariable regression models were used to compare post- versus premenopausal women regarding viral suppression (≤50 copies/ml), change in CD4+ T-cell count and time to treatment change (TC) at 48 and 96 weeks after ART initiation. RESULTS: Among 230 women, 154 (67%) were premenopausal at ART initiation. The most frequent initial regimen was tenofovir disoproxil fumarate/emtricitabine/efavirenz prescribed in 49 (32%) premenopausal and 22 (29%) postmenopausal women. The proportion of TC was 35.7% and 30.3% at 48 weeks and 51.3% and 47.4% at 96 weeks, for pre- and postmenopausal women, respectively. There were no significant differences in CD4+ T-cell count changes from ART initiation, viral load suppression, time to TC or reason for TC between both groups. The main reason for TC was occurrence of an adverse event, followed by simplification, in both groups. CONCLUSIONS: ART effectiveness and safety did not differ significantly between pre- and postmenopausal women.

Increased rate of FEV1 decline in HIV patients despite effective treatment with HAART.

INTRODUCTION: Previous studies have reported that the rate of FEV1 decline over time is increased in HIV patients but the mechanisms underlying this observation are unclear. Since current HIV treatment with Highly Active Antiretroviral Therapy (HAART) results in very good immune-viral control, we hypothesized that HAART should normalize the elevated rate of FEV1 decline previously reported in HIV patients if it was somehow related to the immune alterations caused by HIV, particularly in never smokers or quitters, since smoking is a well established risk factor for accelerated FEV1 decline in the general population. METHODS: We explored this hypothesis in a prospectively recruited cohort of 188 HIV (smoker and non-smoker) patients treated with HAART in Palma de Mallorca (Spain) and followed-up for 6 years. The cross-sectional characteristics of this cohort have been published elsewhere. RESULTS: We found that: (1) HAART resulted in good immune-viral control; (2) the rate of FEV1 decline remained abnormally elevated, even in non-smokers and quitters; and, (3) alcohol abuse during follow-up was related to FEV1 decline in these patients. DISCUSSION: Despite adequate immune-viral control by HAART, lung function decline remains increased in most HIV patients, even in non-smokers and quitters. Alcohol abuse is a preventable risk factor to decrease the accelerated FEV1 decline in this population.

Afectación osteoarticular por Streptococcus pneumoniae tras la autorización de las vacunas conjugadas / Osteoarticular infections caused by Streptococcus pneumoniae since authorization of conjugate vaccines

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Drug resistance mutations in HIV-2 patients failing raltegravir and influence on dolutegravir response.

Background: A broader extent of amino acid substitutions in the integrase of HIV-2 compared with HIV-1 might enable greater cross-resistance between raltegravir and dolutegravir in HIV-2 infection. Few studies have examined the virological response to dolutegravir in HIV-2 patients that failed raltegravir. Methods: All patients recorded in the HIV-2 Spanish cohort were examined. The integrase coding region was sequenced in viraemic patients. Changes associated with resistance to raltegravir and dolutegravir in HIV-1 were recorded. Results: From 319 HIV-2-infected patients recorded in the HIV-2 Spanish cohort, 53 integrase sequences from 30 individuals were obtained (20 raltegravir naive and 10 raltegravir experienced). Only one secondary mutation (E138A) was found in one of the 20 raltegravir-naive HIV-2 patients. For raltegravir-experienced individuals, the resistance mutation profile in 9 of 10 viraemic patients was as follows: N155H + A153G/S (four); Y143G + A153S (two); Q148R + G140A/S (two); and Y143C + Q91R (one). Of note, all patients with Y143G and N155H developed a rare non-polymorphic mutation at codon 153. Rescue therapy with dolutegravir was given to 5 of these 10 patients. After >6 months on dolutegravir therapy, three patients with baseline N155H experienced viral rebound. In two of them N155H was replaced by Q148K/R and in another by G118R. Conclusions: A wide repertoire of resistance mutations in the integrase gene occur in HIV-2-infected patients failing on raltegravir. Although dolutegravir may allow successful rescue in most HIV-2 raltegravir failures, we report and characterize three cases of dolutegravir resistance in HIV-2 patients, emerging variants Q148K and Q148R and a novel change G118R.

HIV type 2 epidemic in Spain: challenges and missing opportunities.

: HIV type 2 (HIV-2) is a neglected virus despite estimates of 1-2 million people infected worldwide. HIV-2 is less efficiently transmitted than HIV-1 by sex and from mother to child. Although AIDS may develop in HIV-2 carriers, it takes longer than in HIV-1-infected patients. In contrast with HIV-1 infection, there is no global pandemic caused by HIV-2, as the virus is largely confined to West Africa. In a less extent and due to socioeconomic ties and wars, HIV-2 is prevalent in Portugal and its former colonies in Brazil, India, Mozambique and Angola. Globally, HIV-2 infections are steadily declining over time. A total of 338 cases of HIV-2 infection had been reported at the Spanish HIV-2 registry until December 2016, of whom 63% were men. Overall 72% were sub-Saharan Africans, whereas 16% were native Spaniards. Dual HIV-1 and HIV-2 coinfection was found in 9% of patients. Heterosexual contact was the most likely route of HIV-2 acquisition in more than 90% of cases. Roughly one-third presented with CD4 cell counts less than 200 cells/µl and/or AIDS clinical events. Plasma HIV-2 RNA was undetectable at baseline in 40% of patients. To date, one-third of HIV-2 carriers have received antiretroviral therapy, using integrase inhibitors 32 individuals. New diagnoses of HIV-2 in Spain have remained stable since 2010 with an average of 15 cases yearly. Illegal immigration from Northwestern African borders accounts for over 75% of new HIV-2 diagnoses. Given the relatively large community of West Africans already living in Spain and the continuous flux of immigration from endemic regions, HIV-2 infection either alone or as coinfection with HIV-1 should be excluded once in all HIV-seroreactive persons, especially when showing atypical HIV serological profiles, immunovirological disconnect (CD4 cell count loss despite undetectable HIV-1 viremia) and/or high epidemiological risks (birth in or sex partners from endemic regions).

Pneumococcal infections in elderly patients attending hospital since PCV-13 authorization in Spain.

OBJECTIVES: To study the characteristics and outcomes of pneumococcal infections in patients aged ≥65 years since the authorization of the 13-valent pneumococcal conjugate vaccine (PCV-13) in Spain. METHODS: All pneumococcal pneumonias, empyemas or primary bacteraemias treated at two hospitals in Majorca from 2010 to 2015 were included. Clinical variables, serotypes, and antibiotic susceptibility were collected. RESULTS: Two hundred and forty-nine pneumonias, 11 primary bacteraemias, and 2 empyemas in 243 patients were studied; 181 (69.1%) men, median age 76 years (range: 66-99). Seven (2.6%) were pneumococcal-vaccinated. Bacteraemia was present in 127 (61.9%) cases and related to a higher severity, p= 0.02, and not having chronic lung disease, p = 0.002. Ninety-seven (37%) episodes involved complications and 30 (11.5%) patients died. Mortality was related with the presence of complications at admission, p < 0.001. Only septic shock was more frequent in patients ≥65 years during the period 2010-2015 compared to the period 2006-2010: 38 of 262 (14.5%) vs. 17 of 212 (8%), p = 0.02. Most infections (57.6%) were due to PCV-13 serotypes but were not related to a worse prognosis. The proportion of PCV-13 serotypes tended to decrease from 61% (non-invasive) and 80% (invasive) in 2010-2011 to 33% and 47% in 2014-2015. The antibiotic susceptibility remained stable. CONCLUSIONS: Rates of pneumococcal vaccination in elderly patients with pneumococcal infections were very low. Except for septic shock, the main outcome variables (including mortality) were similar to the ones observed in the period preceding PCV-13 authorization. PCV-13 serotypes were responsible for most infections although they showed a decreasing trend.

Effectiveness of ritonavir-boosted protease inhibitor monotherapy in the clinical setting: same results as in clinical trials? The PIMOCS Study Group.

OBJECTIVES: Ritonavir-boosted protease inhibitor monotherapy (PIMT) is a maintenance strategy that prevents nucleoside reverse transcriptase inhibitor toxicity and reduces costs. Some trials compare PIMT with combined antiretroviral therapy, but restricted selection criteria and low sample size hamper data extrapolation to routine practice. Here, we analyse the effectiveness and safety of PIMT in clinical practice. METHODS: This was a retrospective, observational, multicentre study. Adult HIV-1 patients receiving PIMT with darunavir or lopinavir were included. A Cox regression model identified independent predictors for virological failure (VF). RESULTS: A total of 664 patients (435 on darunavir/ritonavir and 229 on lopinavir/ritonavir) [74% male, median age of 54 years, one-third with previous protease inhibitor VF, CD4 nadir 189 cells/mm(3) and 42% coinfected with hepatitis C virus (HCV)] were analysed. After a median follow-up of 16 months, 78% of patients (95% CI 74%-81%) remained free from therapeutic failure (TF) (change between ritonavir-boosted PIs not considered failure). At 12 months, by intention-to-treat analysis (change between ritonavir-boosted PIs equals failure), 83% of patients were free from TF (87% darunavir/ritonavir versus 77% lopinavir/ritonavir, P = 0.001). Regarding VF, 88% of patients maintained viral suppression at 12 months (93% darunavir/ritonavir versus 88% lopinavir/ritonavir, P = not significant). CD4 nadir <200 cells/mm(3) [hazard ratio (HR) 1.58, 95% CI 1.01-2.49] and undetectable viral load prior to PIMT <24 months (HR 1.86, 95% CI 1.20-2.91) were independent predictors for VF. Prior protease inhibitor failure, HCV coinfection and the protease inhibitor/ritonavir used were not associated with PIMT outcome. A total of 158 patients stopped PIMT, 6% due to adverse events. Two patients developed encephalitis. CONCLUSIONS: PIMT effectiveness was consistent with data from clinical trials. Viral suppression duration prior to PIMT and CD4 cell count nadir were independent predictors for PIMT outcome.

Estudios de transformación genética en arveja voluble cultivar Santa Isabel / Genetic transformation study in climbing pea Santa Isabel cultivar

Se probaron diferentes alternativas de transformación genética en arveja cultivar "Santa Isabel" con el fin de estudiar los factores que afectan el proceso. Se emplearon los métodos de infiltración mediante vacío, infección directa de explantes, transformación de polen, y microinyección de ovarios. La prueba histoquímica de expresión gus fue escogida como método de análisis en la determinación de transformantes positivos. Con las metodologías empleadas se detectaron puntos azules en el tejido vegetal, lo cual indica la expresión transitoria del transgen en los explantes utilizados. Los resultados obtenidos sugieren que la transformación genética en arveja cultivada en Colombia puede ser utilizada para la introducción de genes de interés como apoyo a los procesos de mejoramiento genético.

Different genetic transformation alternatives were tested in pea, "Santa Isabel" cultivar, with the purpose of studying the factors that affect the process. The methods of infiltration with vacuum, direct infection of the explants, pollen transformation and ovary microinjection were used. The hystochemical test of the gus expression was chosen as analysis method in the determination of positive transformants. With the used methodologies, blue spots in the plant tissue were detected, which indicates transient expression of the transgene in utilized explants. The obtained results suggest that the genetic transformation in pea genotypes planted in Colombia can be utilized for the introduction of genes of interest as support to genetic improvement.

Short-term and long-term clinical and immunological consequences of stopping antiretroviral therapy in HIV-infected patients with preserved immune function.

BACKGROUND: The aim of this study was to assess the short-term and long-term consequences of stopping antiretroviral therapy (ART) in patients with preserved immune function. METHODS: This was a randomized 144-week follow-up CD4⁺ T-cell-count-guided treatment-interruption trial. HIV-1-infected adults with plasma HIV-1 RNA<50 copies/ml, CD4⁺ T-cell count >500 cells/µl and nadir CD4⁺ T-cell count >100 cells/µl were randomized to continuous treatment (CT) or treatment interruption (TI) until CD4⁺ T-cell count decreased to <350 cells/µl. The primary end points were AIDS-defining illnesses, death, CD4⁺ T-cell count <200 cells/µl, or virological failure after restarting ART. RESULTS: A total of 106 patients were included, 50 in the CT arm and 56 in the TI arm. A trend to a higher rate of primary end points was observed in the TI group (26.8% versus 14%, difference 12.8%, 95% CI -2.3, 27.8; P=0.105). In addition, 10 patients presented clinical events related with HIV rebound, including 8 cases of thrombocytopaenia. The CD4⁺ T-cell count significantly decreased in the TI group (even in patients with persistently high CD4⁺ T-cell counts and no clinical events) versus the CT group (median change -408 cells/µl versus -21.5 cells/µl; P<0.001), whereas a significant increase in CD8⁺ T-cell count was observed (256 cells/µl versus -59 cells/µl; P<0.001). The time to ART re-initiation was significantly associated with nadir and baseline CD4⁺ T-cell counts. CONCLUSIONS: Discontinuation of ART in patients with preserved immune function is followed by significant immunological impairment even in those with no clinical events, and may be associated with an increased risk of HIV-related complications. Hence, patients who stop ART voluntarily should be closely monitored, regardless of their CD4⁺ T-cell count.

Evolution of HIV-1 genotype in plasma RNA and peripheral blood mononuclear cells proviral DNA after interruption and resumption of antiretroviral therapy.

BACKGROUND: Structured antiretroviral therapy interruption (TI) is discouraged because of poorer AIDS and non-AIDS-related outcomes, but is often inevitable in clinical practice. Certain strategies could reduce the emergence of resistance mutations related to TI. METHODS: A total of 106 HIV-1-infected patients on stable HAART with undetectable plasma viral load were randomized to therapy continuation (n=50) or CD4(+) T-cell-guided TI (n=56). Staggered interruption involved stopping non-nucleoside reverse transcriptase inhibitors (NNRTIs) 7 days before the nucleoside backbone. Genotypic resistance testing (GRT) was performed on proviral DNA from peripheral blood mononuclear cells (PBMCs) at baseline and before each TI, and on plasma RNA after each TI. RESULTS: At baseline, GRT on PBMCs detected mutations in nine patients and only two major mutations were identified. GRT on plasma samples performed after TIs showed nucleoside reverse transcriptase inhibitors (NRTI), NNRTI and protease inhibitor major resistance associated mutations in 10/56, 3/46 and 1/8 patients receiving these drugs, respectively. Only in two patients had the same mutations been observed in GRT on PBMCs at baseline. Three patients presented virological failure after resumption of therapy, all receiving NNRTIs. In one of them, resistance mutations detected at failure had been also observed previously in GRT on plasma after TI. CONCLUSIONS: Staggered interruption of NNRTIs 7 days before the nucleoside backbone does not avoid resistance emergence completely, but does not necessarily lead to virological failure after treatment resumption. Plasma HIV-1 RNA genotype after the interruption and the patient's treatment history seem to be more useful than baseline proviral DNA genotype to assess the risk of virological failure after restarting therapy.