Barriers and facilitators to HIV pre-exposure prophylaxis uptake among transgender women in Colombia: A qualitative analysis using the COM-B model.

Transgender women [TGW] in Colombia are disproportionately affected by HIV due to their low sociodemographic conditions, varied risk behaviours, difficulty accessing health services, and discrimination. Offering pre-exposure prophylaxis [PrEP] as part of a combination of prevention strategies is an appropriate option for this population to reduce their risk of HIV infection. However, little is known about how to implement a PrEP program for TGW in Colombia. Between June and October 2020, we conducted individual interviews with 16 TGW from four different cities in Colombia. The interviews assessed contextual influences, knowledge, skills, perceptions, and beliefs. We used qualitative thematic analysis to identify themes and the Capability, Opportunity, Motivation, and Behavior framework to further delineate barriers and possible interventions. After delineating the main themes across the three subdomains of the model, nine barriers were identified: one related to capability, knowledge, and perception of PrEP; six related to opportunity, which includes, family relations, sexual work environment, stable partner relations, interactions with healthcare workers, health service provision, and community interactions and opportunities; and two related to motivation, mental health, and concerns about medication side effects. Mapping barriers with interventions generated the following intervention functions: education, training, enablement, and environmental structure; and the following policy functions: communication/marketing, legislation, and changes in service provision. Examples of possible interventions are presented and discussed.

Spatial Distribution of Calcium Sparks Determines Their Ability to Induce Afterdepolarizations in Human Atrial Myocytes.

Analysis of the spatio-temporal distribution of calcium sparks showed a preferential increase in sparks near the sarcolemma in atrial myocytes from patients with atrial fibrillation (AF), linked to higher ryanodine receptor (RyR2) phosphorylation at s2808 and lower calsequestrin-2 levels. Mathematical modeling, incorporating modulation of RyR2 gating, showed that only the observed combinations of RyR2 phosphorylation and calsequestrin-2 levels can account for the spatio-temporal distribution of sparks in patients with and without AF. Furthermore, we demonstrate that preferential calcium release near the sarcolemma is key to a higher incidence and amplitude of afterdepolarizations in atrial myocytes from patients with AF.

Increased Density of Endogenous Adenosine A2A Receptors in Atrial Fibrillation: From Cellular and Porcine Models to Human Patients.

Adenosine, an endogenous nucleoside, plays a critical role in maintaining homeostasis during stressful situations, such as energy deprivation or cellular damage. Therefore, extracellular adenosine is generated locally in tissues under conditions such as hypoxia, ischemia, or inflammation. In fact, plasma levels of adenosine in patients with atrial fibrillation (AF) are elevated, which also correlates with an increased density of adenosine A2A receptors (A2ARs) both in the right atrium and in peripheral blood mononuclear cells (PBMCs). The complexity of adenosine-mediated effects in health and disease requires simple and reproducible experimental models of AF. Here, we generate two AF models, namely the cardiomyocyte cell line HL-1 submitted to Anemonia toxin II (ATX-II) and a large animal model of AF, the right atrium tachypaced pig (A-TP). We evaluated the density of endogenous A2AR in those AF models. Treatment of HL-1 cells with ATX-II reduced cell viability, while the density of A2AR increased significantly, as previously observed in cardiomyocytes with AF. Next, we generated the animal model of AF based on tachypacing pigs. In particular, the density of the key calcium regulatory protein calsequestrin-2 was reduced in A-TP animals, which is consistent with the atrial remodelling shown in humans suffering from AF. Likewise, the density of A2AR in the atrium of the AF pig model increased significantly, as also shown in the biopsies of the right atrium of subjects with AF. Overall, our findings revealed that these two experimental models of AF mimicked the alterations in A2AR density observed in patients with AF, making them attractive models for studying the adenosinergic system in AF.

Tratamiento endovascular con técnica de chimenea para patologías del arco aórtico / Endovascular management with chimney technique for pathologies ofthe aortic arch

Introducción. La patología del arco aórtico se ha tratado principalmente con cirugía por vía abierta, pero con una alta morbimortalidad. Las técnicas endovasculares híbridas y las reconstrucciones en "chimenea" son una técnica válida y segura para disminuir el riesgo y la mortalidad. Métodos. Se presentan dos pacientes con patología del arco aórtico y contraindicación de manejo quirúrgico abierto, atendidos en el Servicio de Cirugía Vascular, Hospital Universitario Clínica de San Rafael, Bogotá, D.C., Colombia. Resultados. Se realizaron dos procedimientos endovasculares del arco aórtico para tratar un aneurisma torácico roto y una úlcera aórtica sintomática, con cubrimiento de los troncos supra aórticos con una endoprótesis y canalización de los vasos supra aórticos con prótesis cubiertas y uso de la "técnica de chimenea", de manera exitosa. Discusión. La patología del arco aórtico es de alta complejidad y se asocia con una morbimortalidad elevada por lo que, en los últimos 20 años se han desarrollado diferentes técnicas utilizando procedimientos percutáneos. Conclusión. La "técnica de chimenea" se puede realizar de una manera mínimamente invasiva en pacientes con patología del arco aórtico, no candidatos para cirugía abierta, con resultados exitosos.

Introduction. Aortic arch pathology has been treated mainly by open surgery, but with high morbidity and mortality. Hybrid endovascular techniques and "chimney" reconstructions are a valid and safe techniques to reduce risk and mortality. Method. Two patients with pathology of the aortic arch and contraindication for open surgical management, treated at the Vascular Surgery Service, Hospital Universitario Clínica de San Rafael, Bogotá, Colombia, are presented. Results. Two endovascular aortic procedures were performed successfully to treat a ruptured thoracic aneurysm and a symptomatic aortic ulcer, with coverage of the supra-aortic trunks with an endoprosthesis and cannulation of the supra-aortic vessels with covered prostheses and use of the "chimney technique". Discussion. The pathology of the aortic arch is highly complex and is associated with high morbidity and mortality, being the reason that during the last 20 years, different techniques have been developed using percutaneous procedures. Conclusions. The "chimney technique" can be performed with successful results in a minimally invasive manner in patients with pathology of the aortic arch, who are not candidates for open surgery

AC-2020-12-1420.R1 - HIV care providers' familiarity, concerns, and attitudes about HIV PrEP in Colombia: insights from the PrEP-Col-Study.

In 2019, Colombia approved the combination of tenofovir disoproxil fumarate/emtricitabine for HIV Pre-Exposure Prophylaxis (PrEP). Therefore, we conducted a situational analysis in HIV-care providers to identify barriers and facilitators for PrEP implementation. A survey was applied to a non-probabilistic sample of health care workers of HIV-specialized clinics. We examined PrEP awareness and familiarity, comfort with PrEP-related activities, perceived barriers for PrEP implementation, concerns, and attitudes. Poisson regressions assessed the relationship between these factors and the variable "having a plan to offer PrEP". The participation rate was 41% and included physicians (42.6%) and other health professionals (57.4%). Fifty-one percent of the participants reported more than five years of experience caring for people living with HIV. Forty-two percent of non-physician health care workers were nurses. Most reported high familiarity/comfort with PrEP-relevant activities. Concerns about PrEP were prevalent (> 50%) and included causing more harm than good, reducing condom use, medication non-adherence, drug resistance, and healthcare system barriers. Physicians had a plan to offer PrEP (72.2%) more often than other health professionals (52.6). Having a plan to offer PrEP was related to PrEP knowledge and comfort assessing sexual behavior and providing HIV counseling. Overall, about half of HIV-care providers seemed ready to offer PrEP and constitute an asset for PrEP implementation efforts in Colombia. PrEP awareness among non-physicians, PrEP concerns, and negative attitudes need to be addressed to enhance implementation.

Influence of sex on intracellular calcium homoeostasis in patients with atrial fibrillation.

AIMS: Atrial fibrillation (AF) has been associated with intracellular calcium disturbances in human atrial myocytes, but little is known about the potential influence of sex and we here aimed to address this issue. METHODS AND RESULTS: Alterations in calcium regulatory mechanisms were assessed in human atrial myocytes from patients without AF or with long-standing persistent or permanent AF. Patch-clamp measurements revealed that L-type calcium current (ICa) density was significantly smaller in males with than without AF (-1.15 ± 0.37 vs. -2.06 ± 0.29 pA/pF) but not in females with AF (-1.88 ± 0.40 vs. -2.21 ± 0.0.30 pA/pF). In contrast, transient inward currents (ITi) were more frequent in females with than without AF (1.92 ± 0.36 vs. 1.10 ± 0.19 events/min) but not in males with AF. Moreover, confocal calcium imaging showed that females with AF had more calcium spark sites than those without AF (9.8 ± 1.8 vs. 2.2 ± 1.9 sites/µm2) and sparks were wider (3.0 ± 0.3 vs. 2.2 ± 0.3 µm) and lasted longer (79 ± 6 vs. 55 ± 8 ms), favouring their fusion into calcium waves that triggers ITIs and afterdepolarizations. This was linked to higher ryanodine receptor phosphorylation at s2808 in women with AF, and inhibition of adenosine A2A or beta-adrenergic receptors that modulate s2808 phosphorylation was able to reduce the higher incidence of ITI in women with AF. CONCLUSION: Perturbations of the calcium homoeostasis in AF is sex-dependent, concurring with increased spontaneous SR calcium release-induced electrical activity in women but not in men, and with diminished ICa density in men only.

Scales to Assess Knowledge, Motivation, and Self-Efficacy for HIV PrEP in Colombian MSM: PrEP-COL Study.

OBJECTIVE: We evaluated the construct validity Spanish version of knowledge, stigma, norms, and self-efficacy scales regarding PrEP in MSM. METHODS: Sample of 287 MSM. Exploratory confirmatory factor analysis and item response theory were used to validate the constructs. Correlations and confidence interval-based estimation of relevance analyses were conducted to correlate the scales with willingness and intention to use PrEP. RESULTS: Attitude, stigma, and descriptive and subjective norms scales showed good construct validity and were related to intention and willingness to use PrEP. However, the knowledge scale and self-efficacy scales require further refinement. CONCLUSIONS: The study provides useful information for assessing information, motivation, and self-efficacy related to PrEP use. Our results could be used to test the scales and the theoretical model in other contexts to confirm their usefulness.

Massive Gene Loss and Function Shuffling in Appendicularians Stretch the Boundaries of Chordate Wnt Family Evolution.

Gene loss is a pervasive source of genetic variation that influences species evolvability, biodiversity and the innovation of evolutionary adaptations. To better understand the evolutionary patterns and impact of gene loss, here we investigate as a case study the evolution of the wingless (Wnt) family in the appendicularian tunicate Oikopleura dioica, an emergent EvoDevo model characterized by its proneness to lose genes among chordates. Genome survey and phylogenetic analyses reveal that only four of the thirteen Wnt subfamilies have survived in O. dioica-Wnt5, Wnt10, Wnt11, and Wnt16,-representing the minimal Wnt repertoire described in chordates. While the loss of Wnt4 and Wnt8 likely occurred in the last common ancestor of tunicates, representing therefore a synapomorphy of this subphylum, the rest of losses occurred during the evolution of appendicularians. This work provides the first complete Wnt developmental expression atlas in a tunicate and the first insights into the evolution of Wnt developmental functions in appendicularians. Our work highlights three main evolutionary patterns of gene loss: (1) conservation of ancestral Wnt expression domains not affected by gene losses; (2) function shuffling among Wnt paralogs accompanied by gene losses; and (3) extinction of Wnt expression in certain embryonic directly correlated with gene losses. Overall our work reveals that in contrast to "conservative" pattern of evolution of cephalochordates and vertebrates, O. dioica shows an even more radical "liberal" evolutionary pattern than that described ascidian tunicates, stretching the boundaries of the malleability of Wnt family evolution in chordates.

New approach for the dimensionless analysis of a unidirectional flow solar reactor based on Damköhler's number profiles.

A methodology for the analysis of the behavior of complex reactors based on the construction of profiles of a dimensionless number (Damköhler) for each main chemical species ( D a i ) was proposed. A 4-chlorophenol mineralization reaction in a heterogeneous solar reactor with suspended TiO2 and addition of H2O2 with tubular geometry and radiation collectors, fluid flow and a recirculation system was selected as a complex model system in order to validate the approach. The dynamic behavior of the reactor in dimensionless variables was modeled as a function of D a i . Where D a i ( z , t ) is a local property and grouped the optical and surface's properties of the catalyst, catalyst load, radiation intensity, the photon absorption rate, rate of non-photochemical reactions, the H2O2 effect, the reaction rate of different stages like adsorption, attack of radicals, surface reactions, plus design and operation variables like reactor volume and volumetric flow. A coupling of orthogonal collocation and Runge-Kutta methods were used to solve the PDEs and carry out the simulations to the different experimental conditions, resulting in profiles of D a i , C i , and conversion in function of time and space. The D a i profiles proposed in the new methodology are capable of describing the disturbances in solar reactors, to indicate consumption and generation rates, instantaneous changes of reaction rate, to describe competitive reactions and quenching effects and to determine equilibrium concentrations, all of the above at each time and space. Therefore, this approach is a analysis tool of reactors which complements the concentration profile. This methodology can be extended to other reactive systems, adapting the intrinsic reaction rates.

Adenosine A2A Receptors Are Upregulated in Peripheral Blood Mononuclear Cells from Atrial Fibrillation Patients.

Atrial fibrillation (AF) is the most common form of cardiac arrhythmia seen in clinical practice. While some clinical parameters may predict the transition from paroxysmal to persistent AF, the molecular mechanisms behind the AF perpetuation are poorly understood. Thus, oxidative stress, calcium overload and inflammation, among others, are believed to be involved in AF-induced atrial remodelling. Interestingly, adenosine and its receptors have also been related to AF development and perpetuation. Here, we investigated the expression of adenosine A2A receptor (A2AR) both in right atrium biopsies and peripheral blood mononuclear cells (PBMCs) from non-dilated sinus rhythm (ndSR), dilated sinus rhythm (dSR) and AF patients. In addition, plasma adenosine content and adenosine deaminase (ADA) activity in these subjects were also determined. Our results revealed increased A2AR expression in the right atrium from AF patients, as previously described. Interestingly, increased levels of adenosine content and reduced ADA activity in plasma from AF patients were detected. An increase was observed when A2AR expression was assessed in PBMCs from AF subjects. Importantly, a positive correlation (P=0.001) between A2AR expression in the right atrium and PBMCs was observed. Overall, these results highlight the importance of the A2AR in AF and suggest that the evaluation of this receptor in PBMCs may be potentially be useful in monitoring disease severity and the efficacy of pharmacological treatments in AF patients.

Inhibition of Tryptophan Hydroxylases and Monoamine Oxidase-A by the Proton Pump Inhibitor, Omeprazole-In Vitro and In Vivo Investigations.

Serotonin (5-HT) is a hormone and neurotransmitter that modulates neural activity as well as a wide range of other physiological processes including cardiovascular function, bowel motility, and platelet aggregation. 5-HT synthesis is catalyzed by tryptophan hydroxylase (TPH) which exists as two distinct isoforms; TPH1 and TPH2, which are responsible for peripheral and central 5-HT, respectively. Due to the implication of 5-HT in a number of pathologies, including depression, anxiety, autism, sexual dysfunction, irritable bowel syndrome, inflammatory bowel disease, and carcinoid syndrome, there has been a growing interest in finding modulators of these enzymes in recent years. We thus performed high-throughput screening (HTS) using a fluorescence-based thermal shift assay (DSF) to search the Prestwick Chemical Library containing 1,280 compounds, mostly FDA-approved drugs, for TPH1 binders. We here report the identification of omeprazole, a proton pump inhibitor, as an inhibitor of TPH1 and TPH2 with low micromolar potency and high selectivity over the other aromatic amino acid hydroxylases. The S-enantiomer of omeprazole, esomeprazole, has recently also been described as an inhibitor of monoamine oxidase-A (MAO-A), the main enzyme responsible for 5-HT degradation, albeit with lower potency compared to the effect on TPH1 and TPH2. In order to investigate the net effect of simultaneous inhibition of TPH and MAO-A in vivo, we administered high-dose (100 mg/kg) omeprazole to CD-1 mice for 4 days, after which the animals were subjected to the tail suspension test. Finally, central (whole brain) and peripheral (serum) 5-HT content was measured using liquid chromatography-mass spectrometry (LC-MS). Omeprazole treatment significantly increased 5-HT concentrations, both in brain and in serum, and reduced the time spent immobile in the tail suspension test relative to vehicle control. Thus, the MAO-A inhibition afforded by high-dose omeprazole appears to overcome the opposing effect on 5-HT produced by inhibition of TPH1 and TPH2. Further modification of proton pump inhibitor scaffolds may yield more selective modulators of 5-HT metabolism.

Sizing of reactors by charts of Damköhler's number for solutions of dimensionless design equations.

The reaction kinetic rate and mass transport play an important role in the sizing and scale-up of reactors. The Damköhler's dimensionless number ( D a ) is the quotient of these effects. A new interpretation of D a as a local property is introduced D a ( x , y , z , t ) . A new graphical methodology is proposed for the sizing and scale-up of unidirectional flow reactors and CSTRs. The partial differential equation (PDE) and algebraic that describe the continuity within these reactors transform into dimensionless variables, and the conversion at the output is expressed as a function of the conditions at the input D a 0 . The operating conditions as volumetric flow, residence time; design variables as reactor volume; and intrinsic reaction rate are involved in D a 0 . The equations are solved numerically to develop the design charts D a 0 vs X. The design volume is linear with D a 0 , and the conversion is obtained from the charts ( D a 0 vs X) or vice versa. Using these charts avoids the analytical or numerical solution of the PDE that governs the unidirectional flow reactors becoming an easy tool for scale-up. The article portrays how to use these diagrams. Reactors with D a 0 < 0.1 have a low conversion per pass, the charts also allow estimating the number of recirculations required as a function of the overall conversion. Reactors with the same conversion have the same D a 0 , both laboratory and industrial scale. Then, the D a number is presented as a fundamental parameter for design and scaling-up these reactors.

Examining a syndemic framework for HIV and sexually transmitted infections risk in Cali, Colombia / Examinando un marco sindémico para el VIH y el riesgo de infecciones de transmisión sexual en Cali, Colombia / Examinando um marco sindémico para o vih e o risco de infeções de transmissão sexual em Cali, Colômbia

Abstract Objective: We examined the role played by four psychosocial conditions: forced sex, early sexual initiation, and misuse of alcohol and illicit drugs on the risk of HIV and sexually transmitted infections in Cali-Colombia between 2013 and 2015. Methods: Using data from an HIV counseling and testing campaign in Cali, Colombia, we tested the effect of the accumulation and interactions of the four psychosocial conditions on both outcomes. Results: A total of 604 participants were representative subjects from key affected communities: men who have sex with men, transgender women and female sex workers. A total of 733 participants were heterosexual women and men. Only drug abuse was associated with HIV positivity (Prevalence ratio=2.3, CI 95%: 1.3-4.1), while all psychosocial conditions were associated with sexually transmitted infection history. The accumulation of the syndemic conditions was related to a higher likelihood of sexually transmitted infection history. None of the interactions tested was significant. Conclusions: Our findings highlight the importance of comprehensive mental health interventions in addressing HIV epidemics in Colombia.

Resumen Objetivo: Examinar el papel desempeñado por cuatro afecciones psicosociales: sexo forzado, iniciación sexual temprana, uso inadecuado de alcohol y drogas ilícitas en el riesgo de VIH e infecciones de transmisión sexual, en Cali-Colombia entre 2013-2015. Métodos: Utilizando datos de una campaña de consejería y pruebas de VIH en Cali, Colombia, probamos el efecto de la acumulación e interacciones de las cuatro condiciones psicosociales en la positividad al VIH y la positividad a otras enfermedades de transmisión sexual. Resultados: 604 participantes de las principales comunidades afectadas: hombres que tienen sexo con hombres, mujeres transgénero y trabajadoras sexuales. 733 participantes mujeres y hombres heterosexuales. Solo, abuso de drogas se asoció con positividad VIH (Razón de prevalencia = 2.3, IC 95%: 1.3-4.1), mientras que, todas las condiciones psicosociales se asociaron con historia de infecciones de transmisión sexual. La acumulación de condiciones sindémicas se relacionó con mayor probabilidad de historia de infecciones de transmisión sexual. Ninguna interacción probada fue significativa. Conclusiones: Nuestros hallazgos resaltan la importancia de intervenciones integrales de salud mental para abordar la epidemia de VIH en Colombia.

Resumo Objetivo: Examinar o papel desempenhado por quatro afeções psicossociais: sexo forçado, iniciação sexual precoce, uso inadequado de álcool e drogas ilícitas no risco de VIH e infeções de transmissão sexual, em Cali-Colômbia entre 2013-2015. Métodos: Utilizando dados duma campanha de aconselhamento e testes de VIH em Cali, Colômbia, testamos o efeito da acumulação e interações das quatro condições psicossociais na positividade ao VIH e a positividade a outras doenças de transmissão sexual. Resultados: 604 participantes das principais comunidades afetadas: homens que tem sexo com homens, mulheres transgênero e trabalhadoras sexuais. 733 participantes mulheres e homens heterossexuais. Só, abuso de drogas se associou com positividade VIH (Razão de prevalência = 2.3, IC 95%: 1.3-4.1), enquanto que, todas as condições psicossociais se associaram com história de infeções de transmissão sexual. Acumulação de condições sindémicas (palavra que reúne o social e o biológico) se relacionou com maior probabilidade de história de infeções de transmissão sexual. Nenhuma interação provada foi significativa. Conclusões: Nossos descobrimentos ressaltam a importância de intervenções integrais de saúde mental para abordar a epidemia de VIH na Colômbia.

Examining a syndemic framework for HIV and Sexually Transmitted Infections Risk in Cali, Colombia / Examinando un marco sindémico para el VIH y el riesgo de infecciones de transmisión sexual en Cali, Colombia / Examinando um marco sindémico para o vih e o risco de infeções de transmissão sexual em Cali, Colômbia

Objective: We examined the role played by four psychosocial conditions: forced sex, early sexual initiation, and misuse of alcohol and illicit drugs on the risk of HIV and sexually transmitted infections in Cali-Colombia between 2013 and 2015. Methods: Using data from an HIV counseling and testing campaign in Cali, Colombia, we tested the effect of the accumulation and interactions of the four psychosocial conditions on both outcomes. Results: A total of 604 participants were representative subjects from key affected communities: men who have sex with men, transgender women and female sex workers. A total of 733 participants were heterosexual women and men. Only drug abuse was associated with HIV positivity (Prevalence ratio=2.3, CI 95%: 1.3­4.1), while all psychosocial conditions were associated with sexually transmitted infection history. The accumulation of the syndemic conditions was related to a higher likelihood of sexually transmitted infection history. None of the interactions tested was significant. Conclusions: Our findings highlight the importance of comprehensive mental health interventions in addressing HIV epidemics in Colombia.

Objetivo: Examinar el papel desempeñado por cuatro afecciones psicosociales: sexo forzado, iniciación sexual temprana, uso inadecuado de alcohol y drogas ilícitas en el riesgo de VIH e infecciones de transmisión sexual, en Cali-Colombia entre 2013-2015. Métodos: Utilizando datos de una campaña de consejería y pruebas de VIH en Cali, Colombia, probamos el efecto de la acumulación e interacciones de las cuatro condiciones psicosociales en la positividad al VIH y la positividad a otras enfermedades de transmisión sexual. Resultados: 604 participantes de las principales comunidades afectadas: hombres que tienen sexo con hombres, mujeres transgénero y trabajadoras sexuales. 733 participantes mujeres y hombres heterosexuales. Solo, abuso de drogas se asoció con positividad VIH (Razón de prevalencia = 2.3, IC 95%: 1.3­4.1), mientras que, todas las condiciones psicosociales se asociaron con historia de infecciones de transmisión sexual. La acumulación de condiciones sindémicas se relacionó con mayor probabilidad de historia de infecciones de transmisión sexual. Ninguna interacción probada fue significativa. Conclusiones: Nuestros hallazgos resaltan la importancia de intervenciones integrales de salud mental para abordar la epidemia de VIH en Colombia

Objetivo: Examinar o papel desempenhado por quatro afeções psicossociais: sexo forçado, iniciação sexual precoce, uso inadequado de álcool e drogas ilícitas no risco de VIH e infeções de transmissão sexual, em Cali-Colômbia entre 2013-2015. Métodos: Utilizando dados duma campanha de aconselhamento e testes de VIH em Cali, Colômbia, testamos o efeito da acumulação e interações das quatro condições psicossociais na positividade ao VIH e a positividade a outras doenças de transmissão sexual. Resultados: 604 participantes das principais comunidades afetadas: homens que tem sexo com homens, mulheres transgênero e trabalhadoras sexuais. 733 participantes mulheres e homens heterossexuais. Só, abuso de drogas se associou com positividade VIH (Razão de prevalência = 2.3, IC 95%: 1.3­4.1), enquanto que, todas as condições psicossociais se associaram com história de infeções de transmissão sexual. Acumulação de condições sindémicas (palavra que reúne o social e o biológico) se relacionou com maior probabilidade de história de infeções de transmissão sexual. Nenhuma interação provada foi significativa. Conclusões: Nossos descobrimentos ressaltam a importância de intervenções integrais de saúde mental para abordar a epidemia de VIH na Colômbia.

Resistance to antiretroviral therapy (ART) in patients with HIV/AIDS after therapeutic failure / Resistencia a la terapia antirretroviral (TAR) en pacientes VIH/SIDA en fracaso terapéutico

Abstract Introduction: HIV replication and the suboptimal use of antiretrovirals are directly related to the appearance of resistant mutations. The objective of this study was to describe the resistance mutations (RMs) present in HIV infected patients who experienced antiretroviral treatment failure between 2002 and 2015 in Cali, Colombia. Method: 403 genotypes of adult patients with HIV/AIDS who received ART and experienced virological failure were analyzed. With informed consent, resistance genotype testing was performed using TRUGENE HIV-1; the RMs were defined according to the International AIDS Society-2015 list. The sample was subdivided by periods (2002-2006 vs 2007-2015) and early versus late genotyping. Mutations with ≥15 points to some ARV were considered, according to the Stanford HIV database. Results: comparing the periods, there were more RMs for non-nucleoside reverse transcriptase inhibitors (NNRTIs) in 2007-2015 than in 2002-2006 (85% vs. 60%, respectively, p<0.0001), but protease inhibitors were less affected in 2007-2015 than in 2002-2006 (11% vs. 29%, respectively, p < 0.001). The M184V and K103 N mutations were the most frequent RMs in reverse transcriptase (RT) for NRTIs and NNRTIs, respectively. A total of 67.5% were early genotypes. There was a higher prevalence of certain RMs in late genotypes compared to early ones, mainly for RMs to PIs (D30N, L90M) and NRTIs (M41L, D67N, K70R, L210W); but a lower prevalence of RMs to NNRTIs (Y181C). Conclusion: the late resistance genotypes were associated with higher levels of resistance mutations, mainly to the NNRTI and NRTI families, limiting their use as a rescue therapy alternative. (Acta Med Colomb 2019; 44. DOI:https://doi.org/10.36104/amc.2019.1546).

Resumen Introducción: la replicación del VIH y la utilización subóptima de antirretrovirales, se relacionan directamente con la aparición de mutaciones de resistencias. el objetivo del estudio fue describir las mutaciones de resistencia (mdr) presentes en pacientes infectados por vih que fracasaron a la terapia antirretroviral entre 2002 y 2015 en cali, colombia. Metodología: se analizaron 403 genotipos de pacientes adultos con VIH/SIDA que recibían TAR y experimentaban fracaso virológico. Bajo consentimiento informado, se llevó a cabo la prueba de genotipo de resistências usando TRUGENE HIV-1, se definieron las MDR según el listado de International AIDS Society-2015. Se subdividió la muestra por periodos (2002-2006 vs 2007-2015) y momento de genotipificación temprano versus tardio. Mutaciones con ≥15 puntos a algún ARV fueron consideradas, según la HIV-database de Stanford. Resultados: comparando los periodos, en 2007-2015 hubo mayor afectación de MDR para los inhibidores no nucleosídicos de la transcriptasa reversa (ITINAN) frente a 2002-2006 (85% vs. 60%, respectivamente, p<0.0001), pero menor afectación en 2007-2015 frente a 2002-2006 para inhibidores de la proteasa (11% vs. 29%, respectivamente p < 0.001). Mutaciones M184V y K103N fueron las MDR más frecuentes en la retrotranscriptasa (RT) para ITIAN e ITINAN, respectivamente. El 67.5% fueron genotipos considerados tempranos. Mayor prevalencia de ciertas MDR cuando el genotipo fue tardío frente al temprano, principalmente para MDR a IP (D30N, L90M), ITIAN (M41L, D67N, K70R, L210W), pero menor para MDR a ITINAN (Y181C). Conclusion: los estudios de genotipo de resistencias realizados tardiamente, se asociaron con mayores niveles de mutaciones que confieren resistencias, principalmente a las familias de ITINAN e ITIAN, limitando su uso como alternativa terapéutica de rescate. (Acta Med Colomb 2019; 44. DOI:https://doi.org/10.36104/amc.2019.1546).

[Effectiveness and safety of generic version of lamivudine/tenofovir and efavirenz in treatment naïve HIV-infected patients: a nonrandomized, open-label, phase IV study in Cali-Colombia, 2012-2014]. / Efectividad y seguridad del esquema genérico lamivudina/tenofovir y efavirenz en pacientes con VIH/SIDA naïve: estudio fase IV no aleatorizado, Cali-Colombia 2012-2014.

BACKGROUND: Clinical studies aimed to evaluating the quality of generic drugs may be useful to strengthen policies of access to combined antiretroviral therapy (cART). AIM: To describe the effectiveness and safety of the generic schema lamivudine/tenofovir/efavirenz (3TC/TDF/EFV) in patients with HIV/AIDS naive, belonging to a comprehensive care program. METHODS: A nonrandomized, open-label, phase IV study, during 2012 to 2014 naive HIV-infected patients 18 years or older with indication to receive cART were recruited. Patients were treated with generic scheme 3TC/TDF/EFV and were followed-up during 12 months. Clinical, immunological and laboratory parameters were assessed at baseline, 3, 6 and 12 months of treatment. RESULTS: Of the 40 patients, 30 (75%) met the 12 months of treatment; of them, 80% achieved undetectable viral load (< 40 copies/mL) and 83.3% viral load < 50 copies/mL. Additionally, there was a significant increase (173 cells/mm3) in the median for CD4 T lymphocyte count. Moreover, the results of the whole blood count, creatinine and transaminases were preserved in normal ranges and did not generate changes in the cART. Potential side effects of antiretroviral drugs occurred in less than 10% of patients and had no serious implications. CONCLUSIONS: In this small group of patients, the generic scheme 3TC/TDF/EFV is effective and safe in the treatment of patients with HIV/AIDS naïve, and its effectiveness and safety profile is similar to show by innovator scheme 3TC/TDF/EFV in patients with similar clinical conditions. Registro Estudio: Registro Público Cubano de Ensayos Clínicos (RPCEC) ID: RPCEC00000134. Registered 20 July 2012.

Psychometric properties and validity of the Center for Epidemiological Studies Depression Scale (CES-D) in a population attending an HIV clinic in Cali, Colombia / Propiedades psicométricas y validez de la escala de depresión del Center for Epidemiological Studies (CES-D) en personas atendidas en una clínica de HIV en Cali, Colombia

INTRODUCTION: Depression in people living with HIV/AIDS is associated with poor health outcomes. Despite this, assessment of depressive symptoms is not a routine clinical practice in the care of people with HIV in Colombia. One reason could be the lack of validated depression screening scales for this population. OBJECTIVE: To test the reliability and construct validity of the 20- and 10-item-Center for Epidemiological Studies Depression Scale in patients attending an HIV clinic in Cali, Colombia. MATERIALS AND METHODS: A non-random sample of 105 adults was enrolled. The 20 item-CES-D (CES-D-20) scale was administered twice: At baseline and 2-4 weeks later. We calculated the Cronbach's alpha coefficient and the intraclass correlation coefficient. In addition, we used an exploratory and confirmatory factorial analysis, as well as the item response theory to assess the validity of the scale. RESULTS: Most participants were men (73%), with a mean age of 40 years, 53% of whom had not completed high school. Cronbach's coefficients were 0.92 and 0.94 at baseline and at the second interview, respectively. The intraclass correlation was 0.81 (95% CI: 0.72-0.88). Although all 20 items loaded distinctly in 4 factors, 5 items did not load as expected. The structure factor of the CES-D-20 was not confirmed, as 4 items had poor goodness of fit. The CES-D-10 appeared to perform better in this population. CONCLUSIONS: These results support the reliability and validity of the CES-D-10 instrument to screen for depressive symptoms in people living with HIV in Colombia.

Introducción. La depresión en personas con HIV/sida se asocia con resultados negativos para la salud. La evaluación de los síntomas depresivos no es una práctica clínica rutinaria en el cuidado de personas con HIV/sida en Colombia, lo cual puede deberse a la carencia de escalas validadas para la tamización de la depresión en esta población. Objetivo. Evaluar la reproducibilidad y validez de constructo de dos versiones de la escala de depresión del Center for Epidemiological Studies (CES-D), la de 20 ítems y la de 10 ítems, en personas con HIV/sida atendidas en una clínica de Cali, Colombia. Materiales y métodos. Se seleccionó una muestra no probabilística de 105 adultos con HIV/sida. La escala CES-D se utilizó dos veces (línea basal y 2 a 4 semanas después). La consistencia interna fue evaluada con el coeficiente alfa de Cronbach. La reproducibilidad se evaluó con el coeficiente de correlación intraclase. Para verificar la validez del constructo se utilizó un análisis factorial exploratorio y la teoría de respuesta al ítem. Resultados. El 73 % de la muestra correspondía a hombres, la edad promedio fue de 40 años y el 53 % tenía baja escolaridad. El coeficiente alfa de Cronbach fue de 0,92 (línea basal) y de 0,94 (segunda entrevista). El coeficiente de correlación intraclase fue de 0,81 (IC95% 0,72-0,88). Aunque en cuatro de los factores en la escala de 20 ítems claramente hubo carga factorial, cinco de los ítems no tuvieron un ajuste adecuado. La CES-D de 10 ítems parece funcionar mejor en esta población. Conclusiones. Los resultados respaldaron la reproducibilidad y la validez de la escala CES-D para la tamización de síntomas depresivos en personas con HIV/sida en Colombia.

Psychometric properties and validity of the Center for Epidemiological Studies Depression Scale (CES-D) in a population attending an HIV clinic in Cali,Colombia / Propiedades psicométricas y validez de la escala de depresión del Center for Epidemiological Studies (CES-D) en personas atendidas en una clínica de HIV en Cali, Colombia

Abstract Introduction: Depression in people living with HIV/AIDS is associated with poor health outcomes. Despite this, assessment of depressive symptoms is not a routine clinical practice in the care of people with HIV in Colombia. One reason could be the lack of validated depression screening scales for this population. Objective: To test the reliability and construct validity of the 20- and 10-item-Center for Epidemiological Studies Depression Scale in patients attending an HIV clinic in Cali, Colombia. Materials and methods: A non-random sample of 105 adults was enrolled. The 20 item- CES-D (CES-D-20) scale was administered twice: At baseline and 2-4 weeks later. We calculated the Cronbach's alpha coefficient and the intraclass correlation coefficient. In addition, we used an exploratory and confirmatory factorial analysis, as well as the item response theory to assess the validity of the scale. Results: Most participants were men (73%), with a mean age of 40 years, 53% of whom had not completed high school. Cronbach's coefficients were 0.92 and 0.94 at baseline and at the second interview, respectively. The intraclass correlation was 0.81 (95% CI: 0.72- 0.88). Although all 20 items loaded distinctly in 4 factors, 5 items did not load as expected. The structure factor of the CES-D-20 was not confirmed, as 4 items had poor goodness of fit. The CES-D-10 appeared to perform better in this population. Conclusions: These results support the reliability and validity of the CES-D-10 instrument to screen for depressive symptoms in people living with HIV in Colombia.

Resumen Introducción: La depresión en personas con HIV/sida se asocia con resultados negativos para la salud. La evaluación de los síntomas depresivos no es una práctica clínica rutinaria en el cuidado de personas con HIV/sida en Colombia, lo cual puede deberse a la carencia de escalas validadas para la tamización de la depresión en esta población. Objetivo. Evaluar la reproducibilidad y validez de constructo de dos versiones de la escala de depresión del Center for Epidemiological Studies (CES-D), la de 20 ítems y la de 10 ítems, en personas con HIV/sida atendidas en una clínica de Cali, Colombia. Materiales y métodos. Se seleccionó una muestra no probabilística de 105 adultos con HIV/sida. La escala CES-D se utilizó dos veces (línea basal y 2 a 4 semanas después). La consistencia interna fue evaluada con el coeficiente alfa de Cronbach. La reproducibilidad se evaluó con el coeficiente de correlación intraclase. Para verificar la validez del constructo se utilizó un análisis factorial exploratorio y la teoría de respuesta al ítem. Resultados. El 73 % de la muestra correspondía a hombres, la edad promedio fue de 40 años y el 53 % tenía baja escolaridad. El coeficiente alfa de Cronbach fue de 0,92 (línea basal) y de 0,94 (segunda entrevista). El coeficiente de correlación intraclase fue de 0,81 (IC95% 0,72-0,88). Aunque en cuatro de los factores en la escala de 20 ítems claramente hubo carga factorial, cinco de los ítems no tuvieron un ajuste adecuado. La CES-D de 10 ítems parece funcionar mejor en esta población. Conclusiones. Los resultados respaldaron la reproducibilidad y la validez de la escala CES-D para la tamización de síntomas depresivos en personas con HIV/sida en Colombia.

Efectividad y seguridad del esquema genérico lamivudina/tenofovir y efavirenz en pacientes con VIH/SIDA naïve: estudio fase IV no aleatorizado, Cali-Colombia 2012-2014 / Effectiveness and safety of generic version of lamivudine/tenofovir and efavirenz in treatment naïve HIV-infected patients: a nonrandomized, open-label, phase IV study in Cali-Colombia, 2012-2014

Resumen Antecedentes: Los estudios clínicos orientados a evaluar la calidad de medicamentos genéricos pueden ser útiles para fortalecer políticas de acceso a terapia anti-retroviral combinada (TARc). Objetivo: Describir la efectividad y seguridad del esquema genérico lamivudina/tenofovir/efavirenz (3TC/TDF/EFV) en pacientes con infección por VIH/SIDA naïve, pertenecientes a un programa de atención integral. Materiales/Métodos: Estudio clínico prospectivo fase IV abierto y sin grupo control. Entre 2012-2014, se incluyeron y siguieron 40 pacientes con infección por VIH/SIDA naïve y con indicación para iniciar tratamiento. Los pacientes fueron tratados con el esquema genérico 3TC/TDF/EFV y fueron seguidos durante 12 meses. El seguimiento incluyó valoración clínica, parámetros inmunovirológicos y de laboratorio, al inicio del tratamiento y a los 3, 6 y 12 meses. Resultados: De los 40 pacientes, 30 (75%) cumplieron los doce meses de tratamiento; de ellos, 80% alcanzó CV indetectable (< 40 copias/mL) y 83,3% CV < 50 copias/mL. Adicionalmente, en el grupo hubo un incremento en la mediana de 173 linfocitos TCD4/mm3. Por su parte, los resultados del hemograma completo, creatininemia y transaminasas hepáticas se conservaron en rangos normales y no generaron cambios del TARc. Los efectos adversos reconocidos para estos medicamentos se presentaron en menos de 10% de los pacientes y no tuvieron implicaciones graves. Conclusiones: En este grupo pequeño de pacientes, el esquema genérico 3TC/TDF/EFV es efectivo y seguro en el tratamiento de pacientes con infección por VIH/SIDA naïve, y su perfil de efectividad y seguridad es similar al del esquema 3TC/TDF/EFV innovador en pacientes con condiciones clínicas similares.

Background: Clinical studies aimed to evaluating the quality of generic drugs may be useful to strengthen policies of access to combined antiretroviral therapy (cART). Aim: To describe the effectiveness and safety of the generic schema lamivudine/tenofovir/efavirenz (3TC/TDF/EFV) in patients with HIV/AIDS naive, belonging to a comprehensive care program. Methods: A nonrandomized, open-label, phase IV study, during 2012 to 2014 naive HIV-infected patients 18 years or older with indication to receive cART were recruited. Patients were treated with generic scheme 3TC/TDF/EFV and were followed-up during 12 months. Clinical, immunological and laboratory parameters were assessed at baseline, 3, 6 and 12 months of treatment. Results: Of the 40 patients, 30 (75%) met the 12 months of treatment; of them, 80% achieved undetectable viral load (< 40 copies/mL) and 83.3% viral load < 50 copies/mL. Additionally, there was a significant increase (173 cells/mm3) in the median for CD4 T lymphocyte count. Moreover, the results of the whole blood count, creatinine and transaminases were preserved in normal ranges and did not generate changes in the cART. Potential side effects of antiretroviral drugs occurred in less than 10% of patients and had no serious implications. Conclusions: In this small group of patients, the generic scheme 3TC/TDF/EFV is effective and safe in the treatment of patients with HIV/AIDS naïve, and its effectiveness and safety profile is similar to show by innovator scheme 3TC/TDF/EFV in patients with similar clinical conditions. Registro Estudio: Registro Público Cubano de Ensayos Clínicos (RPCEC) ID: RPCEC00000134. Registered 20 July 2012.

Circulación de Klebsiella spp. multirresistente en un sanatorio privado de la ciudad de Resistencia, Chaco / Circulation of Klebsiella spp. multiresistant in a private sanatorium in the city of Resistencia, Chaco

El género Klebsiella tiene importancia en hospitales y sanatorios por su tendencia a causar brotes. Una característica sobresaliente es la resistencia natural y/o adquirida a antimicrobianos. Según la red WHONET - Argentina, existe circulación de Klebsiella en nosocomios, particularmente en salas de terapia intensiva. En este trabajo se evaluó la presencia de Klebsiella spp. en 1233 pacientes de un sanatorio de la ciudad de Resistencia (Chaco), durante el período 2015 ­ 2017. La detección de la bacteria se realizó por cultivo y la sensibilidad se determinó por difusión en agar. Se detectó Klebsiella en 5.6% (69) de las muestras y multirresistencia en 84% de los aislamientos. Se concluye que existe circulación de Klebsiella en la institución, debe ser correctamente identificada y establecido su nivel de resistencia. Esto es fundamental para disminuir los fracasos terapéuticos

The Klebsiella genus is important in hospitals and sanatoriums because of its tendency to cause outbreaks. An outstanding characteristic is the natural and / or acquired resistance to antimicrobials. According to the WHONET-Argentina network, there is Klebsiella circulation in hospitals, particularly in intensive care rooms. In this work, we searched Klebsiella spp. in 1233 patients from a sanatorium in the city of Resistencia (Chaco), during the period 2015 - 2017. The detection of the bacteria was carried out by culture and the sensitivity was determined by agar diffusion. Klebsiella was detected in 5.6% (69) of the samples and multiresistance in 84% of the isolates. It is concluded that there is Klebsiella circulation in the institution, it must be correctly identified and its level of resistance established. This is essential to reduce therapeutic failures