Resistencia transmitida de VIH-1 en pacientes sin exposición a tratamiento antirretroviral: Guatemala / Transmitted HIV-1 resistance in patients without exposure to antiretroviral treatment: Guatemala / Resistência transmitida ao HIV-1 em pacientes sem exposição ao tratamento antirretroviral: Guatemala

El objetivo del estudio fue describir los niveles de resistencia transmitida de VIH-1 en adultos atendidos en Unidades de Atención Integral de Guatemala. El estudio incluyó registros de 185 pacientes adultos VIH-1 positivo, de reciente diagnóstico sin antecedente de uso de TAR, de noviembre del 2019 a noviembre del 2020. El análisis se realizó en el software DeepChek® v2.0, para la clasificación de la resistencia se siguió el algoritmo de Stanford HIVdb (v9.4 - 07/12/2022). Se encontró 18.4% (IC 95% 13.1 - 24.7%) de resistencia general a alguna familia de ARVs. Se evidenció 15.1% (IC 95% 10.3 - 21.1%) de resistencia individual a la familia de INNTR afectando principalmente a NVP y EFV; 2.2% (IC 95% 0.6 - 5.4%) de resistencia a INTR, mayormente a FTC/3TC; y 2.7% (IC 95% 0.9 - 6.2%) de resistencia intermedia y baja los IP NFV y LPV/r. Tres casos presentaron resistencia múltiple a los INTR + INNTR. Las mutaciones más frecuentemente encontradas fueron K103N (41.2%), M184V/I (8.8%) y M46I (5.9%). La elevada resistencia transmitida del VIH-1 en pacientes atendidos en distintas Unidades de Atención Integral del VIH, demuestra la importancia de analizar periódicamente la tendencia de la resistencia en personas que no han estado expuestas a ARVs, lo cual a su vez es un marcador indirecto de presencia de resistencia adquirida en el país, datos que evidencian la necesidad de acciones e intervenciones prontas y efectivas dado su impacto en la salud pública.

The objective of this study was to describe the levels of transmitted HIV-1 resistance in patients with a recent HIV diagnosis before starting ART, treated in Comprehensive Care Units in Guatemala during the years 2019 and 2020. The study included records of 185 HIV-positive adult patients, recently diagnosed with HIV without a history of ART use. The analysis was carried out in the DeepChek® v2.0 software, the Stanford HIVdb algorithm (v9.4 - 07/12/2022) was followed to classify resistance. 18.4% (95% CI 13.1 - 24.7%) of general resistance to some family of ARVs was found. There was evidence of 15.1% (95% CI 10.3 - 21.1%) of individual resistance to the NNRTI family, mainly affecting NVP and EFV; 2.2% (95% CI 0.6 - 5.4%) resistance to INTR, mostly to FTC/3TC; and 2.7% (95% CI 0.9 - 6.2%) of intermediate and low resistance IP NFV and LPV/r. Three cases presented multiple resistance to NRTIs + NNRTIs. The most frequently found mutations were K103N (41.2%), M184V/I (8.8%) and M46I (5.9%). The high transmitted resistance of HIV-1 in patients treated in different Comprehensive HIV Care Units demonstrates the importance of periodically analyzing the trend of resistance in people who have not been exposed to ARVs, which in turn is an indirect marker. of the presence of acquired resistance in the country, data that demonstrate the need for prompt and effective actions and interventions given its impact on public health.

O objetivo deste estudo foi descrever os níveis de resistência transmitida ao HIV-1 em adultos tratados em Unidades de Cuidados Integrais na Guatemala. O estudo incluiu prontuários de 185 pacientes adultos HIV-1 positivos, recentemente diagnosticados sem histórico de uso de TARV, no período de novembro de 2019 a novembro de 2020. A análise foi realizada no software DeepChek® v2.0, para classificação da resistência, O algoritmo Stanford HIVdb (v9.4 - 07/12/2022) foi seguido. Foi encontrada 18.4% (IC 95% 13.1 - 24.7%) de resistência geral a alguma família de ARVs. Houve evidência de 15.1% (IC 95% 10.3 - 21.1%) de resistência individual à família de NNRTI, afetando principalmente NVP e EFV; 2.2% (IC 95% 0.6 - 5.4%) resistência ao INTR, principalmente ao FTC/3TC; e 2.7% (IC 95% 0.9 - 6.2%) de resistência intermediária e baixa ao IP NFV e LPV/r. Três casos apresentaram resistência múltipla a NRTIs + NNRTIs. As mutações mais frequentemente encontradas foram K103N (41.2%), M184V/I (8.8%) e M46I (5.9%). A elevada resistência transmitida do HIV-1 em pacientes atendidos em diferentes Unidades de Cuidados Integrados ao HIV demonstra a importância de analisar periodicamente a tendência de resistência em pessoas que não foram expostas aos ARVs, o que por sua vez é um marcador indireto da presença de ARVs adquiridos. resistência no país, dados que demonstram a necessidade de ações e intervenções rápidas e eficazes dado o seu impacto na saúde pública.

In vitro and in silico evaluation of antiretrovirals against SARS-CoV-2: A drug repurposing approach.

Background: Drug repurposing is a valuable strategy for rapidly developing drugs for treating COVID-19. This study aimed to evaluate the antiviral effect of six antiretrovirals against SARS-CoV-2 in vitro and in silico. Methods: The cytotoxicity of lamivudine, emtricitabine, tenofovir, abacavir, efavirenz and raltegravir on Vero E6 was evaluated by MTT assay. The antiviral activity of each of these compounds was evaluated via a pre-post treatment strategy. The reduction in the viral titer was assessed by plaque assay. In addition, the affinities of the antiretroviral interaction with viral targets RdRp (RNA-dependent RNA polymerase), ExoN-NSP10 (exoribonuclease and its cofactor, the non-structural protein 10) complex and 3CLpro (3-chymotrypsin-like cysteine protease) were evaluated by molecular docking. Results: Lamivudine exhibited antiviral activity against SARS-CoV-2 at 200 µM (58.3%) and 100 µM (66.7%), while emtricitabine showed anti-SARS-CoV-2 activity at 100 µM (59.6%), 50 µM (43.4%) and 25 µM (33.3%). Raltegravir inhibited SARS-CoV-2 at 25, 12.5 and 6.3 µM (43.3%, 39.9% and 38.2%, respectively). The interaction between the antiretrovirals and SARS-CoV-2 RdRp, ExoN-NSP10 and 3CLpro yielded favorable binding energies (from -4.9 kcal/mol to -7.7 kcal/mol) using bioinformatics methods. Conclusion: Lamivudine, emtricitabine and raltegravir showed in vitro antiviral effects against the D614G strain of SARS-CoV-2. Raltegravir was the compound with the greatest in vitro antiviral potential at low concentrations, and it showed the highest binding affinities with crucial SARS-CoV-2 proteins during the viral replication cycle. However, further studies on the therapeutic utility of raltegravir in patients with COVID-19 are required.

Acompanhamento do comportamento do HIV através de exames laboratoriais em portadora do vírus: relato de caso / Monitoring of HIV behavior through laboratory tests in a virus carrier: case report

O vírus da imunodeficiência humana é o agente etiológico da AIDS, doença crônica que destrói o sistema imunológico e é caracterizada pela baixa contagem de células TCD4, alta contagem de partículas virais no sangue e manifestações clínicas da doença. O diagnóstico se dá com o aparecimento de infecções oportunistas, que levam a contagem de TCD4 a níveis menores que 200 céls/mm³. Os exames laboratoriais para o diagnóstico do HIV foram os principais avanços para o início do tratamento, reduzindo a transmissão. Detecção de anticorpos, detecção de antígenos e amplificação do genoma do vírus são alguns dos exames laboratoriais utilizados para diagnóstico. Os dois principais biomarcadores são os exames de contagem de células TCD4, que verifica o sistema imune, e a quantificação de carga viral, que informa a quantidade de partículas virais, mostrando a progressão da infecção. Quanto maior a carga viral, maior o dano ao sistema imune. Uma carga viral indetectável é inferior a 50 cópias/mL, mas valores menores ou iguais a 200 cópias/mL também impedem a transmissão. Uma declaração de consenso afirma que Indetectável é igual a Intransmissível. Portanto, quando indetectável, a transmissão inexiste. O presente estudo relata e discute o caso clínico de uma paciente diagnosticada com HIV/AIDS aos 28 anos, que sobreviveu, apesar do diagnóstico tardio, e sob presença de doença oportunista com um grave grau de diminuição de células TCD4 (22 cél/mm³). Por meio do diagnóstico, introdução e adesão correta da terapia antirretroviral e monitorização de exames laboratoriais, conseguiu evitar a morte e ter uma vida semelhante à de um HIV negativo. Ultrapassou a expectativa de vida que na descoberta era de 10 anos, com uma qualidade de vida considerável, não sendo transmissora do vírus, diminuindo assim o estigma e preconceito. O biomédico é peça fundamental nesse contexto, considerando que deve fornecer informações precisas e fidedignas, tão necessárias ao acompanhamento de pessoas vivendo com HIV, para que autoridades e profissionais de saúde adotem medidas adequadas, tanto na prevenção, quanto no diagnóstico e monitoramento da doença.

The human immunodeficiency virus is the etiological agent of AIDS, a chronic disease that destroys the immune system and is characterized by low TCD4 cell count, high viral particle count in blood and clinical manifestations of the disease. The diagnosis is due to the appearance of opportunistic infections, which lead to TCD4 counts below 200 cells / mm³. Laboratory tests for the diagnosis of HIV were the main advances in starting treatment, reducing transmission. Antibody detection, antigen detection and virus genome amplification are some of the laboratory tests used for diagnosis. The two main biomarkers are the TCD4 cell count tests, which checks the immune system, and viral load quantification, which reports the number of viral particles, showing the progression of infection. The higher the viral load, the greater the damage to the immune system. An undetectable viral load is less than 50 copies / mL, but values less than or equal to 200 copies / mL also prevent transmission. A consensus statement states that Undetectable equals Non-Transmissible. Therefore, when undetectable, transmission does not exist. The present study reports and discusses the clinical case of a patient diagnosed with HIV / AIDS at age 28, who survived despite late diagnosis and under the presence of opportunistic disease with a severe degree of TCD4 cell reduction (22 cells / mm³). Through the diagnosis, introduction and correct adherence of antiretroviral therapy and monitoring of laboratory tests, she was able to avoid death and have a life similar to that of an HIV negative. Exceeded the life expectancy that in the discovery was 10 years, with a considerable quality of life, not transmitting the virus, thus reducing the stigma and prejudice. The biomedical is a key player in this context, considering that he must provide accurate and reliable information, which is so necessary for the monitoring of people living with HIV, so that authorities and health professionals adopt appropriate measures, both in prevention, diagnosis and monitoring of the disease.

A oferta pública de medicamentos para aids e o papel de Farmanguinhos / Public supply of AIDS drugs and the role of Farmanguinhos

Resumo Este artigo descreve e analisa a participação do Instituto de Tecnologia em Fármacos (Farmanguinhos) na produção local de medicamentos antirretrovirais no Brasil. São também apresentadas as mudanças no padrão de provimento, a situação das parcerias para o desenvolvimento produtivo e a posição dos produtores nacionais para esses medicamentos. As estratégias metodológicas foram revisão bibliográfica, análise de documentos oficiais e dados fornecidos por Farmanguinhos e pelo Departamento de Condições Crônicas e Infecções Sexualmente Transmissíveis do Ministério da Saúde, via Lei de Acesso à Informação. Este artigo mostra que o estabelecimento das parcerias abriu novas perspectivas para o desenvolvimento da política de oferta pública de antirretrovirais para as pessoas vivendo com HIV, por contribuir para a sustentabilidade das despesas financeiras do Ministério da Saúde com medicamentos. Farmanguinhos é o laboratório público que fornece mais quantidades e recebe os maiores valores provenientes do fornecimento desses produtos ao Ministério da Saúde. Embora os medicamentos importados preponderem largamente em quantidade e valores pagos pelo Ministério da Saúde, Farmanguinhos permanece sendo um provedor fundamental na produção local de antirretrovirais. Apesar dos problemas verificados nas Parcerias, os ganhos nas competências tecnológicas na produção de antirretrovirais podem ampliar o horizonte tecnológico e produtivo do laboratório.

Abstract This article describes and analyses the part played by the Instituto de Tecnologia em Fármacos (Farmanguinhos) in local production of antiretroviral medicines in Brazil, as well as changes in the pattern of supply, the status of related Production Development Partnerships and the position of Brazilian producers of these medicines. The methodological strategies used were literature review and analysis of official documents and data provided by Farmanguinhos and by the Ministry of Health's Department of Chronic Conditions and Sexually Transmitted Infections, via the Information Access Law. This article shows that, by contributing to the sustainability of Ministry of Health expenditure on medicines, these partnerships have opened new prospects for developing the policy of public supply of antiretrovirals for people living with HIV. Farmanguinhos is the public laboratory that supplies the largest quantities of these products to the Ministry of Health and receives the largest revenues from supplying them. Although the imported medicines supplied to the Ministry of Health account for much larger quantities and revenues, Farmanguinhos continues to be a fundamentally important supplier of locally produced antiretrovirals. Despite the problems found in establishing the partnerships, the gains in antiretroviral production technology competences can broaden the laboratory's technological and production horizons.

Saúde mental, resiliência, religiosidade/espiritualidade e adesão à terapia antirretroviral em pessoas vivendo com HIV/aids / Mental health, resilience, religiosity/spirituality and adherence to antiretroviral therapy in people living with HIV/AIDS

A infecção por HIV/aids continua a representar um problema mundial de saúde pública. Durante as últimas décadas, a Terapia Antirretroviral (TARV) levou a uma diminuição relevante da morbi-mortalidade relacionada à doença. Para aprimoramento da adesão à TARV e, por consequência, da qualidade de vida das pessoas vivendo com HIV/aids (PVHA), a resposta à epidemia deve combinar intervenções biomédicas e também de saúde mental. Diante desse panorama, o objetivo geral desta Tese foi investigar as associações entre saúde mental, resiliência, religiosidade/espiritualidade (R/E) e adesão à TARV em PVHA. A partir de duas revisões integrativas de literatura, foi evidenciado que a R/E é uma dimensão psicossocial que pode ser preditora da adesão à TARV, assim como a resiliência. Contudo, poucos estudos avaliaram essas dimensões em PVHA e, principalmente, sua relação com a adesão. Posteriormente, foram realizados três estudos empíricos com 237 PVHA atendidas em um serviço de referência para doenças infecciosas de uma cidade de médio porte de Minas Gerais, Brasil, utilizando os seguintes instrumentos: (a) Questionário estruturado para a caracterização dos participantes; (b) Escala de Depressão, Ansiedade e Estresse - DASS-21; (c) Escala de Avaliação de Resiliência - EAR; (d) Índice de Religiosidade de Duke - DUREL; (e) Spirituality Self Rating Scale - SSRS e (e) Questionário para a avaliação da adesão ao tratamento antirretroviral - CEAT-VIH. O primeiro estudo foi descritivo, com o objetivo de conhecer o perfil de PVHA em termos do acesso aos cuidados do HIV, da adesão à TARV e da saúde mental durante a pandemia da COVID-19, enquanto o segundo e o terceiro trabalho foram inferenciais, com o objetivo de investigar os fatores associados à adesão à TARV e à saúde mental das PVHA, respectivamente. O perfil predominante foi de mulheres (51,5%), com idade média de 46,9 anos (DP + 12,2), pessoas pretas e pardas (67%), com baixa renda familiar (65,4%), baixa escolaridade (62,8%), CD4 maior que 500 cels/mm³ (59,9%) e carga viral indetectável (82,3%). Foram considerados aderentes 72,6% dos entrevistados e 33,3% apresentaram adoecimento emocional. Os resultados evidenciaram que o valor do CD4, o fator de competência pessoal avaliado pela escala de resiliência e o uso de bebidas alcoólicas nos últimos seis meses tiveram um impacto positivo sobre a adesão, enquanto que a maior frequência do uso de bebidas alcoólicas, o uso de drogas ilícitas, a carga viral detectável e sintomas de ansiedade aumentaram as chances da não adesão. Já a satisfação com a imagem corporal, o apoio social dirigido a questões emocionais, o fator de resiliência de persistência diante das dificuldades, a religiosidade não organizacional e a presença de morbidades tiveram um impacto positivo sobre a saúde mental, enquanto que o uso de drogas ilícitas, ser mulher, o estresse vivenciado na pandemia pela COVID-19 e o uso de medicações psiquiátricas aumentaram as chances de adoecimento emocional. Esses achados podem contribuir para o planejamento e a implementação de intervenções baseadas em evidências nos serviços de saúde para o aprimoramento da adesão aos antirretrovirais e cuidado em saúde mental das PVHA, com destaque para os fatores protetivos em saúde representados pela R/E e pela resiliência.

The HIV/AIDS infection continues to represent a global public health problem. Over the past decades, Antiretroviral Therapy (ART) has led to a significant decrease in morbidity and mortality related to the disease, in addition to affecting the transmission of the virus by means of its suppression. These benefits, however, require adherence to treatment. To improve adherence and, consequently, the quality of life of people living with HIV/AIDS (PLWHA), the response to this epidemic must combine biomedical and mental health interventions. Given this scenario, the overall objective of this thesis was to investigate the associations between mental health, resilience, religiosity/spirituality (R/S) and adherence to ART in PLWHA. Based on two integrative literature reviews, it was evidenced that R/S is a psychosocial dimension that can be a predictor of adherence to ART, as well as resilience. However, few studies have assessed these dimensions in PLWHA and, particularly, their association with adherence. Subsequently, three empirical studies were conducted with 237 PLWHA treated in a renown service for infectious diseases in a medium-sized city in the countryside of Minas Gerais, Brazil, using the following instruments: (a) Structured questionnaire for the characterization of the participants; (b) Depression, Anxiety and Stress Scale - DASS-21; (c) Resilience Appraisal Scale - RAS; (d) Duke University Religion Index - DUREL; (e) Spirituality Self Rating Scale - SSRS and (e) Questionnaire for the assessment of adherence to antiretroviral treatment - CEAT-VIH. The first study was descriptive, aiming to know the profile of PLWHA in terms of their access to HIV care, ART adherence and mental health during the pandemic of COVID-19, while the second and third studies were inferential, aiming to investigate the factors associated with ART adherence and mental health of PLWHA, respectively.The predominant profile was of women (51.5%), mean age 46.9 years (SD + 12.2), black and brown people (67%), with low family income (65.4%), low education (62.8%), CD4 greater than 500 cells/mm³ (59.9%) and undetectable viral load (82.3%). Were considered adherent 72.6% of the interviewees and 33.3% showed emotional distress. The results showed that the CD4 value, the personal competence factor appraised by the resilience scale, and the use of alcoholic beverages in the last six months had a positive impact on adherence, while the higher frequency of alcoholic beverages use, use of illicit drugs, detectable viral load, and anxiety symptoms increased the chances of non-adherence. On the other hand, satisfaction with body image, social support directed to emotional issues, resilience factor, persistence in the face of difficulties, non-organizational religiosity and the presence of morbidities had a positive impact on mental health, while the use of illicit drugs, being a woman, the stress experienced in the COVID-19 pandemic and the use of psychiatric medications increased the chances of emotional illness. These findings may contribute to the planning and implementation of evidence-based interventions in health services to improve antiretroviral adherence and mental health care for PLWHA, with emphasis on the protective health factors represented by R/S and resilience.

Efectividad y seguridad de antirretrovirales para terapia de cambio en virus de la inmunodeficiencia humana

RESUMEN Introducción: El aumento de la expectativa de vida en personas que viven con VIH ha obligado a buscar alternativas de terapia antiretroviral simplificadas y con menor potencial de toxicidad que favorezcan la adherencia, y con ello alcanzar metas de indetectabilidad de la carga viral. Varias alternativas se han propuesto en los últimos años y es necesario saber la efectividad de estas a mediano y largo plazo. Objetivo: Determinar la efectividad y seguridad de la terapia de cambio, en pacientes mayores a 12 años que viven con el virus de la inmunodeficiencia humana. Métodos: Se realizó la búsqueda de la literatura en bases de datos electrónicas y literatura gris. La medida de desenlaces para mantenimiento de carga viral (menos de 50 copias por mililitro), niveles de linfocitos T CD4+ y eventos adversos de la terapia de cambio frente a continuación de la terapia estándar se estimó de forma combinada. Resultados: Se incluyeron seis ensayos clínicos aleatorizados que compararon terapia de cambio (Rilpivirina/Emtricitabina/Tenofovir alafenamida, Dolutegravir/Rilpivirina, Abacavir/Dolutegravir/Lamivudina), frente a la continuación de la terapia estándar. El mantenimiento de la carga viral no fue diferente entre los grupos (OR: 0,77; IC95% 0,59; 1,02), tampoco el recuento de linfocitos T CD4+ (DME: 6;76; IC95% -5,05;18,57), al igual que los eventos adversos serios (OR: 1,03; IC95% 0,74; 1,42). Conclusiones: No se encontró diferencia en la efectividad y seguridad de la terapia de cambio frente a continuar la terapia estándar. Los resultados apoyan en uso de estas estrategias terapéuticas para favorecer la adherencia a la terapia antirretroviral.

ABSTRACT Introduction: Increase in the life expectancy of people living with HIV has led to the search for simplified antiretroviral therapy alternatives of lower toxicity potential which foster adherence and thus contribute to achieve viral load undetectability goals. Several options have been proposed in recent years, and it is necessary to be aware of their mid- and long-term effectiveness. Objective: Determine the effectiveness and safety of switch therapy in patients aged over 12 years who live with the human immunodeficiency virus. Methods: A bibliographic search was conducted in electronic databases and the gray literature. Combined estimation was made of the measure of outcomes for viral load maintenance (less than 50 copies per milliliter), CD4+ T lymphocyte levels and adverse events of switch therapy versus continuing standard therapy. Results: Six randomized clinical trials were included which compared switch therapy (rilpivirine / emtricitabine / tenofovir alafenamide, dolutegravir / rilpivirine, abacavir / dolutegravir / lamivudine) with continuing standard therapy. Viral load maintenance was not different between the groups (OR: 0.77; CI 95% 0.59, 1.02), nor was there any difference in the CD4+ T lymphocyte count (DME: 6.76; CI 95% -5.05;18.57) or the serious adverse events (OR: 1.03; CI 95% 0.74; 1.42). Conclusions: Differences were not found in the effectiveness and safety of switch therapy versus continuing standard therapy. Results support the use of these therapeutic strategies to foster adherence to antiretroviral therapy.

Prevalencia y patrones de resistencia adquirida a antirretrovirales en menores de 18 años en el Hospital de Especialidades Pediátricas "Omar Torrijos Herrera" / Prevalence and patterns of acquired resistance to antiretrovirals in children under 18 years of age

Introducción: La resistencia a antirretrovirales compromete la efectividad del tratamiento de pacientes con infección por VIH, llevando a falla virológica e inmunológica, deterioro clínico y comprometiendo tratamientos futuros. Los niños y adolescentes tienen mayor riesgo de desarrollo de resistencia asociados a terapias prolongadas, mala adherencia y limitadas opciones terapéuticas. Se desconoce la prevalencia y patrones de resistencia adquirida en población pediátrica panameña. Objetivos: Conocer la prevalencia y describir los patrones de resistencia adquirida en población pediátrica infectada con falla virológica en el período 2009-2019 Material y Método: Estudio descriptivo. Se incluyeron sujetos menores de 18 años de edad, con al menos un año de tratamiento, en falla virológica y que contaban con una prueba de genotipaje. Se realizó revisión de los expedientes clínicos para la obtención de los datos. Se describen las características demográficas, historial de tratamiento, resistencia a familias de antirretrovirales y mutaciones específicas Resultados y conclusiones: 13 pacientes fueron incluidos en el estudio de un total de 72 pacientes con infección de VIH atendidos en el período de estudio, para una prevalencia de resistencia del 18% de sujetos en terapia con resistencia. Se encontró 92% de resistencia a Inhibidores de la transcriptasa reversa análogo de nucleósidos, 61.5% a inhibidores de la transcriptasa reversa no análogos de nucleósidos y 23% de resistencia a Inhibidores de proteasa, las mutaciones M184V y K103N fueron las más frecuentes. Se requiere mantener la vigilancia de resistencia en niños con el fin de ajustar las recomendaciones de tratamiento.

Introduction: Antiretroviral resistance compromises the effectiveness of the treatment of patients with HIV infection, leading to virological and immunological failure, clinical deterioration and compromising future treatments. Children and adolescents are at increased risk of developing resistance associated with prolonged therapies, poor adherence, and limited therapeutic options. The prevalence and patterns of acquired resistance in the Panamanian pediatric population are unknown. Metodology Descriptive study. Subjects under 18 years of age, with at least one year of treatment, in virological failure and who had a genotyping test were included. A review of the clinical records was carried out to obtain the data. Demographic characteristics, treatment history, and at the time of genotyping, resistance to antiretroviral families and specific mutations are described. Conclusions: 13 patients were included in the study of a total of 72 patients with HIV infection attended in the study period, for a prevalence of 18% of subjects on antirretroviral therapy. It was found 92% resistance to nucleoside reverse transcriptase inhibitor, 61.5% to non- nucleoside reverse transcriptase inhibitor and 23% resistance to protease inhibitor. The M184V and K103N mutation were the most frequent. Surveillance of ARV resistance in children is required to adjust treatment recommendations.

Nível de estresse entre jovens vivendo com HIV em tratamento: estudo descritivo-exploratório / Stress level among young people living with HIV undergoing treatment: a descriptive-exploratory study / Nivel de estrés en jóvenes con VIH en tratamiento: estudio descriptivo-exploratorio

OBJETIVO: averiguar o nível de estresse dos jovens vivendo com HIV em tratamento. MÉTODO: estudo descritivo-exploratório, de abordagem quantitativa, realizado com jovens vivendo com HIV que recebem tratamento no Serviço de Assistência Especializada de um hospital de referência para doenças infectocontagiosas. A coleta de dados ocorreu a partir de formulários compostos por questões sociodemográficas e o instrumento de avaliação do estresse: O Inventário de Sintomas de Stress. RESULTADOS: identificou-se que a maioria dos jovens vivendo com HIV possuem estresse, do tipo psicológico encontrando-se na fase de resistência. DISCUSSÃO: o fato de conviver com a sorologia e a terapia antirretroviral pode ser um fator preditor para manifestação de estresse. CONCLUSÃO: recomenda-se a implementação de ações que ultrapassem os danos físicos a fim de prevenir o adoecimento mental no curso do tratamento do HIV.

OBJECTIVE: to determine the stress level of young people living with HIV undergoing treatment. METHOD: a descriptive and exploratory study with a quantitative approach, conducted with young people living with HIV undergoing treatment in the Specialized Care Service of a reference hospital for infectious-contagious diseases. Data collection occurred from forms composed of sociodemographic questions and the following stress assessment instrument: the Stress Symptoms Inventory. RESULTS: it was identified that most of the young people living with HIV suffer from stress, of the psychological type in the resistance phase. DISCUSSION: the fact of living with the serology and the antiretroviral therapy can be a predictor for the manifestation of stress. CONCLUSION: it is recommended to implement actions that go beyond the physical harms in order to prevent mental illness in the course of HIV treatment.

OBJETIVO: conocer el nivel de estrés de los jóvenes que viven con VIH y están en tratamiento. MÉTODO: estudio descriptivo-exploratorio, con abordaje cuantitativo, realizado con jóvenes que viven con VIH y que reciben tratamiento en el Servicio de Atención Especializada de un hospital de referencia en enfermedades infectocontagiosas. La recolección de datos se realizó mediante formularios compuestos por preguntas sociodemográficas y el instrumento de evaluación del estrés: el Inventario de Síntomas de Estrés. RESULTADOS: se identificó que la mayoría de los jóvenes que vive con VIH tiene estrés, de tipo psicológico, y se encuentra en fase de resistencia. DISCUSIÓN: el hecho de convivir con serología y terapia antirretroviral puede ser un factor predictivo para la manifestación de estrés. CONCLUSIÓN: se recomienda implementar acciones que vayan más allá del daño físico para prevenir enfermedades mentales en el curso del tratamiento del VIH.

The 1G/1G+1G/2G Genotypes of MMP1 rs1799750 Are Associated with Higher Levels of MMP-1 and Are Both Associated with Lipodystrophy in People Living with HIV on Antiretroviral Therapy.

In HIV-infected patients, antiretroviral therapy (ART) is associated to adipose tissue redistribution known as lipodystrophy (LD). This study aimed at verifying the association between the polymorphism of the MMP1 gene (rs1799750) (1G/2G) and the serum levels of matrix metalloproteinase 1 (MMP-1) with LD and its subtypes in people living with HIV on ART. This is a cross-secional study. LD was self-reported. The determination of the MMP1 rs1799750 gene polymorphism was performed by real-time PCR, and the serum concentrations of MMP-1 were quantified by the enzyme-linked immunosorbent assay (ELISA) method. Of 404 participants, 204 (51%) were diagnosed with LD, of whom 89 (43%) had mixed lipodystrophy (ML), 72 (35%) had lipohypertrophy (LH), and 43 (22%) had lipoatrophy (LA). There was an association between the genotypes 1G/1G+1G/2G and higher serum levels of MMP-1 (p = .025). There was no association of MMP1 (1G/2G) with LD. Other factors associated with LD were current CD4 ≤ 350 [odds ratio (OR) = 4.85, confidence interval (CI) = 1.78-47.99, p = .0033] and serum MMP-1 levels >6.81 (OR = 2.67, CI = 1.21-6.08, p = .0165). Factors associated with ML: current CD4 ≤ 350 (OR = 5.59, CI = 1.69-20.39, p = .006); with LH: number of antiretroviral regimens used: 2 (OR = 2.06, CI = 1.01-4.20, p = .0460) and 3+ (OR = 2.09, CI = 1.00-4.35, p = .0477), and current CD4 ≤ 350 (OR = 2.08, CI = 1.00-4.24, p = .0461); and with LA: current viral load >40 (OR = 2.52, CI = 1.03-5.91, p = .0372) and current use of zidovudine (OR = 2.97, CI = 1.32-6.54, p = .0074). Higher levels of MMP-1 were associated with genotypes 1G/2G+1G/1G and with LD. Other individual risk factors were independently associated with LD, and its subtypes, suggesting that the pathogenesis itself is differently manifested for each type of LD.

Osteonecrosis de la cabeza femoral e infección de VIH/sida en la epidemia de Cuba / Osteonecrosis of the femoral head and HIV/AIDS infection in the Cuban epidemic

Introducción: La osteonecrosis es un trastorno asociado al déficit de riego sanguíneo con isquemia en los vasos nutricios de los huesos interesados, causa dolor crónico y discapacidad funcional. Con el desarrollo de la epidemia de VIH, se aprecia un marcado incremento de esta afección. Objetivo: Determinar la frecuencia y caracterizar clínica y epidemiológicamente a los pacientes cubanos con VIH/sida que desarrollaron osteonecrosis. Métodos: Estudio analítico prospectivo de pilotaje en una serie de 285 pacientes adultos, con infección por HIV/sida atendidos en el Instituto de Medicina Tropical Pedro Kourí en la era posterior a la terapia antirretroviral (TARVAE), años 2003-2018. Los pacientes ofrecieron su consentimiento informado. Se evaluaron variables epidemiológicas consideradas factores de riesgo (estatus procoagulante, alcoholismo, tabaquismo, hipercolesterolemia e hiperlipidemia, consumo de esteroides, conteo de células T, CD4+ y drogas antirretrovirales). Resultados: La edad promedio de la serie fue de 41 años, con una supervivencia de 12 años, marcado predominio del sexo masculino y piel blanca. El modo de adquisición del VIH prevaleciente fue la vía sexual y de hombres que tienen sexo con hombres (67,3 por ciento). Tres pacientes desarrollaron osteonecrosis (1,05 por ciento), necrosis avascular de caderas (2 casos en la derecha y uno bilateral), con cambios radiográficos por esta afección. Entre los factores asociados, un paciente tenía hiperlipidemia, dos eran fumadores, uno consumía alcohol, y los tres tenían conteo de células T CD4+ de más de 200. Todos tenían instaurada la TARVAE con inhibidores de proteasas y de la transcriptasa inversa, incluido tenofovir. Conclusiones: En esta serie de 285 pacientes con VIH, hubo una baja frecuencia de osteonecrosis. No se establecieron relaciones causales entre los factores de riesgo reconocidos en la literatura, la TARVAE y la aparición de osteonecrosis. Queda por definir el papel desempeñado por la infección VIH per se en el desarrollo de esta complicación, o develar si existen otras variables no exploradas en este estudio(AU)

Introduction: Avascular Necrosis or Osteonecrosis (ON) is a process associated with the blood supply deficit with ischemia in the nutritional vessels of the interested bones determining chronic pain, functional disability. In recent years with the growing development of the HIV epidemic, a marked increase in this condition has been observed. Objective: To determine an characterize in the clinical and epidemiological order the Cuban HIV + patients, who developed ON in the context of the HIV epidemic in a series of 285 HIV + cases with highly effective ARV therapy including tenofovir. Methods: Prospective analytical pilot study in a series of 285 patients, with HIV-AIDS infection adults treated in the IPK of Cuba in the later era (years 2003-17) to high-efficiency ARV therapy (TARVAE). Patients diagnosed with HIV / AIDS who offered their informed consent to participate in the study were included, and the research was approved by the IPK Ethics Committee. Results: Average age 41 (15-71) years (p <0.05). Survival 12 years by studies of Kaplan and Maier. Marked male predominance with 230 (81 percent), 55 (19.2 percent) women, white skin color, and 50-59 age group with 146 (51.2 percent) (p <0.05); data similar to the rest of the Cuban population according to other COPCORD Epidemiological studies. (18) Sexual and HIVH prevalent HIV acquisition mode with 192 (67.3 percent). 154 (54 percent) had an undetectable viral load. We found 3 (1.05 percent) patients who developed ON, with an average age of 52 (40-61a), 2 patients in right hip, and one bilateral avascular necrosis of the hips, all with radiological changes of this condition. As associated FR, one patient had hyperlipidemia, another 2 smoker, and 1 alcohol, all 3 with CD4 + T cell count <200 And high viral load. All cases had TARVAE with protease inhibitors, and reverse transcriptase, including Tenofovir. Conclusions: Our report is aimed at showing a low frequency of ON in our series of 285 patients studied in the Cuban HIV epidemic. The hips were the sites of ON, with 1 patients bilateral involvement. Hyperlipidemia, tabaquism and alcohol were the principal risk factors presented and low level of CD4 + T cels, and high viral load. We were unable to establish causal relationships between the recognized risk factors reported in the literature, HAART and the appearance of ON, all of which leave the role played by HIV infection per se in the development of this complication, or the effects of other variables that we have not explored in this preliminary study(AU)

Perfil lipídico en pacientes HIV positivos con dos tratamientos antirretrovirales que acudieron al Programa Regional de control VIH- SIDA de la VII Región Sanitaria de Itapúa en el periodo abril a septiembre de 2016 / Lipid profile in HIV-positive patients with two antiretroviral treatments attending the Regional HIV-AIDS Control Programme of the VII Itapúa Health Region from April to September 2016

Numerosas investigaciones demuestran que existe alteración del metabolismo lipídico en pacientes con VIH/SIDA, caracterizada por un aumento en la concentración de triglicéridos y la disminución de las lipoproteínas de alta y baja densidad y del colesterol total. La dislipidemia en personas VIH/SIDA depende de la supresión viral en el momento del estudio, de la respuesta al agente antirretroviral específico que se relaciona con la susceptibilidad genética, además de otros factores entre los cuales se encuentra el empleo de medicamentos, el peso y el estilo de vida. Los pacientes que conviven con esta infección tienen por esta razón un riesgo incrementado de accidente cardiovascular y diabetes. El objetivo fue determinar si existían diferencias en el perfil lipídico en una cohorte de pacientes que reciben esquemas de tratamientos diferentes en la población enfocada. Este fue un diseño observacional de cohorte prospectivo (24) con componente analítico que incluyó pacientes con diagnóstico de HIV y con tratamiento que concurrieron al Programa Regional de Control VIH-SIDA en el Hospital Regional de Encarnación-VII Región Sanitaria de Itapúa de abril a septiembre de 2016. Se encontraron diferencias significativas en la mayoría de los analitos componentes del perfil lipídico. Es necesario realizar un control periódico del perfil lipídico en estos grupos de pacientes, pues ello contribuirá a un mejor seguimiento del estado de salud así como a la prevención de accidentes cardiovasculares en los pacientes que conviven con VIH/SIDA y que están en tratamiento con antirretrovirales

Numerous research studies show that there is an impaired lipid metabolism in patients with HIV/AIDS, characterized by an increase in triglyceride concentration and decreased high- and low-density lipoproteins and total cholesterol. Dyslipidemia in HIV/AIDS people depends on viral suppression at the time of the study, response to the specific antiretroviral agent that relates to genetic susceptibility, as well as other factors including the use of medications, weight and lifestyle. Therefore, patients living with this infection have an increased risk of cardiovascular accident and diabetes. The objective was to determine whether there were differences in lipid profile in a cohort of patients receiving different treatment schemes in the targeted population. This was a prospective cohort design research with analytical component that included patients with HIV diagnosis and treatment that attended the Regional HIV-AIDS Control Programme at the Regional Hospital of Encarnacion - VII Itapúa Health Region from April to September 2016. Significant differences were found in most analytes components of the lipid profile. A periodic control of the lipid profile is necessary in these patient groups as this will contribute to a better monitoring of the health status as well as to the prevention of cardiovascular accidents in patients living with HIV/AIDS, and who are being treated with antiretrovirals

Adherencia al tratamiento antirretroviral en personas con VIH/sida de la región Caribe - colombiano

RESUMEN Introducción: A mediados de 2017, 20,9 millones de personas estaban recibiendo terapia antirretrovírica en todo el mundo. Sin embargo, solo 53 % de los 36,7 millones de personas que vivían con el VIH estaba recibiendo el tratamiento en 2016 a nivel mundial. Objetivo: Determinar adherencia al tratamiento antirretroviral de personas que conviven con VIH/sida. Métodos: Estudio cuantitativo, correlacional de corte transversal, en los meses de julio a octubre del 2019 en una muestra intencional de 166 personas con VIH/sida atendidas en institución de salud Santa Marta, Colombia. Para determinar adherencia se adaptó el instrumento Morisky-Green. Investigación sin riesgo según resolución 84 30 de 1993 del Ministerio de Salud y Protección Social de Colombia. Resultados: De 166 personas que conviven con VIH/sida, 74,7 % son hombres y 25,3 % son mujeres; la edad fluctúa entre una mínima 16 años y máxima73 años, con media de 39,3 años. El tiempo del tratamiento antirretroviral fue 6 años en promedio; 51,2 % utiliza alguna estrategia para acordarse de tomar los medicamentos; 68,1 % no fueron adherentes al tratamiento antirretroviral, 49,4 % hombres y 18,7 % mujeres. Se identificó que la relación médico-paciente es negativa (-0,005) y no está relacionada con la no adherencia. Conclusiones: La no adherencia al tratamiento antirretroviral estuvo representada por el 68,1 % de la población en estudio y es mayor en los hombres.

ABSTRACT Introduction: By mid-2017, 20.9 million people were under antiretroviral therapy worldwide. In 2016, only 53% of the 36.7 million people living with HIV worldwide were under treatment. Objective: Determine adherence to antiretroviral treatment among people living with HIV/AIDS. Methods: A quantitative cross-sectional correlational study was conducted from July to October 2019 of an intentional sample of 166 people with HIV/AIDS attending Santa Marta health center in Colombia. The Morisky-Green tool was adapted to determine adherence. The study was non-risk according to Resolution 84 30 / 1993 of the Ministry of Health and Social Protection of Colombia. Results: Of the total 166 people living with HIV/AIDS, 74.7% are men and 25.3% are women; mean age is 39.3 years (range 16-73). Average antiretroviral treatment duration is 6 years. 51.2% make use of some strategy to remember taking their medication; 68.1% are not adherent to antiretroviral treatment, 49.4% are men and 18.7% are women. The doctor-patient relationship was found to be negative (p = -0.005) and not related to non-adherence. Conclusions: Non-adherence to antiretroviral treatment was represented by 68.1% of the study population and is higher in men.

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).

Inhibidores de Transferencia de la Cadena de Integrasa: Bases para su uso en la práctica clínica / Integrase Strand Transfer Inhibitors: Bases for its use in the clinical practice

Los inhibidores de transferencia de la cadena de integrasa (INSTI) son medicamentos cuyo mecanismo de acción consiste en bloquear el proceso de integración del ADN proviral al ADN del hospedero mediante la unión al sitio catalítico de la integrasa viral y de esta manera evitar su replicación. Actualmente se cuenta con la aprobación INSTI de primera y segunda generación, presentan similitud en su mecanismo de acción, cambios en su estructura que modifican su barrera genética, pero mantienen su perfil de seguridad y efectividad. Desde su aprobación en el año 2007, se han llevado a cabo múltiples estudios clínicos cuyos resultados han permitido avanzar en el conocimiento de su efectividad en diferentes escenarios clínicos; (pacientes naive, experimentados, esquemas de simplificación y profilaxis, así, como en el conocimiento de su perfil de mutaciones de resistencia). En el presente artículo se hizo una revisión de los miembros de esta familia de antirretrovirales (ARV).

Integrase strand transfer inhibitors (INSTI) are drugs whose mechanism of action consists of blocking the integration process of the proviral DNA to the host DNA by binding to the catalytic site of the viral integration and thus preventing its replication. Currently it has the approval of INSTI of first generation, two of second generation and in process of approval of a third of second generation. The two generations has similitude in its mechanisms of action, changes in its structures that modify its genetic barrier, but keeping his security and effectiveness profile. Since the approval of INSTI´s in 2007 to date, multiple clinical studies have been carried out, whose results have allowed us to advance in the knowledge of their effectiveness in different clinical scenarios; (naive patients, experienced patients, simplification and prophylaxis schemes, as well as in the knowledge of their profile of resistance mutations). In the present article, we made a review of the members of this family of antiretrovirals (ARV).

Study of HIV Resistance Mutations Against Antiretrovirals using Bioinformatics Tools.

BACKGROUND: Antiretroviral drugs to HIV-1 (ARV) are divided into classes: Nucleotide Reverse Transcriptase Inhibitors (NRTIs); Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs); Protease Inhibitors (PIs); Integrase Inhibitors (INIs); fusion inhibitors and entry Inhibitors. The occurrence of mutations developing resistance to antiretroviral drugs used in HIV treatment take place in a considerable proportion and has accumulated over its long period of therapy. OBJECTIVE: This study aimed to identify resistance mutations to antiretrovirals used in the treatment of HIV-1 in strains isolated from Brazilian territory deposited at Genbank, as well as to relate to the clinical significance and mechanism of action. METHODS: Elucidation of these mutations was by comparative method of peptide sequence resulting from genes encoding therapeutic targets in HIV antiretroviral therapy (ART) of the strains with a reference sequence through bioinformatic genetic information manipulation techniques. RESULTS: Of the 399 sequences analyzed, 121 (30.3%) had some type of mutations associated with resistance to some class of antiretroviral drug. Resistance to NNRTIs was the most prevalent, detected in 77 (63.6%) of the 121 mutated sequences, compared to NRTIs and PIs, whose resistance was detected in 60 (49.6%) and 21 (17.3%), respectively, and to INIs, only 1 (0.8%) sample showed associated resistance mutation. CONCLUSION: Resistance to HIV ARV was detected at a considerable rate of 30.3%, showing some concerns about the percentage of viral strains that escape the established therapeutic regimen and that circulate currently in Brazil. The non-use of NNRTIs in Brazil is justified by the emergence of resistance mutations. The low prevalence of mutations against INIs is because drugs in this class have a high genetic barrier.

Calidad de vida y variables psicológicas que afectan la adherencia al tratamiento anti-retroviral en pacientes mexicanos con infección por VIH/SIDA / Quality of life and psychological variables affecting adherence to antiretroviral treatment in Mexican patients with HIV/AIDS

Resumen Introducción: El tratamiento anti-retroviral (TAR) es indispensable en pacientes con infección por VIH/ SIDA; suprimir la carga viral requiere de un estricto apego a éste, por compromiso del paciente. El fracaso del TAR es primordialmente por falta de adherencia, que puede ser debida a una deficiente calidad de vida y/o a variables psicológicas. Objetivo: Determinar la calidad de vida, variables psicológicas y la adherencia al TAR, en pacientes con infección por VIH/SIDA. Material y Método: Se incluyeron 160 pacientes con diagnóstico de infección por VIH/SIDA y con TAR. Se recabaron los instrumentos MOS SF-36 y VPAD-24, una encuesta demográfica, y datos clínicos. Se hicieron asociaciones cuantitativas y cualitativas entre las variables. Resultados: La adherencia al TAR estuvo asociada con evitar comportamiento depresivo y con ausencia de adicciones. El comportamiento depresivo se encontró asociado con las adicciones. Un 87% de pacientes estaba en el rango de mejor calidad de vida. Por debajo del promedio del puntaje de salud general estuvieron masculinos, con orientación sexual HSH, solteros, en la vitalidad a los ≥ 38 años, en dolor corporal y función social a tres esquemas TAR. Conclusión: La buena adherencia al TAR estuvo asociada a evitar comportamiento depresivo y a la ausencia de adicciones y no se asoció a la calidad de vida.

Background: Antiretroviral treatment (ART) is essential in HIV/AIDS patients. Suppressing viral load requires strict adherence to ART in addition to the patient's commitment to treatment. The failure of ART is mainly due to lack of adherence, which may in turn be due to poor quality of life and/or to psychological variables. Aim: To determine the quality of life and psychological variables and adherence to ART, in patients with HIV/AIDS. Material and Method: 160 patients diagnosed with HIV/AIDS and with ART were included. The MOS SF-36 and VPAD-24 instruments, a socio-demographic survey, and clinical data were collected. Quantitative and qualitative associations were made between the variables. Results: The adherence to ART was associated with avoidance of depressive behavior and with the absence of addictions. Depressive behavior associated with addictions. 87% of patients ranked in the best quality of life. Below the average of the general health score were males, with MSM sexual orientation, single, in vitality at ≥ 38 years, in corporal pain and with social function to three ART schemes. Conclusion: Good adherence to ART was associated with avoiding depressive behavior and with non-addictions and not associated with quality of life.

Reacciones adversas evitables graves por antivirales. Sistema Cubano de Farmacovigilancia, 2008-2017 / Serious adverse reactions avoidable by antivirals. Cuban Pharmacovigilance System, 2008-2017 / Reações adversas severas prevenidas por antivirais. Sistema cubano de farmacovigilancia, 2008-2017 / Réactions indésirables graves évitable par les antiviraux. Systeme cubain de pharmacovigilance, 2008-2017

Resumen Objetivo: Caracterizar las reacciones adversas graves evitables por antivirales presentes en el Sistema Cubano de Farmacovigilancia durante los años 2008 al 2017. Material y métodos: Investigación cuantitativa, observacional y descriptiva; enmarcada dentro de los estudios de farmacovigilancia, con un diseño de serie de casos. El universo conformado por las notificaciones de reacciones adversas graves evitables provocadas estos fármacos. Se utilizaron variables como: reacción adversa identificada, grupo de edad, sexo, fármaco antiviral, frecuencia y causas de evitabilidad. Resultados: Las reacciones adversas evitables graves a los antivirales se comportaron a ritmo irregular que muestra tendencia al incremento. Predominaron en hombres (77.8%) y en adultos (94.4%). Zidovudina (44.4%) y nevirapina (38.9%) muestraron la mayor cantidad de reportes, relacionados con la aparición de anemia y síndrome de Stevens Johnson. Los médicos reportaron el 72.2% de los casos. Las reacciones encontradas se describen como frecuentes. Las interacciones medicamentosas (61.1%) fue la principal causa de evitabilidad. Conclusiones: La caracterización de las reacciones adversas graves evitables a los antivirales permitió identificar que las mismas fueron frecuentes, producidas por antirretrovirales y presentadas hombres adultos; siendo la anemia y síndrome de Stevens Johnson las más frecuentes. Las causas de evitabilidad identificadas con mayor frecuencia responden a errores de la prescripción.

Abstract Object: To characterize the serious adverse reactions avoidable by antivirals present in the Cuban Pharmacovigilance System during the years 2008 to 2017. Materials and methods: Quantitative, observational and descriptive research; framed within the pharmacovigilance studies, with a case series design. The sample conformed by the reports of avoidable serious adverse reactions caused by these drugs. Variables were: identified adverse reaction, age group, sex, antiviral drug, frequency and causes of preventability. Results: Severe avoidable adverse reactions to antivirals were presented at an irregular level that shows a tendency to increase. They predominated in men (77.8%) and in adults (94.4%). Zidovudine (44.4%) and nevirapine (38.9%) showed the highest number of reports, related to the appearance of anemia and Stevens-Johnson syndrome. The doctors reported 72.2% of the cases. The reactions found are described as frequent. Drug interactions (61.1%) was the main cause of preventability. Conclusions: The characterization of the serious adverse reactions avoidable to the antivirals allowed to identify that they were in their majority produced by antiretroviral and occurred mainly in adult men; anemia and Stevens-Johnson syndrome were the most frequent. The causes of preventability identified with greater frequency correspond to errors of the prescription.

Resumo Objetivo: Saracterizar as reações adversas graves evitáveis por antivirais presentes no Sistema Cubano de Farmacovigiláncia durante os anos de 2008 a 2017. Materiais e métodos: Pesquisa quantitativa, observacional e descritiva; enquadrada no ámbito de estudos de farmacovigiláncia, com um desenho de estudos de casos. O universo foi constituido pelos relatórios das notificações de reações adversas graves causadas por esses medicamentos. Foram utilizadas variáveis, tais como: reacjao adversa identificada, grupo etário, sexo, fármaco antiviral, frequência e causas de prevenjao. Resultados: Reações adversas severas preveníveis por antivirais surgem a um ritmo irregular mostrando um aumento crescente. Predominaram em homens (77,8%) e em adultos (94,4%). Zidovudina (44,4%) e nevirapina (38,9%) apresentaram o maior número de relatos, relacionados ao aparecimento de anemia e síndrome de Stevens Johnson. Os médicos relataram 72,2% dos casos. As reações encontradas são descritas como frequentes. As interajoes medicamentosas (61,1%) foram a principal causa da prevenção. Conclusões: A caracterização de reações adversas graves, preveniveis por antivirais permitiram identificar que eram frequentes, produzidos por anti-retrovirais e apresentados em homens adultos; sendo a anemia e a síndrome de Stevens Johnson as mais frequentes. As causas mais frequentemente identificadas de prevenção demonstram erros de prescrição.

Résumé Objectif: Caractériser les effets indésirables graves évitables par les antiviraux présents dans le systéme cubain de pharmacovigilance pendant les années 2008 á 2017. Matériaux et méthodes: Recherche quantitative, observationnelle et descriptive; encadré dans les études de pharmacovigilance, avec une conception de série de cas. L'échantillon était conforme aux rapports d'effets indésirables graves évitables provoqués par ces médicaments. Les variables utilisées étaient réaction indésirable identifiée, groupe d'áge, sexe, médicament antiviral, fréquence et causes de prévention. Résultats: Les réactions indésirables évitables tombes aux antiviraux se sont comportées á un rythme irrégulier qui a tendance á augmenter. Ils prédominaient chez les hommes (77,8%) et chez les adultes (94,4%). La zidovudine (44,4%) et la névirapine (38,9%) présentaient le plus grand nombre de signalements, liés á l'apparition de l'anémie et au syndrome de Stevens-Johnson. Les médecins rapportent 72.2% des cas. Les réactions trouvées sont souvent déclinées. Les interactions médicamenteuses (61,1%) étaient la principale cause évitable. Conclusion: La caractérisation des effets indésirables graves évitables antiviraux a permis d'identifier qu'ils étaient produits principalement par les antirétroviraux et se produisaient principalement chez les hommes adultes; l'anémie et le syndrome de Stevens-Johnson étaient les plus fréquents. Les causes évitables identifiées généralement correspondent á des erreurs de prescription.

Enfoque de la diarrea en pacientes infectados con VIH / Approach to diarrhea in HIV patients

Resumen La diarrea es el síntoma gastrointestinal más frecuente en las personas infectadas por el virus de la inmunodeficiencia humana (VIH). La diarrea puede aparecer como consecuencia de infección por un germen oportunista, así como ser un efecto secundario del tratamiento antirretroviral. Esta, a su vez, puede ser aguda o crónica, esta última es la que causa mayor morbilidad y alteración en la calidad de vida del paciente. El enfoque diagnóstico se realiza por etapas que van desde una historia clínica completa hasta estudios microbiológicos, endoscópicos e imagenológicos. Finalmente, si se han descartado causas infecciosas u orgánicas (enteropatía idiopática), se debe brindar manejo al paciente en busca de aliviar los síntomas y optimizar la adherencia al tratamiento antirretroviral.

Abstract Diarrhea is the most common gastrointestinal symptom in people with human immunodeficiency virus infections. Diarrhea can appear to be a consequence of infection by an opportunistic germ or the side effect of antiretroviral treatment. It can be acute or chronic, but the latter leads to greater morbidity and alteration in patients' quality of life. Stages of the diagnostic approach range from taking a complete clinical history, to microbiological, endoscopic and imaging studies. Finally, if infectious or organic causes have been ruled out (idiopathic enteropathy), management provided to the patient should seek symptomatic relief and optimization of adherence to antiretroviral treatment.

Hollow mesoporous structured molecularly imprinted polymer as adsorbent in pipette-tip solid-phase extraction for the determination of antiretrovirals from plasma of HIV-infected patients.

In this work a hollow mesoporous structured molecularly imprinted polymer was synthetized and used as adsorbent in pipette-tip solid-phase extraction for the determination of lamivudine (3TC), zidovudine (AZT) and efavirenz (EFZ) from plasma of human immunodeficiency virus (HIV) infected patients by high-performance liquid chromatography (HPLC). All parameters that influence the recovery of the pipette tip based on hollow mesoporous molecularly imprinted polymer solid-phase extraction (PT-HM-MIP-SPE) method were systematically studied and discussed in detail. The adsorbent material was prepared using methacrylic acid and 4-vinylpyridine as functional monomers, ethylene glycol dimethacrylate as crosslinker, acetonitrile as solvent, 4,4'-azobis(4-cyanovaleric acid) as radical initiator, benzalkonium chloride as surfactant, 3TC, and AZT as templates. The simultaneous separation of 3TC, AZT and EFZ by HPLC-UV was performed using a Gemini C18 Phenomenex® column (250 mm × 4.6 mm, 5 µm) and mobile phase consisting of acetonitrile: water pH 3.2 (68:32, v/v), flow rate of 1.0 mL/min and λ = 260 nm. The method was linear over the concentration range from 0.25 to 10 µg/mL for 3TC and EFZ, and 0.05 to 2.0 µg mL-1 for AZT, with correlation coefficients larger than 0.99 for all analytes. Recovery ± relative standard deviations (RSDs %) were 41.99 ± 2.38%, 82.29 ± 1.63%, and 83.72 ± 7.52% for 3TC, AZT, and EFZ, respectively. The RSDs and relative errors (REs) were lower than 15% for intra and interday assays. The method has been successfully applied for monitoring HIV-infected patients outside the therapeutic dosage.

Prevalence of Drug Resistance Mutations in Protease, Reverse Transcriptase, and Integrase Genes of North Central Mexico HIV Isolates.

This study set out to determine the frequency of antiretroviral drug resistance mutations in treatment-naive subjects of the north central Mexican state of San Luis Potosí. Mexican studies of antiretroviral drug resistance mutations have focused mainly on large metropolitan areas and border towns subjected to intense international migrations. This study set forth to describe the frequency of these mutations in a Mexican region less subjected to such migratory influences and more representative of smaller Mexican cities. Thirty-eight full-length pol sequences spanning the protease, reverse-transcriptase, and integrase-encoding regions were obtained from 42 treatment-naive human immunodeficiency virus (HIV)-infected subjects. Most exhibited subtype B homology, but CRF02_AG was also detected. Evidence of APOBEC3 hypermutation was seen in two samples. Calibrated population analysis revealed a surveillance drug resistance mutation prevalence of 4.9% for protease inhibitors, of 2.7% for nucleoside reverse transcriptase inhibitors, of 8.1% for non-nucleoside reverse transcriptase inhibitors, and an overall prevalence of 9.5%. This corresponds to an intermediate level of transmitted drug resistance according to the World Health Organization. The identification of integrase mutations suggests that transmitted drug mutations are being imported, as inhibitors targeting integrase have not been widely used in Mexico. Our results provide a greater understanding of HIV diversity in Mexico and highlight the way internal migrations allow HIV mutations and genetic features to permeate regions less subjected to international migrations. The implications of these findings will become more evident as Mexico hosts increased repatriations of migrants in the coming years.