Identificación del alelo HLA B*57: 01 en una población militar, de Lima-Perú / Identification of the allele HLA B*57: 01 in a military population, from Lima-Peru

El alelo HLA B*57:01 es un marcador genético asociado con la hipersensibilidad al fármaco anti-retroviral abacavir (ABC) y su frecuencia en la población peruana todavía es desconocida. El objetivo fue identificar el alelo HLA B*57:01 en una población militar de Lima, Perú. Se reclutaron 43 personas viviendo con VIH (PVV) quienes aceptaron participar a través de un consentimiento informado. La detección del alelo HLA B*57:01 se realizó mediante RPC en tiempo real (RT-PCR). Asimismo, se determinó la carga viral (CV), el recuento de linfocitos CD4 y la genotipificación del VIH. Se identificaron dos casos positivos al alelo HLA B*57:01 (4,7%). Además, uno de ellos presentó múltiples mutaciones de resistencia a los anti-retrovirales (ARV), incluyendo ABC. Se demostró por primera vez en el Perú la presencia del alelo HLA B*57:01.

The HLA B*57:01 allele is a genetic marker associated with hypersensitivity to the antiretroviral Abacavir (ABC) and its frequency in the Peruvian population is still unknown. The objective was to identify the HLA B*57:01 allele in a military population from Lima, Peru. Forty three people living with HIV (PLWH) were recruited, who agreed to participate through informed consent. Detection of the HLA B*57:01 allele was performed by real-time PCR (RT-PCR). Likewise, viral load (VL), CD4 lymphocyte count and HIV genotyping were determined. Two cases positive for the HLA B*57:01 allele (4.7%) were identified. In addition, one of them had multiple resistance mutations to antiretrovirals (ARVs), including ABC. The presence of the HLA B*57:01 allele was demonstrated for the first time in Peru.

Situación epidemiológica de VIH a nivel global y nacional: Puesta al día / Epidemiological situation of HIV at global and national level: update

INTRODUCCIÓN: En las cuatro décadas de la epidemia por VIH, se han observado avances notables que han contribuido a una disminución progresiva en la incidencia de nuevas infecciones y en la mortalidad a nivel mundial. Sin embargo, no ha ocurrido lo mismo en Latinoamérica y en Chile. OBJETIVO: Esta revisión tiene como objetivo conocer la epidemiología actual a nivel global, latinoamericano y chileno. METODOLOGÍA: Se analizaron los informes epidemiológicos oficiales de infección por VIH emitidos por organismos nacionales e internacionales, más los estudios epidemiológicos nacionales. RESULTADOS: Se estima que 39 millones de personas viven con VIH en el mundo; no obstante, la mortalidad y la incidencia de nuevos casos han disminuido de forma notoria durante las últimas dos décadas, asociado a una expansión en al acceso a terapia antirretroviral en forma global. A diferencia del resto del mundo, América Latina presenta una tendencia de alza en las nuevas infecciones y Chile registra un aumento de 35% en nuevos casos durante los últimos 10 años, coincidiendo con un aumento en los flujos de migrantes que ha afectado a la región. Algunas estrategias preventivas como la profilaxis pre exposición se han implementa-do a un ritmo lento, tanto a nivel mundial, como latinoamericano. CONCLUSIONES: La epidemiología del VIH presenta características propias regionales y nacionales. En particular en Chile, diversos factores incluyendo déficit en políticas públicas de prevención y los recientes flujos migratorios han modelado nuestra actual epidemia. El desafío presente debe contemplar los esfuerzos multisectoriales para lograr los objetivos de ONUSIDA en esta década.

BACKGROUND: Over the course of the last four decades of global HIV epidemic, significant improvements have contributed to gradually reduce the frequency of new infections and global mortality rates. However, in Latin America particularly in Chile, new infections continue increasing. AIM: This review aims to comprehend the_epidemiology today on a worldwide, Latin American, and Chilean scale. METHODS: National epidemiology studies and official HIV reports from international and national organizations were reviewed. RESULTS: It is estimated that 39 million people live with HIV worldwide; however, mortality and the incidence of new cases have decreased markedly over the last two decades, associated with an expansion in access to antiretroviral therapy globally. In contrast to the rest of the world, Latin America shows an upward trend in new infections, with Chile registering a 35% increase in new cases over the last 10 years, coinciding with an increase in migratory flows that has occurred throughout the region. Some preventive strategies, such as pre-exposure prophylaxis, have been implemented at a slow pace, both globally and in Latin America. CONCLUSIONS: The epidemiology of HIV has regional and national characteristics. Specifically in Chile, several factors, including deficits in public prevention policies and recent migratory flows, have shaped our current epidemic. The present challenge must contemplate multisectoral efforts to achieve the UNAIDS objectives during this decade.

Avances en el tratamiento de los niños y adolescentes con infección por HIV / Advances in the treatment of children and adolescents with HIV infection

El uso de antirretrovirales (ARV) en el embarazo, el parto y el recién nacido y la aplicación de tratamientos combinados en los niños se han asociado con una disminución del sida en pediatría y el aumento de la sobrevida. La introducción de los inhibidores de integrasa en una dosis diaria ha eliminado barreras para la adherencia, pero los medicamentos orales diarios continúan planteando problemas de privacidad y estigma. Las nuevas tecnologías de administración de los medicamentos y las nuevas drogas junto con la combinación de ARV y los anticuerpos ampliamente neutralizantes (bNAb), ofrecen un potencial de opciones futuras para el tratamiento pediátrico del HIV. Los bNAb son anticuerpos que pueden reconocer diferentes tipos de HIV, bloquear su entrada en las células sanas y ayudar a destruir las células ya infectadas, pueden administrarse por vía parenteral y constituyen un enfoque novedoso y seguro con potencial para el tratamiento y la prevención del HIV, incluida la transmisión vertical. En los lactantes que contraen HIV, los bNAb podrían ofrecer ventajas terapéuticas al reducir el reservorio del virus, mejorar la inmunidad adquirida y, en el futuro, proporcionar un camino hacia la cura funcional. Dentro de los ARV inyectables de acción prolongada, cabotegravir/ rilpivirina se ha incorporado en las guías internacionales de adultos y adolescentes tanto para el tratamiento como para la prevención. A medida que el tratamiento del HIV en adultos va evolucionando, es fundamental asegurar que los neonatos, lactantes, niños y adolescentes tengan acceso a las mejores opciones de tratamiento y prevención a lo largo de su vida (AU)

The use of antiretrovirals (ARVs) during pregnancy, delivery, and in the newborn and the use of combination therapy in children have been associated with a decrease in pediatric AIDS and increased survival. The introduction of once-daily integrase inhibitors has removed barriers to adherence, but daily oral medications continue to pose privacy and stigma issues. New drug delivery technologies and new drugs along with the combination of ARVs and broadly neutralizing antibodies (bNAbs) offer potential future options for pediatric HIV treatment. bNAbs are antibodies that can recognize different types of HIV, block their entry into healthy cells and help destroy already infected cells, can be delivered parenterally, and represent a novel and safe approach with potential for the treatment and prevention of HIV, including mother-to-child transmission. In infants who contract HIV, bNBAs could offer therapeutic advantages by reducing the viral reservoir, enhancing acquired immunity and, in the future, providing a pathway to a functional cure. Within the long-acting injectable ARVs, cabotegravir/rilpivirine has been incorporated into international guidelines for adults and adolescents for both treatment and prevention. As adult HIV treatment evolves, it is critical to ensure that newborns, infants, children and adolescents have access to the best treatment and prevention options throughout their lives (AU)

Resistencia a los inhibidores de la integrasa en niños con el virus de la inmunodeficiencia humana por transmisión vertical: primeros casos en Uruguay / Resistance to integrase inhibitors in children with vertically-transmitted human immunodeficiency virus: First cases in Uruguay

La resistencia a los antirretrovirales (ARV) es un problema de salud pública. Con el uso de inhibidores de la integrasa (INSTI) en pediatría, también comienzan a aparecer resistencias. El objetivo de esta comunicación es describir 3 casos con resistencia a los INSTI. Se describen 3 pacientes pediátricos con transmisión vertical del virus de la inmunodeficiencia humana (VIH). Iniciaron ARV de lactantes y preescolares, con mala adherencia al tratamiento, cursaron con diferentes planes secundarios a comorbilidades asociadas y fallas virológicas por resistencia. Los 3 casos clínicos describen la rápida aparición de resistencia frente a la falla virológica y el compromiso de los INSTI. La adherencia debe ser supervisada para detectar precozmente el aumento de la viremia. La falla virológica en un paciente tratado con raltegravir obliga a un rápido cambio de esquema ARV, ya que continuar utilizándolo podría favorecer nuevas mutaciones y resistencia a los INSTI de segunda generación.

Antiretroviral (ARV) drug resistance is a public health issue. Resistance has also been observed in the case of integrase strand transfer inhibitors (INSTIs) used in pediatrics. The objective of this article is to describe 3 cases of INSTI resistance. These are the cases of 3 children with vertically-transmitted human immunodeficiency virus (HIV). They were started on ARVs as infants and preschoolers, with poor treatment adherence, and had different management plans due to associated comorbidities and virological failure due to resistance. In the 3 cases, resistance developed rapidly as a result of virological failure and INSTI involvement. Treatment adherence should be monitored so that any increase in viremia can be detected early. Virological failure in a patient treated with raltegravir forces to a rapid change in ARV therapy because its continued use may favor new mutations and resistance to second-generation INSTIs.

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.

HIV with initial ocular Kaposi sarcoma / HIV com sarcoma de Kaposi ocular inicial

ABSTRACT We present an interesting case of a 62-year-old black female, presented to the ophthalmological hospital with a little "nevus" on the left eye previously visualized at the mirror, with one month of development. Physical examination with slit lamp (biomicroscopy) showed a group of painless veins, with vascular redness, and a mass nodular aspect in the mid temporal bulbar conjunctiva, of approximately 2mmx4mm.

RESUMO Apresentamos o interessante caso de uma mulher negra de 62 anos, que deu entrada no hospital oftalmológico com um pequeno nevo no olho esquerdo previamente visualizado ao espelho, com 1 mês de evolução. O exame físico com lâmpada de fenda (biomicroscopia) mostrou um grupo de veias indolor e vermelhidão vascular, com uma massa de aspecto nodular na conjuntiva bulbar temporal média, de aproximadamente 2mmx4mm.

Resistencia genotípica del HIV a los antirretrovirales en niños de Argentina entre 2006 y 2021 / HIV genotypic drug resistance to antiretrovirals in children in Argentina between 2006 and 2021

Introducción: La resistencia del HIV a los antirretrovirales (ARVs) es una de las principales causas de fallo terapéutico en niños, niñas y adolescentes que conviven con el virus. Desde el año 2006, el Laboratorio de Biología Celular y Retrovirus del Hospital Garrahan realiza el estudio genotípico de resistencia (ER) del HIV-1 a los ARVs a fin de identificar mutaciones que disminuyen la susceptibilidad del virus a los fármacos que componen el tratamiento ARV. Objetivos: El objetivo del trabajo fue estudiar el tipo y frecuencia de resistencia del HIV a los ARVs, a través de un análisis de 371 ER realizados entre los años 2006 y 2021 en niños, niñas y adolescentes con HIV-1 adquirido por transmisión vertical y con solicitud médica de ER por presentar fallo terapéutico. Resultados: Entre los años 2006 y 2013 la proporción de casos con resistencia a al menos una clase de fármaco ARV fue mayor al 90%, sugiriendo una asociación directa entre el fallo virológico y la disminución en la susceptibilidad del HIV-1 a uno o más componentes del TARV. A partir del año 2012, se observa una disminución progresiva del nivel de resistencia de HIV-1, llegando al 50% en 2021 (p<0.0001). La frecuencia de mutaciones de resistencia fue diferente para cada una de las clases de ARVs. Mientras que la resistencia a INNTR no sufrió cambios significativos a lo largo del período de estudio, oscilando entre 27% y 75%. La proporción de mutaciones a IPs en pacientes con fallo virológico disminuyó de 87% en 2006 a 17% en 2021 y para los INTR, disminuyó de 79% en 2006 a 45% en 2021. Conclusión: El nivel de resistencia a los ARVs ha disminuido de manera sustancial a lo largo de los últimos 16 años, probablemente por el uso de nuevos fármacos ARV con alta potencia que posibilitaron la intensificación de los tratamientos ARV y la implementación de criterios de fallo terapéutico más estrictos tanto a nivel clínico como virológico (AU)

Introduction: HIV resistance to antiretroviral (ARV) drugs is one of the main causes of therapeutic failure in children and adolescents living with the virus. Since 2006, the Cell Biology and Retrovirus Laboratory of the Garrahan Hospital has been performing the genotypic study of HIV-1 resistance to ARV drugs in order to identify mutations that reduce the susceptibility of the virus to the drugs that constitute ARV treatment. Objectives: The aim of this study was to assess the type and frequency of HIV resistance to ARV drugs through an analysis of 371 genotype studies performed between 2006 and 2021 in children and adolescents with HIV-1 acquired through motherto-child transmission and with medical request for genotype study due to therapeutic failure. Results: Between 2006 and 2013, the proportion of cases with resistance to at least one ARV drug class was greater than 90%, suggesting a direct association between virologic failure and decreased susceptibility of HIV-1 to one or more components of ART. From 2012 onwards, a progressive decrease in the level of HIV-1 resistance was observed, reaching 50% in 2021 (p<0.0001). The frequency of resistant mutations was different for each of the ARV classes, while resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs) did not change significantly over the study period, ranging from 27% to 75%. The proportion of drug-resistant mutations to protease inhibitors (PI) in patients with virologic failure decreased from 87% in 2006 to 17% in 2021 and for NNRTIs from 79% in 2006 to 45% in 2021. Conclusion: The level of resistance to ARV drugs has decreased substantially over the last 16 years, probably due to the use of new ARV drugs with high potency that allowed the intensification of ARV treatments and the implementation of stricter criteria for therapeutic failure both clinically and virologically (AU)

Registro argentino de COVID-19 en VIH (Estudio COVIDARE): características clínicas, epidemiológicas y factores asociados a hospitalización / Argentine Registry of COVID-19 in HIV (COVIDARE Study): clinical and epidemiological characteristics and factors associated with hospitalization

INTRODUCCIÓN: Existe controversia con respecto a los factores que determinan un mayor riesgo de gravedad y complicaciones por COVID-19 en personas que viven con VIH (PVVIH). Asimismo, hay datos limitados sobre el impacto de la vacunación contra SARS-CoV-2 en la hospitalización en esta población. OBJETIVOS: Describir las características clínicas y evolutivas de COVID-19 en PVVIH; Evaluar factores de riesgo para hospitalización; Evaluar el impacto de la vacunación en la hospitalización. Pacientes y MÉTODOS: Estudio observacional, prospectivo, multicéntrico (septiembre de 2020 a junio de 2022). Se registraron variables clínicas, inmunovirológicas, tratamiento antirretroviral (TARV), vacunación contra SARS-CoV-2 y hospitalización en PVVIH con COVID-19. Se realizaron análisis uni y multivariados examinando factores asociados a hospitalización utilizando dos modelos: primer modelo (sin vacunación) y segundo modelo (vacunación, mínimo una dosis). RESULTADOS: Se incluyeron 1.201 PVVIH. La mediana de edad fue 45 años. El 65,3% fueron hombres; el 38,7% presentó comorbilidades. Recibía TARV el 92,8% y presentó carga viral (CV) indetectable el 83,1%. La mediana de linfocitos T CD4+ fue de 600 céls/mm3. El 95,7% presentó síntomas. Las tasas de hospitalización, ingreso a UCI, requerimiento de oxígeno y muerte fueron 17,8%, 2,8%, 10,7% y 1,39%, respectivamente. De acuerdo con el análisis multivariado para el primer modelo, la edad > 60 años y las comorbilidades se asociaron a mayor riesgo de hospitalización, mientras que el sexo femenino y un recuento de linfocitos T CD4+ > 500 céls/mm3 tuvieron un efecto protector. En el segundo modelo sólo las comorbilidades se relacionaron con un mayor riesgo de hospitalización mientras que la vacunación y células CD4+ > 500 céls/mm3 la redujeron. CONCLUSIONES: En PVVIH las comorbilidades se asociaron con mayor tasa de hospitalización, mientras que tener linfocitos T CD4+ elevados y estar vacunado tuvieron un efecto protector. El TARV y la CV no tuvieron impacto en modelo alguno mientras que la edad y el sexo solo influyeron cuando no se consideró la vacunación.

BACKGROUND: There is controversy regarding the factors that determine a greater risk of severity and complications from COVID-19 in people living with HIV (PLHIV). Likewise, there are limited data on the impact of SARS-CoV-2 vaccination on hospitalization in this population. AIMS: To describe clinical characteristics and outcome of COVID-19 in PLHIV; To assess risk factors for hospitalization; To evaluate the impact of vaccination on hospitalization. METHODS: Multicenter, prospective, observational study (September 2020 to June 2022). Clinical and immunovirological variables, antiretroviral treatment (ART), SARS-CoV-2 vaccination, and hospitalization in PLHIV with COVID-19 were recorded. Univariate and multivariate analyzes were performed examining factors associated with hospitalization using two models: first model (without vaccination) and second model (vaccination, minimum one dose). RESULTS: 1,201 PLHIV were included. The median age was 45 years. 65.3% were men; 38.7% presented comorbidities. 92.8% received ART and 83.1% presented undetectable viral load (VL). The median CD4+ T-cell count was 600/mm3. 95.7% presented symptoms. The rates of hospitalization, ICU admission, oxygen requirement, and death were 17.8 %, 2.8%, 10.7% and 1.39%, respectively. According to the multivariate analysis for the first model, age > 60 years and comorbidities were associated with a higher risk of hospitalization, while female sex and CD4+ > 500/mm3 had a protective effect. In the second model, only the comorbidities were associated with a higher risk of hospitalization, while vaccination and CD4+ > 500/mm3 reduced it. CONCLUSIONS: in PLHIV, comorbidities were associated with a higher hospitalization rate, while having elevated CD4+ T-cell counts and being vaccinated had a protective effect. ART and VL had no impact in any model, while age and sex only had an influence when vaccination was not considered.

Reasons, safety and efficacy analysis for conversion of HAART to TAF/FTC/BIC among HIV-infected patients / 中华医学杂志(英文版)

BACKGROUND@#This study aimed to determine the reasons for conversion and elucidate the safety and efficacy of transition to tenofovir alafenamide/emtricitabine/bictegravir sodium (TAF/FTC/BIC) in highly active antiretroviral therapy (HAART)-experienced HIV-infected patients in real-world settings.@*METHODS@#We conducted a retrospective cohort study. The treatment conversion rationales, safety, and effectiveness in 1684 HIV-infected patients with previous HAART experience who switched to TAF/FTC/BIC were evaluated at Beijing Ditan Hospital from September 2021 to Auguest 2022.@*RESULTS@#Regimen simplification (990/1684, 58.79%) was the most common reason for switching, followed by osteoporosis or osteopenia (375/1684, 22.27%), liver dysfunction (231/1684, 13.72%), decline in tenofovir alafenamide/emtricitabine/elvitegravir/cobicistat (TAF/FTC/EVG/c) with food restriction (215/1684, 12.77%), virological failure (116/1684, 6.89%), and renal dysfunction (90/1684, 5.34%). In patients receiving non-nucleotide reverse transcriptase inhibitors (NNRTI)-containing regimens, lipid panel changes 1 year after switching indicated a difference of 3.27 ± 1.10 mmol/L vs . 3.40 ± 1.59 mmol/L in triglyceride ( P  = 0.014), 4.82 ± 0.74 mmol/L vs . 4.88 ± 0.72 mmol/L in total cholesterol ( P  = 0.038), 3.09 ± 0.70 mmol/L vs . 3.18 ± 0.66 mmol/L in low-density lipoprotein ( P  <0.001), and 0.99 ± 0.11 mmol/L vs . 0.95 ± 0.10 mmol/L in high-density lipoprotein ( P  <0.001). Conversely, among patients receiving booster-containing regimens, including TAF/FTC/EVG/c and lopinavir/ritonavir (LPV/r), lipid panel changes presented decreased trends. We also observed an improved trend in viral load suppression, and alanine transaminase (ALT), aspartate transaminase (AST), estimated glomerular filtration rate (eGFR), and serum creatinine levels after the transition ( P  <0.001).@*CONCLUSION@#The transition to TAF/FTC/BIC demonstrated good treatment potency. Furthermore, this study elucidates the motivations behind the adoption of TAF/FTC/BIC in real-world scenarios, providing clinical evidence supporting the stable conversion to TAF/FTC/BIC for HAART-experienced patients.

Efficacy and safety profiles of dolutegravir plus lamivudine vs . bictegravir/emtricitabine/tenofovir alafenamide in therapy-naïve adults with HIV-1 / 中华医学杂志(英文版)

BACKGROUND@#Dual regimen dolutegravir (DTG) plus lamivudine (3TC) has demonstrated non-inferior efficacy compared to DTG-based three-drug regimens (3DRs), yet directly comparative data regarding the efficacy and safety of DTG + 3TC and bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) for therapy-naïve people with human immunodeficiency virus (HIV)-1 (PWH) are still limited. We aimed to assess the antiviral potency and safety profiles of DTG + 3TC vs. B/F/TAF based on antiretroviral therapy (ART)-naïve PWH in China.@*METHODS@#This retrospective multicenter study enrolled PWH initiating ART with DTG + 3TC or B/F/TAF from 2020 to 2022 in Guangdong and Guangxi. We analyzed response rates based on target not detected (TND) status using intention-to-treat (ITT) analysis. Subgroups were formed based on baseline viral load (VL) (<100,000 vs . ≥100,000 copies/mL) and CD4 + cell count (<200 vs . ≥200 cell/µL). Median time to TND VL was assessed by Kaplan-Meier method. We also measured changes from baseline in CD4 + cell counts, CD4/CD8 ratio, lipid parameters, weight, creatinine (Cr), estimated glomerular filtration rate (eGFR), and drug-related adverse effects (DRAEs).@*RESULTS@#We enrolled 280 participants, including 137 (48.9%) on DTG + 3TC and 143 (51.1%) on B/F/TAF. At week 48, 96.4% (132/137) on DTG+3TC and 100% (143/143) on B/F/TAF achieved TND ( P = 0.064). At week 12, TND responses were higher with B/F/TAF (78.3% [112/143]) than DTG+3TC (30.7% [42/137]) ( P <0.001). This trend held across subgroups. B/F/TAF achieved TND faster (12 weeks) than DTG+3TC (24 weeks) ( P <0.001). No differences were seen in CD4 + cell count and CD4/CD8 ratio, except in the high-VL subgroup, where B/F/TAF showed better recovery. DRAEs were significantly lower with B/F/TAF (4.9% [7/143]) than with DTG + 3TC (13.1% [18/137]) ( P = 0.016). Lipid parameters, body weight, and Cr increased in both groups over 48 weeks, with DTG+3TC showing a more favorable effect on triglycerides, high-density lipoprotein (HDL) cholesterol, and weight gain.@*CONCLUSIONS@#In this real-life study, B/F/TAF led to a faster viral decline and fewer DRAEs compared to DTG+3TC. No significant difference was observed in the TND rate at week 48, regardless of baseline VL and CD4 + cell count. CD4 + recovery was superior for B/F/TAF in participants with high VL. The DTG + 3TC regimen had less impact on metabolic changes than B/F/TAF.

Incidence and factors associated with hepatitis B surface antigen seroclearance in patients co-infected with HBV/HIV during antiretroviral therapy in Guangdong, China / 中华医学杂志(英文版)

BACKGROUND@#Hepatitis B surface antigen (HBsAg) clearance is vital for a functional cure of hepatitis B virus (HBV) infection. However, the incidence and predictors of HBsAg seroclearance in patients co-infected with HBV and human immunodeficiency virus (HIV) remain largely unknown in Guangdong, China.@*METHODS@#Between 2009 and 2019, patients co-infected with HBV/HIV undergoing antiretroviral therapy (ART) in Guangzhou Eighth People's Hospital affiliated to Guangzhou Medical University were retrospectively reviewed with the endpoint on December 31, 2020. The incidence and risk factors for HBsAg seroclearance were evaluated using Kaplan-Meier and multivariate Cox regression analyses.@*RESULTS@#A total of 1550 HBV/HIV co-infected patients were included in the study, with the median age of 42 years and 86.0% (1333/1550) males. Further, 98.3% (1524/1550) received ART containing tenofovir disoproxil fumarate (TDF) plus lamivudine (3TC). HBV DNA was examined in 1283 cases at the last follow-up. Over the median 4.7 years of follow-up, 8.1% (126/1550) patients achieved HBsAg seroclearance, among whom 50.8% (64/126) obtained hepatitis B surface antibody, 28.1% (137/488) acquired hepatitis B e antigen seroconversion, and 95.9% (1231/1283) undetectable HBV DNA. Compared with patients who maintained HBsAg positive, cases achieving HBsAg seroclearance showed no differences in age, gender, CD4 + T cell count, alanine aminotransferase (ALT) level, or fibrosis status; however, they presented lower HBV DNA levels, lower HBsAg levels, and higher rates of HBV genotype B at the baseline. Multivariate analysis showed that baseline HBsAg <1500 cutoff index (COI) (adjusted hazard ratio [aHR], 2.74, 95% confidence interval [95% CI]: 1.48-5.09), ALT elevation >2 × upper limit of normal during the first six months after receiving ART (aHR, 2.96, 95% CI: 1.53-5.77), and HBV genotype B (aHR, 3.73, 95% CI: 1.46-9.59) were independent predictors for HBsAg seroclearance (all P <0.01).@*CONCLUSIONS@#Long-term TDF-containing ART has high anti-HBV efficacy including relatively high overall HBsAg seroclearance in HBV/HIV co-infected patients. Lower baseline HBsAg levels, HBV genotype B, and elevated ALT levels during the first six months of ART are potential predictors of HBsAg seroclearance.

Longitudinal analysis of immune reconstitution and metabolic changes in women living with HIV: A real-world observational study / 中华医学杂志(英文版)

BACKGROUND@#Women comprise more than half of people living with human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) worldwide and incomplete immune recovery and metabolic abnormalities affect them deeply. Studies of HIV antiretroviral therapy (ART) have a low female representation in China. We aimed to investigate immune reconstitution and metabolic changes of female HIV-positive cohort in China longitudinally.@*METHODS@#HIV-positive women who initiated ART from January 2005 to June 2021 and were followed up regularly at least once a year were included in this study. Immunological indicators (cluster of differentiation 4 [CD4] counts and CD8 counts), viral load (VL), and metabolic indicators were collected at follow-up. All data were collected from the China Disease Prevention and Control Information System (CDPCIS). VL was tested half a year, 1 year after receiving ART, and every other year subsequently according to local policy. CD4/CD8 ratio normalization was considered as the primary outcome and defined as a value ≥1. Incidence rate and probability of CD4/CD8 ratio normalization were estimated through per 100 person-years follow-up (PYFU) and Kaplan-Meier curve, respectively. Multivariate Cox regression was used to identify independent risk factors associated with CD4/CD8 ratio normalization. We further studied the rate of dyslipidemia, hyperuricemia, diabetes, liver injury, and renal injury after ART initiation with the chi-squared tests or Fisher's exact probability tests, and a generalized estimating equation model was used to analyze factors of dyslipidemia and hyperuricemia.@*RESULTS@#A total of 494 female patients with HIV/AIDS started ART within 16 years from January 2005 to June 2021, out of which 301 women were enrolled with a median duration of ART for 4.1 years (interquartile range, 2.3-7.0 years). The overall incidence rate of CD4/CD8 ratio normalization was 8.9 (95% confidence interval [CI], 7.4-10.6) per 100 PYFU, and probabilities of CD4/CD8 normalization after initiating ART at 1 year, 2 years, 5 years, and 10 years follow-up were 11.7%, 23.2%, 44.0%, and 59.0%, respectively. Independent risk factors associated with CD4/CD8 normalization were baseline CD4 cell counts <200 cells/μL, CD8 counts >1000 cells/μL, and more than 6 months from the start of combined ART (cART) to first virological suppression. Longitudinally, the rate of hypercholesterolemia (total cholesterol [TC]) and high triglyceride (TG) showed an increasing trend, while the rate of low high-density lipoprotein cholesterol (HDL) showed a decreasing trend. The rate of hyperuricemia presented a downtrend at follow-up. Although liver and renal injury and diabetes persisted during ART, the rate was not statistically significant. Older age and protease inhibitors were independent risk factors for increase of TC and TG, and ART duration was an independent factor for elevation of TC and recovery of HDL-C.@*CONCLUSIONS@#This study showed that women were more likely to normalize CD4/CD8 ratio in comparison with findings reported in the literature even though immune reconstruction was incomplete.

Metformin may be a viable adjunctive therapeutic option to potentially enhance immune reconstitution in HIV-positive immunological non-responders / 中华医学杂志(英文版)

Incomplete immune reconstitution remains a global challenge for human immunodeficiency virus (HIV) treatment in the present era of potent antiretroviral therapy (ART), especially for those individuals referred to as immunological non-responders (INRs), who exhibit dramatically low CD4 + T-cell counts despite the use of effective antiretroviral therapy, with long-term inhibition of viral replication. In this review, we provide a critical overview of the concept of ART-treated HIV-positive immunological non-response, and also explain the known mechanisms which could potentially account for the emergence of immunological non-response in some HIV-infected individuals treated with appropriate and effective ART. We found that immune cell exhaustion, combined with chronic inflammation and the HIV-associated dysbiosis syndrome, may represent strategic aspects of the immune response that may be fundamental to incomplete immune recovery. Interestingly, we noted from the literature that metformin exhibits properties and characteristics that may potentially be useful to specifically target immune cell exhaustion, chronic inflammation, and HIV-associated gut dysbiosis syndrome, mechanisms which are now recognized for their critically important complicity in HIV disease-related incomplete immune recovery. In light of evidence discussed in this review, it can be seen that metformin may be of particularly favorable use if utilized as adjunctive treatment in INRs to potentially enhance immune reconstitution. The approach described herein may represent a promising area of therapeutic intervention, aiding in significantly reducing the risk of HIV disease progression and mortality in a particularly vulnerable subgroup of HIV-positive individuals.

Genetic Subtypes and Pretreatment Drug Resistance in the Newly Reported Human Immunodeficiency Virus-Infected Men Aged≥50 Years Old in Guangxi / 中国医学科学院学报

Objective To analyze the genetic subtypes of human immunodeficiency virus (HIV) and the prevalence of pretreatment drug resistance in the newly reported HIV-infected men in Guangxi. Methods The stratified random sampling method was employed to select the newly reported HIV-infected men aged≥50 years old in 14 cities of Guangxi from January to June in 2020.The pol gene of HIV-1 was amplified by nested reverse transcription polymerase chain reaction and then sequenced.The mutation sites associated with drug resistance and the degree of drug resistance were then analyzed. Results A total of 615 HIV-infected men were included in the study.The genetic subtypes of CRF01_AE,CRF07_BC,and CRF08_BC accounted for 57.4% (353/615),17.1% (105/615),and 22.4% (138/615),respectively.The mutations associated with the resistance to nucleoside reverse transcriptase inhibitors (NRTI),non-nucleoside reverse transcriptase inhibitors (NNRTI),and protease inhibitors occurred in 8 (1.3%),18 (2.9%),and 0 patients,respectively.M184V (0.7%) and K103N (1.8%) were the mutations with the highest occurrence rates for the resistance to NRTIs and NNRTIs,respectively.Twenty-two (3.6%) patients were resistant to at least one type of inhibitors.Specifically,4 (0.7%),14 (2.3%),4 (0.7%),and 0 patients were resistant to NRTIs,NNRTIs,both NRTIs and NNRTIs,and protease inhibitors,respectively.The pretreatment resistance to NNRTIs had much higher frequency than that to NRTIs (2.9% vs.1.3%;χ2=3.929,P=0.047).The prevalence of pretreatment resistance to lamivudine,zidovudine,tenofovir,abacavir,rilpivirine,efavirenz,nevirapine,and lopinavir/ritonavir was 0.8%, 0.3%, 0.7%, 1.0%, 1.3%, 2.8%, 2.9%, and 0, respectively. Conclusions CRF01_AE,CRF07_BC,and CRF08_BC are the three major strains of HIV-infected men≥50 years old newly reported in Guangxi,2020,and the pretreatment drug resistance demonstrates low prevalence.

A comprehensive overview on the role of phytocompounds in human immunodeficiency virus treatment / 中西医结合学报

Acquired immune deficiency syndrome (AIDS) is a worldwide epidemic caused by human immunodeficiency virus (HIV) infection. Newer medicines for eliminating the viral reservoir and eradicating the virus are urgently needed. Attempts to locate relatively safe and non-toxic medications from natural resources are ongoing now. Natural-product-based antiviral candidates have been exploited to a limited extent. However, antiviral research is inadequate to counteract for the resistant patterns. Plant-derived bioactive compounds hold promise as powerful pharmacophore scaffolds, which have shown anti-HIV potential. This review focuses on a consideration of the virus, various possible HIV-controlling methods and the recent progress in alternative natural compounds with anti-HIV activity, with a particular emphasis on recent results from natural sources of anti-HIV agents. Please cite this article as: Mandhata CP, Sahoo CR, Padhy RN. A comprehensive overview on the role of phytocompounds in human immunodeficiency virus treatment. J Integr Med. 2023; 21(4):332-353.

Linfogranuloma venéreo genital en un hombre que tiene sexo con hombre: reporte de caso no importado en Chile / Lymphogranuloma venerous genital in men who have sex with men: a non-imported case report in Chile

Resumen El linfogranuloma venéreo (LGV) es una infección de transmisión sexual (ITS) causada por Chlamydia trachomatis. En los últimos años, ha emergido principalmente en hombres que tienen sexo con hombres (HSH). Es frecuente su asociación con otras ITS como el virus de inmunodeficiencia humana (VIH) y la sífilis. Si bien el compromiso genital es la forma de presentación clásica, el síndrome anorrectal constituye el principal cuadro clínico en la actualidad. Presentamos el caso de un HSH con infección por VIH en terapia anti-retroviral, herpes genital recurrente y sífilis latente tratada, sin viajes recientes al extranjero, con adenopatías inguinales fistulizadas a piel, asociada a una úlcera genital dolorosa, sin síntomas anorrectales ni sistémicos, refractario a múltiples tratamientos antibacterianos y antivirales. El estudio con RPC de secreción de la fístula fue positiva a C. trachomatis. Se trató con doxiciclina por seis semanas, con buena respuesta clínica, sin complicaciones.

Abstract Lymphogranuloma venereum (LGV) is a sexually transmitted infection caused by Chlamydia trachomatis bacteria. In the past years, it has emerged as a relevant infectious agent, mainly affecting men who have sex with men (MSM), frequently associated with other sexually transmitted infections as human immunodeficiency virus (HIV) and syphilis. Even though genital lesions correspond to the classical presentation of LGV, nowadays anorectal syndrome is more frequently reported. We present a MSM patient, HIV infected, being treated with antiretroviral drugs, with a history of recurrent genital herpes, also recently treated for a syphilis in a latent stage. He had no recent trips. He referred inguinal fistulized enlarged lymph nodes, associated with a painful genital ulcer, he denied anorectal or systemic symptoms. He had been treated with multiple antibiotic and antiviral drugs, with no clinical response. Molecular studies from the content of the fistulized lymph node identified C. trachomatis. The patient received doxycycline for 6 weeks, showing good clinical response.

La infección por vih en tiempos de pandemia: muchos retrocesos, innumerables desafíos / HIV infection in times of pandemic: many setbacks, countless challenges

Resumen Desde la llegada de la pandemia por COVID-19, se ha descrito un sinnúmero de consecuencias respecto a la infección por VIH en Chile, tanto en su diagnóstico como en su prevención, principalmente manifestadas en el descenso de la realización de exámenes serológicos, la interrupción de la atención, el retraso en el inicio de la terapia antirretroviral y la falta de acceso a métodos preventivos. A ello, se le suma el deterioro en algunas condiciones relacionadas con aspectos sociales y sobre salud mental. Todo esto implica, entre otras consecuencias, un probable empeoramiento en la situación epidemiológica de la infección por VIH en Chile. En el presente artículo, se revisarán algunos de los impactos señalados y se plantean algunos desafíos, para el enfrentamiento de esta problemática.

Abstract Since the arrival of the COVID-19 pandemic, countless consequences have been described regarding HIV infection in Chile, both in its diagnosis and prevention, mainly manifested in the decrease in serological tests, the interruption of care, the delay in starting antiretroviral therapy, and the lack of access to preventive methods. Added to this is the deterioration in some conditions related to social aspects and mental health. All this implies, among other consequences, a probable worsening in the epidemiological situation of HIV infection in Chile. Some of the designated impacts are reviewed in this article, and some challenges are raised to confront this problem.

Infección por SARS-CoV-2 en personas viviendo con VIH: tópicos del panorama mundial y en Chile / SARS-CoV-2 infection in people living with HIV: topics on the global panorama and in Chile

Resumen La enfermedad COVID-19 es una patología de origen infeccioso causada por el virus SARS-CoV-2 y fue declarada pandemia por la OMS el 11 de marzo 2020. A la fecha se registran más de 500 millones de personas infectadas y más de 6 millones de fallecidos en todo el mundo. Las personas que pertenecen a grupos de riesgo más vulnerables, particularmente aquellos que se encuentran en los extremos de la vida, con comorbilidades crónicas o inmunocomprometidas, son especialmente susceptibles a presentar un eventual mayor riesgo de infección, de gravedad y de mortalidad por esta enfermedad. Las personas que viven con VIH, especialmente aquellos en precarias condiciones inmunológicas o aquellas que aún no inician terapia antiretroviral, pueden ser un grupo especialmente susceptible de presentar complicaciones relacionadas a esta y otras enfermedades de origen infeccioso. Con esta revisión se pretende determinar la magnitud del impacto del virus SARS-CoV-2 en personas viviendo con VIH en Chile.

Abstract The COVID-19 disease is caused by the SARS-CoV-2 virus and was declared a pandemic by the WHO on March 11, 2020. To date, more than 500 million people have been infected and it has caused over 6 million deaths worldwide. People that belong to the most vulnerable risk groups, such as those at the extremes of life, patients with chronic comorbidities and those with severe immunosuppression, are especially susceptible to developing a severe form of COVID-19 infection and death. Subjects living with HIV, especially those in precarious immunological conditions or those in whom antiretroviral therapy is yet to be started, may be at risk of developing complications related to COVID-19, as observed with other infectious diseases. This review aims to determine the magnitude of the impact of the SARS-CoV-2 virus on people living with HIV in Chile.