Expresión de los componentes del inflamasoma y su relación con los marcadores de riesgo cardiovascular en personas con infección por HIV-1 / Expression of the inflammasome components and its relationship with cardiovascular risk markers in people living with HIV-1

Introducción. La infección por el HIV-1 induce un estado de inflamación crónico en el que participan los inflamasomas. El incremento de los parámetros inflamatorios es mayor en individuos con replicación viral activa que en aquellos con control de la replicación viral. Este proceso desencadena alteraciones metabólicas relacionadas con cambios en el perfil lipídico, lo cual podría incrementar el riesgo de eventos cardiovasculares, incluso en pacientes con terapia antirretroviral. Objetivo. Establecer si existe correlación entre la expresión de los componentes de los inflamasomas y los marcadores de riesgo cardiovascular en individuos con control de la replicación viral y en aquellos con replicación viral activa con terapia antirretroviral o sin ella. Materiales y métodos. Se estudiaron 13 individuos con control de la replicación viral y 40 con replicación viral activa (19 sin terapia antirretroviral y 31 con terapia). Se evaluaron los marcadores clásicos de riesgo cardiovascular y se cuantificó mediante RT-PCR la expresión de los componentes de los inflamasomas (NLRP1, NLRP3, NLRC4, AIM2, ASC, IL-1ß, IL-18 y caspasa-1), TLR2, TLR4, TGF-ß e IL-10. Resultados. Se observó que los pacientes con replicación viral activa y con terapia antirretroviral presentaron un incremento en la expresión de TLR2, TLR4 e IL-18, comparados con los controladores del HIV-1. Además, mostraron grandes valores de triglicéridos y lipoproteína de muy baja densidad (Very Low Density Lipopretein, VLDL), lo que se correlaciona positivamente con la expresión de los componentes de los inflamasomas NLRP1, NLRP3, NLRC4, AIM2, ASC y caspasa-1. Conclusión. El aumento en la expresión de los componentes de los inflamasomas en los individuos con replicación viral activa y con terapia antirretroviral se correlacionó con las concentraciones de triglicéridos y VLDL, lo que sugiere el papel de la activación inmunitaria y la terapia antirretroviral en el riesgo cardiovascular.

Introduction: HIV-1 infection induces a chronic inflammatory state in which inflammasomes participate. The increase in inflammatory parameters is higher in individuals with active viral replication (progressors) than in those with viral control (HIV-1 controllers). This process triggers metabolic alterations related to changes in the lipid profile, which could increase the risk of cardiovascular events, even in patients with antiretroviral therapy. Objective: To establish whether there was a correlation between the expression of inflammasome components and cardiovascular risk markers in HIV-1 controllers and progressors with or without antiretroviral therapy. Materials and methods: We studied 13 HIV-1 controllers and 40 progressors (19 without antiretroviral therapy and 31 with therapy) and evaluated in them classic markers of cardiovascular risk. Using RT-PCR we quantified the expression of inflammasome components (NLRP1, NLRP3, NLRC4, AIM2, ASC, IL-1ß, IL-18, and caspase-1), TLR2, TLR4, TGF-ß, and IL-10. Results: Progressors with antiretroviral therapy had an increased expression of TLR2, TLR4, and IL-18 compared to HIV-1 controllers. They also showed high levels of triglycerides and VLDL, which positively correlated with the expression of the inflammasome components NLRP1, NLRP3, NLRC4, AIM2, ASC, and caspase-1. Conclusion: Progressors receiving antiretroviral therapy exhibited an increased expression of the inflammasome components, which correlated with the levels of triglycerides and VLDL. This supports the role of inflammation in cardiovascular risk during HIV-1 infection.

Psychosocial Adjustment to Illness among HIV-Positive People from Buenos Aires, Argentina / Ajuste Psicosocial a la Enfermedad en personas HIV-positivas de la Ciudad de Buenos Aires, Argentina / Ajuste Psicossocial à doença nas pessoas HIV-positivas da Cidade de Buenos Aires, Argentina

Objective. To analyze the process of psychosocial adjustment to illness in a sample of people living with the Human Immunodeficiency Virus from Buenos Aires, Argentina. Methods. Cross-sectional analytical study. The sample consisted of 144 HIV-positive people chosen by simple random sampling. The PAIS-SR questionnaire was used to measure the Psychosocial Adjustment process, which is made up of 46 items organized into 7 domains, whose final score ranges between 0 and 100, interpreted so that the higher the score, the worse the psychosocial adjustment process. Results. The respondents reported were mostly male (82.63%), single (61.80%), with university studies (50.00%), without children (74.30%), and with a steady job (88.19%); the mean age of the participants was 43.8 years. The median global score was 51.4 (IQR: 12). The domains with the worst perception of psychosocial adjustment were: Health care orientation (Me: 56, IQR: 20), extended family relationship (Me: 55, IQR: 20), and Sexual relationship (Me: 54, IQR: 14), while those who had a better perception of adjustment were: Domestic environment (Me: 48, IQR: 8), Psychological distress (Me: 48, IQR: 17), Social environment (Me: 50, IQR: 18) and Vocational environment (Me: 50, IQR: 12). It was found that patients with a poor psychosocial adjustment process had low adherence to treatment, higher frequency of smoking, and sedentary lifestyle (p<0.001), while male sex, older age, and employment were related to a better psychosocial adjustment process (p<0.001). Conclusion. The process of psychosocial adjustment to illness in the study group is medium; adjustment was positively related to self-care habits such as better adherence to pharmacological treatment, physical activity, and not smoking.

Objetivo. Analizar el proceso de ajuste psicosocial en una muestra de personas que conviven con el Virus de la Inmunodeficiencia Humana de la Ciudad Autónoma de Buenos Aires, Argentina. Métodos. Estudio analítico de corte transversal. La muestra estuvo integrada por 144 personas HIV-positivas elegidos mediante muestreo aleatorio simple. Se empleó para la medición del proceso de Ajuste Psicosocial el cuestionario PAIS-SR, el cual está integrado por 46 ítems organizados en 7 dominios, cuyo puntaje final oscila entre 0 y 100, interpretándose de modo que, a mayor puntaje es peor el proceso de ajuste psicosocial. Resultados. Los encuestados fueron en su mayoría sexo masculino (82.63%), solteros (61.80%), con estudios universitarios (50%), sin hijos (74.30%) y con trabajo estable (88.19%); la media de edad de los participantes fue de 43.8 años. La mediana del puntaje global fue de 51.4 (RIQ:12). Los dominios con peor precepción de ajuste psicosocial fueron: Orientación al cuidado de la salud (Me: 56, RIQ: 20), Relación con la Familia Extendida (Me: 55, RIQ: 20) y Relaciones sexuales (Me: 54, RIQ: 14), mientras que los que tuvieron mejor percepción de ajuste fueron: Ambiente familiar (Me: 48, RIQ: 8), Distrés psicológico (Me: 48, RIQ: 17), Ambiente social (Me: 50, RIQ: 18) y Ambiente Laboral (Me: 50, RIQ: 12). Se encontró que los pacientes con un mal proceso de ajuste psicosocial presentaban una baja adherencia al tratamiento y más frecuencia de tabaquismo y sedentarismo (p<0.001), mientras que un mejor proceso de ajuste psicosocial se asoció a ser de sexo masculino, mayor edad y tener empleo estable (p<0.001). Conclusión. El proceso de ajuste psicosocial a la enfermedad en el grupo de estudio es medio; el ajuste se relacionó en forma positiva con hábitos de autocuidado como una mejor adherencia al tratamiento farmacológico, realización de actividad física y no fumar.

Objetivo. Analisar o processo de ajuste psicossocial numa amostra de pessoas que convivem com o Vírus da Imunodeficiência Humana da Cidade Autônoma de Buenos Aires, Argentina. Métodos. Estudo analítico de corte transversal. A amostra esteve integrada por 144 pessoas HIV-positivas elegidos mediante amostragem aleatório simples. Se empregou para a medição do processo de Ajuste Psicossocial o questionário PAIS-SR, o qual está integrado por 46 itens organizados em 7 domínios, cuja pontuação final oscila entre 0 e 100, interpretando-se de modo que, a maior pontuação é pior que o processo de ajuste psicossocial. Resultados. Os entrevistados foram na sua maioria do sexo masculino (82.63%), solteiros (61.80%), com estudos universitários (50%), sem filhos (74.30%) e com trabalho estável (88.19%); a média de idade dos participantes foi de 43 anos. A média da pontuação global foi de 51.4 (RIQ:12). Os domínios com pior percepção de ajuste psicossocial foram: Orientação ao cuidado da saúde (Me: 56, RIQ: 20), Relação com a Família Estendida (Me: 55, RIQ: 20) e Relações sexuais (Me: 54, RIQ: 14), enquanto que os que tiveram melhor percepção de ajuste foram: Ambiente familiar (Me: 48, RIQ: 8), Distresse psicológico (Me: 48, RIQ: 17), Ambiente social (Me: 50, RIQ: 18) e Ambiente Laboral (Me: 50, RIQ: 12). Se encontrou que os pacientes com um mal processo de ajuste psicossocial apresentavam uma baixa aderência ao tratamento e mais frequência de tabaquismo e sedentarismo (p<0.001), enquanto um melhor processo de ajuste social se associou a ser de sexo masculino, maior idade e posse de emprego se relacionaram com um melhor processo de ajuste psicossocial (p<0.001). Conclusão. O processo de ajuste psicossocial à doença no grupo de estudo é médio; o ajuste se relacionou em forma positiva com hábitos de autocuidado como uma melhor aderência ao tratamento farmacológico, realização de atividade física e não fumar.

Dynamic changes and influencing factors of HIV-1 DNA load in HIV-1 infected individuals under antiretroviral therapy / 中华流行病学杂志

Objective: To analyze the dynamic changes and influencing factors of HIV-1 DNA load in HIV-1 infected individuals under antiretroviral therapy (ART) in Dehong Dai and Jingpo autonomous prefecture, Yunnan province, and provide information support for the clinical use of HIV-1 DNA quantitative detection. Methods: The HIV infection cases in recent infection cohort from Dehong Center for Disease Control and Prevention during 2009-2018 were selected as study subjects. The dynamic curve of HIV-1 DNA load varrying with time was generated and logistic regression analysis was conducted to identify the risk factors for HIV-1 load in the recent follow up after ART and statistical analysis was performed by using SPSS 17.0. Results: Among the 113 HIV infection cases detected from the recent infection cohort, the recent HIV infection rate were 49.6%(56/113) males, sexual transmission cases and drug injection transmission cases accounted for 53.1% (60/113), 80.5% (91/113) and 19.5% (22/113), respectively. The dynamic changes curve showed that HIV-1 DNA load was relatively high (>800 copies /106 PBMCs) before ART, and droped rapidly (<400 copies /106 PBMCs) after ART for 1 year. However, HIV-1 DNA load decreased insignificantly from the second year of ART, and remained to be 269 copies/106 PBMCs after ART for 6 years. Univariable logistic regression analysis indicated that OR (95%CI) of CD8, CD4/CD8 and HIV-1 DNA load were 1.00 (1.00-1.00), 0.30 (0.09-1.05) and 1.01 (1.00-1.01), respectively. Multivariable logistic regression analysis showed that OR value of HIV-1 DNA load base was 1.00 (1.00-1.01). Conclusions: HIV-1 DNA load decreased significantly in the first year of ART, then remained stable for years. HIV-1 DNA load base was the key factor associated with the decrease of HIV-1 DNA load, the lower the HIV-1 DNA load base, the lower HIV-1 DNA load. Therefore, earlier ART can contribute to the decrease of HIV-1 DNA load.

Analysis of HIV-1 genetic subtype and pretreatment drug resistance among men who have sex with men infected with HIV-1 from 19 cities of 6 provinces in China / 中华流行病学杂志

Objective: To investigate the distribution of HIV-1 genetic subtypes and pretreatment drug resistance (PDR) among men who have sex with men (MSM) from 19 cities of 6 provinces in China. Methods: From April to November 2019, 574 plasma samples of ART-naive HIV-1 infected MSM were collected from 19 cities in Hebei, Shandong, Jiangsu, Zhejiang, Fujian, and Guangdong provinces, total ribonucleic acid (RNA) was extracted and amplified the HIV-1 pol gene region by nested polymerase chain reaction (PCR) after reverse transcription. Then sequences were used to construct a phylogenetic tree to determine genetic subtypes and submitted to the Stanford drug resistance database for drug resistance analysis. Results: A total of 479 samples were successfully amplified by PCR. The HIV-1 genetic subtypes included CRF01_AE, CRF07_BC, B, CRF55_01B, CRF59_01B, CRF65_cpx, CRF103_01B, CRF67_01B, CRF68_01B and unrecognized subtype, which accounted for 43.4%, 36.3%, 6.3%, 5.9%, 0.8%, 0.8%, 0.4%, 0.4%, 0.2% and 5.5%, respectively. The distribution of genetic subtypes among provinces is statistically different (χ2=44.141, P<0.001). The overall PDR rate was 4.6% (22/479), the drug resistance rate of non-nucleoside reverse transcriptase inhibitors, nucleoside reverse transcriptase inhibitors, and protease inhibitors were 3.5% (17/479), 0.8% (4/479) and 0.2% (1/479), respectively. The PDR rate of recent infections was significantly higher than that of long-term infections (χ2=4.634, P=0.031). Conclusions: The HIV-1 genetic subtypes among MSM infected with HIV-1 from 19 cities of 6 provinces in China are diverse, and the distribution of subtypes is different among provinces. The overall PDR rate is low, while the PDR rate of recent infections was significantly higher than that of long-term infections, suggesting the surveillance of PDR in recent infections should be strengthened.

Application of limiting antigen avidity enzyme immunoassay for estimating HIV-1 incidence in men who have sex with men / 中华流行病学杂志

Objective: To estimate the incidence of HIV-1 infection in men who have sex with men (MSM) in key areas of China through HIV-1 limiting antigen avidity enzyme immunoassay (LAg-Avidity EIA), analyze the deviation from the actual results and identify influencing factors, and provided reference for improving the accuracy of estimation results. Methods: Based on the principle of the cohort randomized study design, 20 cities were selected in China based on population size and the number of HIV-positive MSM. The sample size was estimated to be 700 according to the HIV-1 infection rate in MSM. MSM mobile phone app. was used to establish a detection appointment and questionnaire system, and the baseline cross-sectional survey was conducted from April to November 2019. LAg-Avidity EIA was used to identify the recent infected samples. The incidence of HIV-1 infection was calculated and then adjusted based on the estimation formula designed by WHO. The influencing factors were identified by analyzing the sample collection and detection processes. Results: Among the 10 650 blood samples from the participants, 799 were HIV-positive in initial screening, in which 198 samples (24.78%) missed during confirmation test. Only 621 samples were received by the laboratory. After excluding misreported samples, 520 samples were qualified for testing. A total of 155 samples were eventually determined as recent infection through LAg-Avidity EIA; Based on the estimation formula , the incidence of HIV-1 infection in MSM in 20 cities was 4.06% (95%CI:3.27%-4.85%), it increased to 5.53% (95%CI: 4.45%-6.60%)after the adjusting for sample missing rate. When the sample missing rate and misreporting rate were both adjusted, the incidence of HIV-1 infection in the MSM increased to 5.66% (95%CI:4.67%-6.65%). The actual incidence of HIV-1 infection in MSM in the 20 cities might be between 4.06% and 5.66%. Conclusions: Sample missing and misreporting might cause the deviation of the estimation of HIV-1 infection incidence. It is important to ensure the sample source and the quality of sample collection and detection to reduce the deviation in the estimation of HIV-1 infection incidence.

The affinity maturation, characteristics and application of HIV-1 broadly neutralizing antibodies / 中华预防医学杂志

Hundreds of broadly neutralizing antibodies(bNAbs) were successfully isolated from long-term nonprogression(LTNP) of human immunodeficiency virus type 1(HIV-1) infected individuals. Some bNAbs were illustrated could reduce the viral load and the risk of HIV-1 infection. Today, HIV-1 bNAbs are at the center of vaccine development and passive immunization treatment. Usually, the activity of neutralizing antibodies depends on the epitope. The affinity of neutralizing antibodies also plays a vital role in its inhibitory effect. Multiple affinity maturation in vivo actually provides the broad and potent neutralizing activity of HIV-1 bNAbs. When high affinity HIV-1 bNAbs applied in clinic, it can help immune system to remove virus with lower dosage and fewer side effect. While affinity maturation, HIV-1 bNAbs shows unique characteristics, such as extensive of somatic hypermutation(SHM), in-frame insertion and deletion and long CDR 3 region of heavy chain. The key points in the progress that HIV-1 bNAbs affinity maturation will help us understand the relationship between antibodies neutralizing capability and its characteristics.It also potentially provide a reference to design effective HIV-1 immunogen.

Impact of covid-19 on people living with HIV-1: care and prevention indicators at a local and nationwide level, Santo André, Brazil

ABSTRACT The world has been dealing with Aids for forty years, covid-19 accentuated societal inequalities and promoted a rupture in care and prevention, including for people living with HIV. We compiled official HIV indicators, analyzed the impact of covid-19 in Brazil, at São Paulo State (SP), and compared it to the municipality of Santo André (in the state of São Paulo), which adopted linkage/retention strategies to mitigate the impact of covid-19. From 2019 to 2020, suppression/adhesion rates remained stable. The number of new treatments decreased both in Brazil (-19.75%) and São Paulo (-16.44%), but not in Santo André, where 80% of new patients started treatment within 30 days from their first TCD4 test (70% in São Paulo and 64% in Brazil). However, PrEP dispensing increased during this period. The distribution of 2,820 HIV self-tests in Santo André lead to only one documented new HIV diagnosis linked to care. Synergistic strategies to swiftly diagnose and connect new cases, ensuring retention as well as rescuing missing patients deserve priority in the fight against HIV, especially in times of covid-19.

Selección del tratamiento de rescate en pacientes con VIH-1: respuesta y supervivencia / Selection method of rescue treatment in patients with HIV-1: response and survival

Resumen Objetivo: Determinar el impacto del uso de la prueba genotípica de resistencia en la respuesta y supervivencia a largo plazo de los pacientes infectados con el VIH-1 que presentaron fracaso a la terapia antirretroviral. Métodos: Se realizó un estudio de cohorte, retrospectivo, se definieron dos grupos basados en la forma de selección de la terapia de rescate utilizada: en base al resultado de la prueba genotípica de resistencia (grupo A) y en base al criterio de expertos (grupo B). Los pacientes fueron evaluados antes del cambio de la terapia de rescate según variables demográficas, clínicas y de laboratorio y evaluados a los 6, 12, 18, y 24 meses del cambio de tratamiento según respuesta virológica, respuesta de células CD4+, incidencia de enfermedades oportunistas y supervivencia. La información fue obtenida de las actas de la Comisión Nacional de Terapia Antirretroviral, la base de datos del IPK y las Historias Clínicas. Se utilizaron números absolutos y porcentajes, media y mediana, con sus respectivas desviaciones estándares (DE), Chi2, se aplicó el Riesgo Relativo (RR), prueba U de Mann-Whitney, y el método de Kaplan-Meier. Resultados: Los pacientes de grupo A tuvieron 1,44 veces mayor probabilidad de alcanzar supresión virológica completa que los pacientes del grupo B a los 6 meses, RR 1,44 (1,046- 2,054) p=0,017. El incremento promedio de Linfocitos T CD4+ fue de 117,40 células/mm3 en pacientes del grupo A y de 30,04 células/mm3 en pacientes del grupo B, p<0,005 a los 12 meses de iniciado el tratamiento. La incidencia de enfermedades oportunistas fue de 25,7% en el grupo B y de 5,6% en grupo A. El mayor porcentaje de sobrevida acumulada se observó en el grupo el grupo A (98,1%), en comparación con el grupo B (79%). Conclusiones: Los pacientes en los cuales el tratamiento de rescate se escogió basado en una prueba genotípica de resistencia tuvieron una mejor respuesta virológica, un mayor incremento de Linfocitos T CD4+ y una mayor supervivencia que aquellos en los que el tratamiento se eligió basado en el criterio de expertos.

Abstract Objective: To determine the impact of the use of genotypic resistance testing on the response and long-term survival of HIV-1 infected patients who have failed antiretroviral therapy. Methods: A retrospective cohort study was carried out; two groups were defined based on the method of selection of the rescue therapy used: based on the result of the genotypic resistance test (group A) and based on the criteria of experts (group B). The patients were evaluated before the change of rescue therapy according to demographic, clinical and laboratory variables and evaluated at 6, 12, 18, and 24 months after the change of treatment according to virological response, CD4 + cell response, incidence of opportunistic diseases. and survival. The information was obtained from the minutes of the National Commission for Antiretroviral Therapy, the IPK database and the Medical Records. Absolute numbers and percentages, mean and median, with their respective standard deviations (SD), Chi2, were used, the Relative Risk (RR), the Mann-Whitney U test, and the Kaplan-Meier method were applied. Results: Group A patients were 1.44 times more likely to achieve complete virological suppression than group B patients at 6 months, RR 1.44 (1.046-2.054) p = 0.017. The average increase in CD4 + T lymphocytes was 117.40 cells / mm3 in group A patients and 30.04 cells / mm3 in group B patients, p <0.005 12 months after startin treatment. The incidence of opportunistic diseases was 25.7% in group B and 5.6% in group A. The highest percentage of cumulative survival was observed in group A (98.1%), compared to the group B (79%). Conclusions: Patients in whom salvage treatment was chosen based on a genotypic resistance test had a better virological response, a greater increase in CD4 + T lymphocytes, and a longer survival than those in whom treatment was chosen based on expert judgment.

Human immunodeficiency virus infection and syphilis among homeless people in a large city of Central-Western Brazil: prevalence, risk factors, human immunodeficiency virus-1 genetic diversity, and drug resistance mutations

ABSTRACT Homeless people are at high risk for sexually transmitted infections (STIs), such as human immunodeficiency virus (HIV) infection and syphilis. We investigated the epidemiology of HIV-1 infection and syphilis among homeless individuals in a large city in Central-Western Brazil. In this cross-sectional study, we interviewed and tested 355 individuals from September 2014 to August 2015. Rapid test samples positive for syphilis were retested using the Venereal Disease Research Laboratory (VDRL) test. Blood samples from HIV-infected participants were collected for POL sequencing using HIV-1 RNA extracted from plasma, reverse transcription, and nested polymerase chain reaction. Anti-HIV-1-positive samples were subtyped by sequencing the nucleotides of HIV-1 protease and part of the HIV-1 reverse transcriptase genes. Transmitted and acquired drug resistance mutations and susceptibility to antiretroviral drugs were also analyzed. Anti-HIV was positive in 14 patients (3.9%; 95% confidence interval [CI]: 2.3-6.4). HIV-1 RNA was detected in 8 of the 14 samples. Two of the eight (25%) isolates showed HIV-1 drug resistance mutations. Furthermore, 78 (22%; 95% CI: 17.9-26.5) and 29 (8.2%; 95% CI: 5.6-11.4) homeless individuals tested positive for syphilis using the rapid test and VDRL test, respectively. Two individuals were anti-HIV-1 and VDRL test positive. Daily alcohol use (adjusted odds ratio [AOR]: 3.2, 95% CI: 1.0-10.4), sex with people living with HIV (PLWH) infection (AOR: 6.8, 95% CI: 1.9-25.0), and sex with people of the same sex (AOR: 5.4, 95% CI: 1.7-17.5) were predictors of HIV infection. Age ≤35 years (AOR: 3.8, 95% CI: 1.4-10.8), previous syphilis testing (AOR: 3.5, 95% CI: 1.4-8.4), history of genital lesions (AOR: 4.9, 95% CI: 1.3-19.1), and crack use in the last six months (AOR: 3.1, 95% CI: 1.3-7.6) were predictors of syphilis. Our findings highlight the importance of STI prevention and control strategies among the homeless.

Selective elimination of host cells harboring replication-competent human immunodeficiency virus reservoirs: a promising therapeutic strategy for HIV cure / 中华医学杂志(英文版)

Many seminal advances have been made in human immunodeficiency virus (HIV)/AIDS research over the past four decades. Treatment strategies, such as gene therapy and immunotherapy, are yielding promising results to effectively control HIV infection. Despite this, a cure for HIV/AIDS is not envisioned in the near future. A recently published academic study has raised awareness regarding a promising alternative therapeutic option for HIV/AIDS, referred to as "selective elimination of host cells capable of producing HIV" (SECH). Similar to the "shock and kill strategy," the SECH approach requires the simultaneous administration of drugs targeting key mechanisms in specific cells to efficiently eliminate HIV replication-competent cellular reservoirs. Herein, we comprehensively review the specific mechanisms targeted by the SECH strategy. Briefly, the suggested cocktail of drugs should contain (i) latency reversal agents to promote the latency reversal process in replication-competent reservoir cells, (ii) pro-apoptotic and anti-autophagy drugs to induce death of infected cells through various pathways, and finally (iii) drugs that eliminate new cycles of infection by prevention of HIV attachment to host cells, and by HIV integrase inhibitor drugs. Finally, we discuss three major challenges that are likely to restrict the application of the SECH strategy in HIV/AIDS patients.

The influence of HLA/HIV genetics on the occurrence of elite controllers and a need for therapeutics geotargeting view

The interaction of HIV-1, human leukocyte antigen (HLA), and elite controllers (EC) compose a still intricate triad. Elite controllers maintain a very low viral load and a normal CD4 count, even without antiretrovirals. There is a lot of diversity in HIV subtypes and HLA alleles. The most common subtype in each country varies depending on its localization and epidemiological history. As we know EC appears to maintain an effective CD8 response against HIV. In this phenomenon, some alleles of HLAs are associated with a slow progression of HIV infection, others with a rapid progression. This relationship also depends on the virus subtype. Epitopes of Gag protein-restricted by HLA-B*57 generated a considerable immune response in EC. However, some mutations allow HIV to escape the CD8 response, while others do not. HLA protective alleles, like HLA-B*27, HLA-B*57 and HLA-B*58:01, that are common in Caucasians infected with HIV-1 Clade B, do not show the same protection in sub-Saharan Africans infected by HIV-1 Clade C. Endogenous pathway of antigen processing and presentation is used to present intracellular synthesized cellular peptides as well as viral protein fragments via the MHC class I molecule to the cytotoxic T-lymphocytes (CTLs). Some epitopes are immunodominant, which means that they drive the immune reaction to some virus. Mutation on an anchor residue of epitope necessary for binding on MHC class I is used by HIV to escape the immune system. Mutations inside or flanking an epitope may lead to T cell lack of recognition and CTL escape. Studying how immunodominance at epitopes drives the EC in a geographically dependent way with genetics and immunological elements orchestrating it may help future research on vaccines or immunotherapy for HIV. 2021 Sociedade Brasileira de Infectologia. Published by Elsevier España, S.L.U. This is an open access article under the CC BY-NC-ND license

Evaluation of Differences in Metabolic and Immunologic Markers and Cardiovascular Risk in HIV-1 Patients / Evaluación de la relación entre marcadores metabólicos, inmunológicos y de riesgo cardiovascular en pacientes con VIH-1 / Avaliação da relação entre marcadores metabólicos, imunológicos e de risco cardiovascular em pacientes com HIV-1

Introduction:hiv infection induces an exacerbated chronic inflammatory response, which triggers met-abolic disorders and cardiovascular diseases; however, there are individuals, known as hiv controllers, who do not have typical progression markers. As cardiovascular risk tests are not accurate on hiv-1 infected patients, the study of metabolic and inflammatory parameters in individuals with different patterns of progression could contribute to the definition of predictors of cardiovascular disease in this population. The aim of this study was to compare hiv controllers and hiv progressors (with and without antiretroviral therapy) as well as with healthy controls in order to explore differences and correlations in metabolic and inflammatory biomarkers associated with cardiovascular risk. Materials and methods:This was a cross-sectional analytical study which included 63 individuals infected with hiv-1 classified as hiv controllers or progressors (with or without antiretroviral therapy), and a healthy control group. The following parameters were determined: carotid intima-media thickness (cimt); cardiovascular risk scores; lipid profile, fasting glucose, high-sensitivity crp, D-dimer, sCD14, sCD163, il-6, and il-18. Data were compared with Anova or Kruskal­Wallis, and correlations were evaluated by the Spearman coef-ficient. Results: While there were no significant differences in Framingham, dad or cimt values, hiv con-trollers exhibited lower triglycerides levels when compared with hiv progressors. No differences were observed in markers, such as high-sensitivity crp, il-6, il-18, and sCD163, among the groups. The median hdl value was higher in hiv progressors on antiretroviral therapy, and cimt in hiv controllers was nega-tively correlated with sCD14. Conclusion:hiv controllers have a different cardiovascular profile than hivprogressors according to their values in metabolic and immunological biomarkers

Introducción: la infección por vih-1 induce una respuesta inflamatoria crónica exacerbada que desencadena alteraciones metabólicas y cardiovasculares; sin embargo, algunos individuos "controladores" no presentan los marcadores de progresión típicos. Dado que las pruebas que evaluan el riesgo cardiovascular carecen de precisión en pacientes con vih-1, el estudio de parámetros inflamatorios en individuos con diferente progresión podría aportar a la definición de predictores de enfermedad cardiovascular en esta población. El objetivo es explorar diferencias y correlaciones en biomarcadores metabólicos e inflamatorios asociados con riesgo cardiovascular, comparando individuos controladores y progresores con y sin terapia antiviral. Materiales y métodos: estudio analítico transversal con 63 individuos infectados por vih-1, clasificados en controladores y progresores (con terapia antiviral y sin esta), y controles sanos. Se midió el grosor de la íntima media carotidea (cimt), puntajes de riesgo cardiovascular y cuantificación de perfil lipídico, glucemia en ayunas, pcr ultrasensible, dímero D, sCD14, sCD163, il-6 e il-18. Se realizó comparación por Anova o Kruskal-Wallis y correlación por coeficiente de Spearman. Resultados: no hubo diferencias significativas en índices de Framingham, dad o cimt, pero los individuos controladores presen-taron menores valores de triglicéridos, comparados con los progresores. No se observaron diferencias en pcr ultrasensible, il-6, il-18, y sCD163, entre los grupos estudiados. La mediana del hdl fue mayor en los progresores con terapia antiviral y el cimt en los controladores se correlacionó negativamente con sCD14. Conclusión: los individuos controladores presentan un perfil cardiovascular diferente a los individuos progresores, de acuerdo con los biomarcadores metabólicos e inmunológicos evaluados

Introdução: a infecção pelo hiv-1 induz resposta inflamatória crônica exacerbada, que desencadeia alte-rações metabólicas e doenças cardiovasculares; no entanto, existem indivíduos, chamados controlado-res, que não possuem os marcadores de progressão típicos. Tendo em vista que os testes que avaliam o risco cardiovascular carecem de precisão em pacientes com hiv-1, o estudo de parâmetros metabólicos e inflamatórios em indivíduos com diferentes padrões de progressão pode contribuir para a definição de preditores de doença cardiovascular nessa população. O objetivo é explorar diferenças e correlações em biomarcadores metabólicos e inflamatórios associados ao risco cardiovascular, comparando indiví-duos controladores e progressores submetidos ou não à terapia antiviral. Materiais e métodos: Estudo analítico transversal que incluiu 63 indivíduos infectados pelo hiv-1, classificados como controladores e progressores (com e sem terapia antiviral), além de grupos controle saudáveis. Realizou-se a medição da espessura da íntima média da carótida (cimt), pontuações de risco cardiovascular; e quantificação do perfil lipídico, glicemia em jejum, pcr ultrassensível, dímero d, sCD14, sCD163, il-6 e il-18. A comparação foi feita por Anova ou teste de Kruskal-Wallis e a correlação pelo coeficiente de Spearman. Resultados.Embora não tenha havido diferenças significativas nos índices de Framingham, dad ou cimt, os indivíduos controladores apresentaram valores de triglicerídeos mais baixos, em comparação com os progressores. Não foram observadas diferenças em marcadores como pcr ultrassensível, il-6, il-18 e sCD163, entre os grupos estudados. O hdl médio foi maior em indivíduos progressores em terapia antiviral, e o cimtem indivíduos controladores foi negativamente correlacionado com o sCD14. Conclusão: os indivíduos controladores apresentam um perfil cardiovascular diferente dos indivíduos progressores, de acordo com os biomarcadores metabólicos e imunológicos avaliados

HIV-1 genetic diversity and drug resistance mutations in the northern Brazilian region

ABSTRACT Brazil is a huge continental country with striking geographic differences which are well illustrated in the HIV/AIDS epidemic. Contrasting with the significant decline in the national AIDS detection rate in the last decade, a linear growth has been reported in the Northern region. Despite its public health and epidemiologic importance, there is scarce HIV-1 molecular data from Northern Brazil. This scoping review summarizes recent epidemiologic data with special emphasis on HIV-1 genetic diversity and antiretroviral drug resistance mutations in patients from the seven Northern states of Brazil. Studies from the Northern Brazil on different HIV-1 genomic regions, mostly pol (protease/reverse transcriptase) sequences of naïve/antiretroviral treated adults/children were retrieved from PubMed/MEDLINE electronic database. These studies indicate a consistent molecular profile largely dominated by HIV-1 subtype B with minor contribution of subtypes F1 and C and infrequent detection of other subtypes (A1, D, K), recombinants (BF1, BC), circulating recombinant forms (CRF) as the new CRF90_BF1 and CRF02_AG-like, CRF28-29_BF-like, CRF31_BC-like, and a potential new CRF_BF1. This pattern indicates a founder effect of subtype B and the introduction of non-B-subtypes and recombinants probably generated in the Southern/Southeastern regions. In naïve populations transmitted drug resistance (TDR) can impact the outcome of first-line antiretroviral treatment and prophylactic/preventive regimens. In the Northern region TDR rates are moderate while patients failing highly active antiretroviral therapy (HAART) showed high prevalence of acquired drug resistance mutations. The limited HIV-1 molecular data from Northern Brazil reflects the great challenges to generate comprehensive scientific data in isolated, underprivileged areas. It also highlights the need to invest in local capacity building which supported by adequate infrastructure and funding can promote robust research activities to help reduce the scientific asymmetries in the Northern region. Currently the impacts of the overwhelming COVID-19 pandemic on the expanding HIV/AIDS epidemic in Northern Brazil deserves to be closely monitored.

Time-dependent decay of detectable antibodies against SARS-CoV-2: A comparison of ELISA with two batches of a lateral-flow test

ABSTRACT Background: Large-scale epidemiological studies of seroprevalence of antibodies against SARS-CoV-2 often rely on point-of-care tests that provide immediate results to participants. Yet, little is known on how long rapid tests remain positive after the COVID-19 episode, or how much variability exists across different brands and even among batches of the same test. Methods: In November 2020, we assessed the sensitivity of three tests applied to 133 individuals with a previous positive PCR result between April and October. All subjects provided finger prick blood samples for two batches (A and B) of the Wondfo lateral-flow IgG/IgM test, and dried blood spot samples for the S-UFRJ ELISA test. Results: Overall sensitivity levels were 92.5% (95% CI 86.6-96.3), 63.2% (95% CI 54.4-71.4) and 33.8% (95% CI 25.9-42.5) for the S-UFRJ test, Wondfo A and Wondfo B tests, respectively. There was no evidence of a decline in the positivity of S-UFRJ with time since the diagnosis, but the two Wondfo batches showed sharp reductions to as low as 41.9% and 19.4%, respectively, for subjects with a positive PCR in June or earlier. Positive results for batch B of the rapid test were 35% to 54% lower than for batch A at any given month of diagnosis. Interpretation: Whereas the ELISA test showed high sensitivity and stability of results over the five months of the study, both batches of the rapid test showed substantial declines, with one of the batches consistently showing lower sensitivity levels than the other. ELISA tests based on dried-blood spots are an inexpensive alternative to rapid lateral-flow tests in large-scale epidemiological studies.

Serosurvey of anti-treponema pallidum (syphilis), antihepatitis C virus and anti-HIV antibodies in homeless persons of São Paulo city, southeastern Brazil

ABSTRACT Homeless persons have been considered as one of the most susceptible populations to sexually transmitted infections. In Brazil, these population experienced an increase of 140% from 2012 to 2020. Accordingly, the present study aimed to assess the seroprevalence of anti-Treponema pallidum, anti-HCV, anti-HIV antibodies, and the risk factors associated with homeless persons in a daytime attendance shelter of São Paulo city during the syphilis epidemic in Brazil. Blood samples of 116 volunteers and epidemiological data were conveniently collected in the shelter from June through August 2018. Detection of syphilis, HCV, and HIV antibodies was performed by chemiluminescent microparticle immunoassay (CMIA). CMIA-reagent samples for anti-T. pallidum antibodies were confirmed by Venereal Disease Research Laboratory (VDRL) non-treponemal test. VDRL non-reagent samples were confirmed by treponemal rapid immunochromatographic test. A rapid immunoblot assay confirmed seropositivity to HIV. Overall, anti-T. pallidum antibodies were observed in 29/116 (25.0%), anti-HCV antibodies in 4/116 (3.4%), and anti-HIV antibodies in 2/116 (1.7%) individuals, both co-infected with anti-T. pallidum antibodies. Associated risk factors for syphilis in homeless persons were being born or previously living in another city (p = 0.043) and becoming homeless due to family conflicts (p = 0.035). Besides homeless vulnerability, worldwide shortage of benzathine penicillin supply and increasing of syphilis testing access through rapid testing in primary health care services may have also impacted disease spreading at the time. The prevalence of syphilis found herein is the highest worldwide to date in this population.

The Recent HIV-1 Infections in Blood Donors of Fuzhou Zone / 中国实验血液学杂志

OBJECTIVE@#To investigate the recent HIV-1 infections of the blood donors in Fuzhou zone.@*METHODS@#The positive HIV antibody confirmatory samples in Fuzhou zone from 2012 to 2016 were collected and tested by LAg-Avidity EIA, and HIV long-term infections or recent infections were determined.@*RESULTS@#405 371 cases of blood donors were tested in the period from 2012 to 2016, and 94 HIV confirmatory positive samples were collected. 35 cases were recent infections determined by LAg-Avidity EIA, the annual HIV-1 incidences were 1.326‰, 0.845‰, 0.694‰, 1.148‰ and 0.364‰, the average incidences were 0.863‰. Among 94 cases of HIV confirmatory positive donors，58 cases were first donors and 36 cases were repeated donors, 17(29.3%) and 18 (50.0%) cases were recent infections respectively, which showed statistical significance（χ@*CONCLUSION@#The HIV-1 incidences were stable among blood donors in Fuzhou zone. The percentage of HIV-1 recent infections in repeated donors were more higher than that in first donors.

Exploration of an Efficient Simultaneous Molecular Detection Method of HIV, HCV, and Syphilis from a Single Dried Blood Spot / 生物医学与环境科学（英文）

Objective@#The aim of the present study was to evaluate the performance of the simultaneous detection of HIV-1 RNA, HIV-1 DNA, and HCV RNA using one dried blood spot (DBS) as an alternative sample to plasma.@*Method@#A total of 571 paired DBS/plasma samples were collected from men who have sex with men (MSM) and injection drug users (IDUs), and serological and molecular assays were performed. Using plasma results as the reference standard, the performance of DBS tests for HIV-1 RNA, HIV-1 DNA, and HCV RNA was evaluated. Pearson's correlation coefficients and Bland-Altman analysis were performed to assess the correlation and concordance between DBS and plasma.@*Results@#Among paired plasma/DBS samples with detectable HIV-1 RNA and HCV RNA, five samples (5/32) were not detectable in DBS, while measurable HIV-1 RNA levels were present in plasma (1.44 to 3.99 log @*Conclusion@#The performance of the simultaneous detection of HIV-1 RNA, HIV-1 DNA, and HCV RNA using one DBS was acceptable. DBS, as an alternative sample to plasma, may be a viable option for the simultaneous detection of HIV-1 RNA, HIV-1 DNA, and HCV RNA in resource-limited settings or for individuals living in areas that are difficult to access.

Prevalencia de resistencia transmitida a drogas antirretrovirales en pacientes con infección por VIH en Chile (2014-2018)

Background: Transmitted drug resistance (TDR) occurs in patients with HIV infection who are not exposed to antiretroviral drugs but who are infected with a virus with mutations associated with resistance. Aim: To determine the prevalence of TDR and characterize HIV reverse transcriptase and protease mutation patterns. Material and Methods: HIV infected antiretroviral treatment-naive patients treated in three centers between 2014 and 2018 were studied. A genotyping study was carried out. The HIVdb Program (Stanford University) and the World Health Organization (WHO) TDR surveillance mutation list were used to register resistance-associated mutations. Results: We enrolled 220 patients aged a median of 29 (interquartile range (IQR) 24-34) years, 99% men. Median CD4 count was 365 cells/μL (IQR 250-499 cells/μL) and median viral load was 39.150 copies/mL (IQR 9,270 −120,000). The overall prevalence of RTD was 10.45% (95% CI 6.7-15.2, N = 23/220). The higher frequency of TDR was against non-nucleoside reverse transcriptase inhibitors, reaching 9.0% (95% CI 5.6-13.6), followed by nucleoside reverse transcriptase inhibitors reaching 1.8% (95% CI 0.49-4.5) and protease inhibitors reaching 0.45% (95% CI 0.01-2.5). The mutations in reverse transcriptase were M41L, L210W, D67N, K70E, M184V, K103N (6.36%, 95% CI 3.5-10.4), G190A, E138A, K101E, and I84V in protease. Conclusions: These results should prompt a change in recommendations for starting antiretoviral therapy, especially in first-line regimens that include non-nucleoside reverse transcriptase inhibitors.

Impacto de la viremia de bajo grado en el riesgo de fallo virológico en pacientes con infección por VIH-1 / Impact of low-grade viremia on the risk of virological failure in patients with HIV-1 infection on antiretroviral therapy

Resumen Introducción: Cargas virales (CV) entre 20-200 copias/mL se consideran cargas virales de bajo grado (CVBG). Su implicancia clínica y manejo no han sido definidos. Objetivo: Evaluar el impacto de CVBG en el riesgo de desarrollo posterior de fallo virológico (FV). Pacientes y Métodos: Se incluyeron pacientes ≥ 18 años, desde enero de 2009 a diciembre de 2019, con infección por VIH-1 con CV< 20 copias/mL, por un mínimo de seis meses y/o en dos muestras consecutivas bajo tratamiento anti-retroviral . Se realizó seguimiento de las CV estrati ficándolas: CV < 20 copias/mL, CVBG (20-50 copias/mL y 51-200 copias/mL) y FV. Mediana de seguimiento 25 meses (IQR 15-31). Resultados: Fueron incluidos 1.416 pacientes con CV < 20 copias/ mL bajo TARV. De ellos, 797 permanecieron con CV< 20 copias/mL durante el seguimiento, 144 presentaron CV entre 20-50 copias/mL, 384 entre 51-200 copias/mL y 91 presentaron FV sin CVBG previa. De los 528 pacientes que tuvieron CVBG, 110 (20,1%) fallaron, riesgo 3,45 veces superior respecto a los que no tuvieron CVBG previa. El riesgo de FV fue 3,27 mayor para aquellos que tuvieron CVBG entre 51-200 copias/mL vs 20-50 copias/mL. Discusión: El estudio permite relacionar la CVBG con el FV posterior, siendo el mayor riesgo CVBG entre 51-200 copias/mL.

Abstract Background: Viral loads (VL) between 20-200 copies/mL are considered low-grade viral loads (LGVL). Its clinical implications and management have not been defined. Aim: To evaluate the impact of LGVL on the risk of subsequent development of virological failure (VF). Methods: Patients ≥ 18 years, with HIV-1 infection who had VL < 20 copies/mL for at least six months and/or in two consecutive samples under antiretroviral therapy (ART) were included, between January 1st, 2009 and December 31, 2019. Follow-up of the VLs was carried out stratifying them in VL < 20 copies/mL, LGVL (20-50 copies/mL and 51-200 copies/mL) and VF. Median follow-up 25 months (IQR 15-31). Results: 1,416 patients were included who reached VL < 20 copies/ml under ART, 797 patients remained with CV < 20 copies/mL during follow-up, 144 patients had VL between 21-50 copies/mL, 384 between 51-200 copies/mL and 91 had VF without previous LGVL. Out of 528 patients who had LGVL, 110 failed, risk 3.45 times higher than those who had no previous LGVL. Risk 3.27 times higher of VF for those who had LGVL between 51-200 copies/mL compared to 20-50 copies/mL. Discussion: The study allows to relate the LGVL with VF. This association was observed more frequently with LGVL between 51-200 copies/mL