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ABSTRACT Despite being subject to lower AIDS-related mortality rates and having a higher life expectancy, patients with HIV are more prone to develop non-AIDS events. A low CD4+/CD8+ ratio during antiretroviral therapy identifies people with heightened immune senescence and increased risk of mortality. In clinical practice, finding determinants of a low CD4+/CD8+ ratio may be useful for identifying patients who require close monitoring due to an increased risk of comorbidities and death. We performed a prospective study on the evolution of the CD4+/CD8+ ratio in 60 patients infected with HIV (80% males), who were subjected to two different antiretroviral regimens: early and deferred therapy. The initial CD4+/CD8+ ratio was ≤1 for 70% of the patients in both groups. Older age, CD4+ cell count at inclusion, Nadir CD8+T-cell count, and Initial CD4+/CD8+ ratio ≤ 1 were risk factors for lack of ratio recovery. In the multivariate analysis, a CD4+/CD8+ ratio > 1 at the start of the treatment was found to be a determinant factor in maintaining a CD4+/CD8+ ratio > 1. The nadir CD4+T-cell count was lower in the deferred therapy group (p=0.004), and the last CD4+/CD8+ ratio ≤1 was not associated with comorbidities. Ratio recovery was not associated with the duration of HIV infection, time without therapy, or absence of AIDS incidence. A greater improvement was observed in patients treated early (p=0.003). In contrast, the slope of increase was slower in patients who deferred treatment. In conclusion, the increase in the CD4+/CD8+ ratio occurred mostly for patients undergoing early strategy treatment and its extension did not seem to be related to previous HIV-related factors.
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Centenarians are the best example of successful aging in humans. This work aimed to understand if immune status is associated with survival in Cuban centenarians. In a previous study, our group enrolled 43 centenarians and evaluated their immune status and functional capacity. 41 out of 43 recruited centenarians received follow-up phone calls, during a period of 2 years. Absolute CD4 + T cell count was higher among survivors, while the frequency of CD8 + CCR7-CD45RA + , CD8 + CD45RA + CD28-, and CD4 + CD28- T cells was higher among non-survivors. We also found that higher frequencies of terminally differentiated T cells were related to a higher risk of death, while centenarians with higher frequencies of T cells were more likely to survive. Surprisingly, neither serum inflammatory markers nor frailty/dependency was associated with survival. Our preliminary study suggests that immuno-senescence markers, but not inflammaging or functional capacity, are associated with survival beyond 100 years in a small group of Cuban centenarians.
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Imunossenescência , Idoso de 80 Anos ou mais , Humanos , Antígenos CD28 , Centenários , Linfócitos T , Envelhecimento , BiomarcadoresRESUMO
Aging of people with human immunodeficiency virus (HIV) is a worldwide reality, and age-related conditions, including disability, have also increased. Efforts are being made to search for more specific markers of immune system malfunction, which serve as good predictors of adverse health-related outcomes. Therefore, this study aimed to determine the relationship between the CD4+/CD8+ ratio and functional decline in activities of daily living (ADL). Participants in this longitudinal study underwent a standardized comprehensive geriatric assessment by trained staff, using validated tools. Functional decline in ADL was established by the delta resulting from the subtraction of the score on the Barthel index at T1 minus the score at T0 (baseline). Multivariate linear regression analyses were used to determine the independent relationship between the CD4+/CD8+ ratio and ADL decline. Mean age was 57.9 (standard deviation 6.6; range 50-84 years), and 82.7% were men. Eleven of the 209 participants had disability for ADL at baseline. Multivariate linear regression analysis showed an inverse relationship between the log of CD4+/CD8+ ratio at baseline and the delta of Barthel index even after adjustment for multiple confounders (ß = -1.68, 95% confidence interval -3.02 to -0.33; p = .01). A CD4+/CD8+ ratio of <1 predicts the development of functional decline in ADL. This ratio can be a useful marker to identify people at risk of disability and should be considered for the tailored management of older adults with HIV.
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Atividades Cotidianas , Infecções por HIV , Masculino , Idoso , Humanos , Pessoa de Meia-Idade , Feminino , Estudos Longitudinais , Avaliação Geriátrica/métodos , Linfócitos T CD4-Positivos , Linfócitos T CD8-Positivos , Fatores de RiscoRESUMO
OBJECTIVES: To assess the effect of protease inhibitor (PI)-based dual therapy on CD4/CD8 ratio during the first year of therapy in antiretroviral therapy (ART)-naïve patients using data from randomized controlled clinical trials. METHODS: We pooled data from the GARDEL and ANDES studies, both randomized controlled clinical trials that recruited ART-naïve people living with HIV and randomly assigned them to receive PI-based dual therapy (DT) or triple therapy (TT) aiming to compare viral efficacy. We compared median CD4/CD8 ratios and the proportion of patients with CD4/CD8 ratio > 1 at 48 weeks after ART initiation in both treatment arms using the Mann-Whitney U-test and the χ2 test. We performed subgroup analysis for patients > 50 years old, with baseline CD4 counts ≤ 200 cells/µL, viral load > 100 000 HIV RNA copies/mL, and ritonavir-boosted lopinavir-based therapy. RESULTS: We analysed data from 571 patients: 292 on DT and 279 on TT. No differences were observed in CD4/CD8 ratio (0.632 vs. 0.617, P = 0.729) or in the proportion of patients with CD4/CD8 ratio > 1 (17.9% vs. 19.3%, P = 0.678) 48 weeks after ART initiation. Subgroup analysis showed no further differences. CONCLUSION: The impact of PI-based DT regimens on the CD4/CD8 ratio during the first year of treatment for ART-naïve patients is similar to that of TT.
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Fármacos Anti-HIV , Infecções por HIV , Inibidores da Protease de HIV , HIV-1 , Contagem de Linfócito CD4 , Linfócitos T CD8-Positivos , Infecções por HIV/tratamento farmacológico , Humanos , Lamivudina/uso terapêutico , Pessoa de Meia-Idade , Inibidores da Transcriptase Reversa , Ritonavir/farmacologia , Ritonavir/uso terapêutico , Carga ViralRESUMO
RESUMEN Objetivo: las personas infectadas con el virus de la inmunodeficiencia humana tipo 1 (VIH-1+) con un índice CD4:CD8 menor a 1, presentan un mayor riesgo de morbilidad y mor-talidad por eventos no asociados con el SIDA. El objetivo de este trabajo fue explorar‚ en la población seleccionada‚ variables sociodemográficas y clínicas de acuerdo con dicho índice, debido a que este es más informativo que LT CD4+ y LT CD8+ por sí solos. Materiales y métodos: estudio observacional en pacientes con VIH-1+ atendidos en la Corporación para Investigaciones Biológicas (CIB). En 227 pacientes se evaluaron diferencias en edad‚ recuento de LT CD4+‚ carga viral‚ número y tipo de esquemas. Se dividieron los pacientes en dos grupos: (A con índice CD4:CD8 ≥ 1 y, B < 1). Resultados: el estudio se compuso de la siguiente forma, 71 % hombres y 29 % mujeres. El 22,5 % pertenecía al grupo A y el 77,5 % al B. La media de la edad fue 42‚8 años en el grupo A y 45 en el B (p = 0‚176). El 100 % de los individuos en el grupo A recibían tratamiento y, 97‚7 % en el B. La media de LT CD4+ fue de 772‚4 para el grupo A y, 448‚1 en el B (p = 0‚00001). En el grupo A el 90‚2 % tenían carga viral indetectable‚ en contraste con el 68‚8 % del B (p = 0‚002). El 41‚2 % en el grupo A tuvieron un solo esquema‚ en relación con el 43,8 % del B (p = 0‚744). Conclusiones: la mayoría de los pacientes presentaron un índice CD4:CD8 < 1 a pesar de haber presentado LT CD4+ aceptables. Fue más frecuente encontrar un índice < 1 en los pacientes sin un adecuado control virológico. Se requieren más estudios para determinar las variables asociadas con su normalización.
SUMMARY Introduction: Human Immunodeficiency Virus type 1 (HIV-1+) patients with a CD4:CD8 ratio < 1 presents a higher risk of morbidity and mortality due to not-associated AIDS events. The aim was to explore, in the selected population, sociodemographic and clinical variables, based on that ratio, because it is more informative than LT CD4+ and LT CD8+ by themselves. Materials and Methods: Observational, in HIV-1 infected patients attended at Biological Research Corporation. In 227 patients, age differences, LT CD4+ count, viral load, number and type of treatments were evaluated. The patients were divided in group A with a CD4:CD8 ratio equal or above to 1, and B bellow 1. Results: The study includes 71% of male and 29% of female. 22,5% were from group A and 77,5% from B. The mean of age was 42,8 years old in A and 45,3 years old in B (p=0,176). 100% of individuals from group A receive treatment, meanwhile 97,7% in B. Mean of LT CD4+ count was 772,4 cell/μL in A and 448,1 cell/μL in B (p=0,00001). In A, 90,2% had undetectable viral load vs 68,8% in B (p=0,002). 41,2% in A had only one type of treatment, vs 43,8% in B (p=0,744). Conclusion: Most of the patients had a CD4:CD8 ratio bellow to 1, despite an acceptable count of LTCD4++. To find a ratio bellow 1 in patients without an adequate virological control was more frequent. More studies to determinate variables associated with its normalization are required.
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Humanos , Antígenos CD4 , Síndrome da Imunodeficiência Adquirida , HIV , Antígenos CD8 , MortalidadeRESUMO
The progression of the human immunodeficiency virus (HIV) infection to acquired immunodeficiency syndrome (AIDS) can be efficiently interrupted by antiretroviral therapy (ART). However, even successfully treated HIV-infected individuals are prone to develop non-AIDS-related diseases that affect the metabolism and several organs and systems. Biomarkers that predict the occurrence of comorbidities may help develop preventive measures. Current research shows that CD4+ T cell counts and viral load do not predict the development of non-AIDS-related diseases. The CD4/CD8 ratio has been indicated as a suitable marker of persistent immune dysfunction and the occurrence of non-AIDS-related events in treated HIV-positive patients. In this study, we explored the relationship between CD4/CD8 ratios, comorbidities, and aging in ART-treated HIV patients on viral suppression. We collected and evaluated data from 352 HIV-positive adults who were virologically suppressed (<40 copies/mL) on ART and with CD4 counts above 350 cells/mm3 . The median age for participants was 46 years, 218 individuals had at least one comorbidity, and 239 had inverted CD4/CD8 ratios (<1). Current CD4/CD8 ratios were predicted by baseline CD4/CD8 ratios and nadir CD4 counts. Despite the high rates of inverted CD4/CD8 ratios and prevalence of comorbidities, no association between them was observed. The prevalence of comorbidities was significantly higher in older individuals, though aging alone did not explain the rate of all individual comorbidities. Low CD4/CD8 ratios were linked to neurocognitive disorders, suggesting that persistent T cell dysfunction contributes to neurocognitive decline.
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Resumen Introducción : los inflamasomas dirigen la maduración de las citoquinas IL-1b e IL-18, las cuales contribuyen en la patogénesis de la infección por VIH-1. Dada la complejidad de la infección, se hace necesaria la búsqueda de marcadores que permitan identificar nuevos blancos terapéuticos o hacer seguimiento del estado inmunológico de los pacientes. Por lo tanto, el objetivo del presente trabajo fue explorar el efecto independiente de los principales componentes inflamatorios sobre la infección por VIH-1. Materiales y métodos : estudio analítico con 36 pacientes VIH+ y 36 controles sanos, pareados por edad y sexo. Se cuantificó la carga viral, los linfocitos T CD4+/CD8+, el perfil lipídico, la proteína C reactiva y las concentraciones séricas de IL-1-ß, IL-6 e IL-18. El HIRNA de los genes relacionados con los inflamasomas fue cuantificado por RT-PCR en tiempo real. El análisis estadístico se basó en medidas de resumen, pruebas de hipótesis y regresión logística binaria multivariante. Resultados : se encontraron menores valores de HDL y HIRNA IL-18 y mayores de HIRNA NLRPI y HIRNA ASC en los pacientes con VIH-1, comparados con los controles. Los valores de HDL y HIRNA IL-18 se correlacionaron con los recuentos de linfocitos. En el análisis multivariado se encontró que la relación CD4/CD8, el mRNA IL-18 y el HIRNA ASC pueden constituir las principales variables que tienen un potencial explicativo sobre la infección por VIH-1 en la población de estudio. Conclusión : se evidenció la importancia de estudiar los inflamasomas, dado que en la población de estudio constituyen potenciales blancos terapéuticos para disminuir la respuesta inflamatoria.
Abstract Introduction : Inflammasomes direct the maturation of the cytokines IL-1ß and IL-18, which contribute to the pathogenesis of HIV-1 infection. Given its complexity, it is necessary to search for markers that can identify new therapeutic targets or monitor the immunological status of patients. Therefore, the objective of the present work was to explore the independent effect of the main inflammatory components on HIV-1 infection. Materials and Methods : Researchers conducted an analytical study with 36 HIV+ patients and 36 healthy controls, matched by age and sex. Viral load, CD4+/CD8+ T lymphocytes, lipid profile, C-reactive protein and serum concentrations of IL-1ß, IL-6, and IL-18 were quantified. RT-PCR in real time quantified the ITIRNA of the genes related to the inflammasomes. The statistical analysis based on summary measures, hypothesis tests, and multivariate binary logistic regression. Results : Lower values of HDL and ITIRNA IL-18 and higher ITIRNA NLRPI and ITVRNA ASC presented in patients with HIV-1 compared with controls. The values of HDL and ITIRNA IL-18 correlated with lymphocyte counts. The multivariate analysis shows that the CD4 / CD8 ratio, the IL-18 ITIRNA and the ASC ITIRNA can be the main variables that have an explanatory potential on HIV-1 infection in the study population. Conclusion : The importance of studying inflammasomes was evidenced, given that in the study population they are potential therapeutic targets to reduce the inflammatory response.
Resumo Introdução : os inflamassomas dirigem a maduração das citocinas IL-1ß e IL-18; as quais contribuem nas patogêneses da infeção por HIV-1. Dada a complexidade da infeção se faz necessária a busca de marcadores que permitam identificar novos alvos terapêuticos ou fazer seguimento do estado imunológico dos pacientes. Portanto, o objetivo do presente trabalho foi explorar o efeito independente os principais componentes inflamatórios sobre a infeção por HIV-1. Materiais e métodos : estudo analítico com 36 pacientes HIV+ e 36 controles saudáveis, pareados por idade e sexo. Se quantificou a carga viral, os linfócitos T CD4+/CD8+, o perfil lipídico, a proteína C reativa e as concentrações séricas de IL-1ß, IL-6 e IL-18. O ITIRNA dos genes relacionados com os inflamassomas foi quantificado por RT-PCR em tempo real. A análise estatística se baseou em medidas de resumo, provas de hipótese e regressão logística binaria multivariado. Resultados : se encontraram menores valores de HDL e TÍTRNA IL-18 e maiores de TÍIRNA NLRPI e TÍTRNA ASC nos pacientes com HIV-1, comparados com os controles. Os valores de HDL e TÍTRNA IL-18 se correlacionaram com os recontos de linfócitos. Na análise multivariada encontrou-se que a relação CD4/CD8, o TÍIRNA IL-18 e o TÍTRNA ASC podem constituir as principais variáveis que têm um potencial explicativo sobre a infeção por HIV-1 na população de estudo. Conclusão : se evidenciou a importância de estudar os inflamassomas, dado que na população de estudo constituem potenciais brancos terapêuticos para diminuir a resposta inflamatória.
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Humanos , HIV-1 , Análise Multivariada , Relação CD4-CD8 , Colômbia , Inflamassomos , Estudo ObservacionalRESUMO
Abstract INTRODUCTION: The objective was to identify comorbidities related to HIV-positive patients in Blumenau, State of Santa Catarina. METHODS: A retrospective, descriptive observational design study which analyzed data from 424 patients assisted by the sexually transmitted disease/acquired immunodeficiency syndrome (STD/AIDS) Specialized Care Service (SCS). RESULTS: Of 424 medical records analyzed, 388 patients presented CD4+/CD8+ ratios lower than 1. The most prevalent comorbidities were smoking, depression, alcoholism, and herpes zoster infection, in males and females. CONCLUSIONS: The most relevant comorbidity in both genders was herpes zoster, an important marker of immunity in patients. The lowest mean was observed among patients with neurotoxoplasmosis.
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Humanos , Masculino , Feminino , Adulto , Adulto Jovem , Síndrome da Imunodeficiência Adquirida/sangue , Síndrome da Imunodeficiência Adquirida/epidemiologia , Relação CD4-CD8/estatística & dados numéricos , Valores de Referência , Brasil/epidemiologia , Fumar/sangue , Fumar/epidemiologia , Comorbidade , Prevalência , Estudos Retrospectivos , Fatores de Risco , Distribuição por Sexo , Depressão/sangue , Depressão/epidemiologia , Alcoolismo/sangue , Alcoolismo/epidemiologia , Herpes Zoster/sangue , Herpes Zoster/epidemiologia , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Hepatitis B virus (HBV) and human immunodeficiency virus (HIV) share transmission mechanisms and thus coinfection is frequent. Active immunization against HBV is essential in HIV patients. Reports using standard and reinforced HBV vaccination schedules vary widely in seroconversion rates depending on the characteristics of the included patients. Regional data concerning HBV vaccination in HIV patients are scarce. We aim to determine the serological response to HBV vaccination using standard schedule in HIV-positive patients and to evaluate characteristics that predict seroconversion. MATERIALS AND METHODS: We performed a single centre prospective study of HBV vaccination with standard schedule in HIV-positive patients. Adults with negative markers of HBV infection were included between November 2012 and December 2014. Anti-HBs titres were measured 4-8 weeks after completion of vaccination schedule. Clinical, laboratory values and HIV characteristics were analyzed to determine their association with seroconversion and adherence to the HBV vaccination schedule. RESULTS: The study included 245 HIV-positive patients, 68.9% were male and the mean age was 42.1 years. A total of 80.7% of the patients had undetectable HIV viral loads, 86.1% had CD4 counts >200, and 94.7% were on HAART. The response to vaccination was positive in 62% (95% CI, 56-68%) and mean anti-HBs titres of 646 IU/ml. 85.5% of the responders had anti-HBs titres >100 IU/ml. An age less than 45 years, no tobacco use and a CD4/CD8 ratio >0.4 were associated with seroconversion in multivariate analysis. The seroconversion rates were 86% in the subgroup of patients who met these criteria. A total of 97.9% of the study population completed the vaccination schedule. CONCLUSION: The CD4/CD8 ratio was the primary factor associated with positive serological conversion in the multivariate analysis. The seroconversion rates were higher in a selected group of patients who were particularly suitable for the use of the standard HBV vaccination schedule.
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Relação CD4-CD8 , Soropositividade para HIV , Vacinas contra Hepatite B/uso terapêutico , Hepatite B/prevenção & controle , Adulto , Formação de Anticorpos , Feminino , Infecções por HIV/imunologia , Anticorpos Anti-Hepatite B/sangue , Vacinas contra Hepatite B/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , SoroconversãoRESUMO
Objetivos: Avaliar a migração de neutrófilos e a frequência relativa de linfócitos CD4+/CD8+ em crianças com síndrome de Down e controles saudáveis.Métodos: Este foi um estudo de caso-controle realizado no Instituto de Pesquisas Biomédicas, no Hospital São Lucas da PUCRS. Os pacientes do grupo de estudo foram selecionados por uma amostragem de conveniência, representando todas as crianças com síndrome de Down e idade entre três e 13 anos, que frequentavam os ambulatórios de Pediatria e de Otorrinolaringologia do Hospital São Lucas da PUCRS e do Kinder - Centro de Integração da Criança Especial, em Porto Alegre, Rio Grande do Sul, nos meses de janeiro e dezembro de 2012. Para o grupo controle foram recrutadas crianças saudáveis e sem síndrome de Down, participantes de outro estudo em andamento no Instituto de Pesquisas Biomédicas. Foram selecionados os pacientes com maior volume de células armazenadas em criotubos. Para avaliar os parâmetros da resposta imune, foram realizados ensaio de quimiotaxia de neutrófilos e imunofenotipagem de células T CD4+ e CD8+. Associações foram avaliadas pelo teste do qui-quadrado, t de Student ou Mann-Whitney. Todos os testes foram bidirecionais e as diferenças foram consideradas significativas quando p menor que 0,05.Resultados: Foram incluídos 19 pacientes (13 com síndrome de Down e seis controles), com médias de idade de 8,13 e 9,83 anos, respectivamente. Não foram observadas alterações significativas no grupo com síndrome de Down em relação à capacidade de migração dos neutrófilos. Houve uma tendência a valores percentuais menores de células T CD4+ e maiores de CD8+ para o grupo com síndrome de Down. Houve diferença significativa na relação CD4+/CD8+ entre os dois grupos, sendo a mesma menor no grupo com síndrome de Down.Conclusões: Este estudo sugere que os pacientes com síndrome de Down apresentam uma taxa CD4+/CD8+ diminuída, o que pode contribuir para as infecções frequentes e recorrentes nessas crianças.
Aims: To evaluate neutrophil migration and the relative frequency of CD4+/CD8+ lymphocytes in children with Down syndrome and in healthy controls.Methods: This was a case-control study carried out at the Institute of Biomedical Research, affiliated with São Lucas Hospital of the Pontifical Catholic University of Rio Grande do Sul (PUCRS). Patients with Down syndrome were selected by convenience sampling, including all children with Down syndrome aged 3 to 13 years treated at the Pediatric and Otolaryngology Outpatient Clinics of São Lucas Hospital and at Kinder - Center for Children with Special Needs, in Porto Alegre, State of Rio Grande do Sul, Brazil, between January and December 2012. Healthy children without Down syndrome, participants in another ongoing study conducted by Institute of Biomedical Research, were recruited to the control group. Those patients with the largest volume of cells stored in cryotubes were selected. A neutrophil chemotaxis assay and immunophenotyping of CD4+ and CD8+ T cells were performed to evaluate the functionality of the immune response. Associations were assessed by the chi-squared test, Student's t test, or Mann-Whitney's test. All tests were bidirectional, and p values less than 0.05 were regarded as statistically significant.Results: This study included 19 patients (13 with Down syndrome and six controls), with a mean age of 8.13 and 9.83 years, respectively. No significant changes concerning neutrophil migration were observed in the Down syndrome group. However, patients with Down syndrome tended to have a lower rate of CD4+ T cells and a higher rate of CD8+ T cells. The CD4+/CD8+ ratio revealed significant difference between the groups, being lower in patients with Down syndrome.Conclusions: This study suggests that patients with Down syndrome show a decreased CD4+/CD8+ ratio, which may contribute to the frequent and recurrent infections in these children.