RESUMEN
This study investigated the association between serum albumin concentration and 12-weeks mortality of HIV/AIDS with late diagnosis in China. This retrospective cohort study included, 1079 inpatients diagnosis with late HIV/AIDS between January 2018 and December 2021. Disease progression was estimated based on the 12-weeks mortality rate. Cox proportional hazards regression models were used to evaluate the relationship between serum albumin levels and disease progression. The effects of serum albumin levels on mortality was estimated via Kaplan-Meier curves. The mortality risk decreased by 7% with every 1 g/L increase in serum albumin after adjustment ([HR] = 0.93, 95% CI: 0.88-0.97). Compared with that of the low (< 28 g/L) serum albumin group, the middle (28-34 g/L) group's mortality risk decreased by 70% (HR = 0.30, 95% CI: 0.15-0.59), and that of the high (≥ 34 g/L) group decreased by 40% (HR = 0.6, 95% CI: 0.29-1.23) after adjustment. Our findings suggest a positive correlation between the increase in serum albumin levels upon admission and a decrease in mortality at 12 weeks post-discharge among patients with late AIDS/HIV diagnosis. Further research is needed to characterize the role of serum albumin in 12-weeks mortality prevention in patients with a late diagnosis.
Asunto(s)
Síndrome de Inmunodeficiencia Adquirida , Albúmina Sérica , Humanos , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Adulto , Albúmina Sérica/análisis , Síndrome de Inmunodeficiencia Adquirida/mortalidad , Síndrome de Inmunodeficiencia Adquirida/sangre , Síndrome de Inmunodeficiencia Adquirida/diagnóstico , Infecciones por VIH/mortalidad , Infecciones por VIH/sangre , Infecciones por VIH/diagnóstico , China/epidemiología , Modelos de Riesgos Proporcionales , Progresión de la Enfermedad , Diagnóstico Tardío , Estimación de Kaplan-MeierRESUMEN
BACKGROUND: Antiretroviral therapy (ART) was often associated with dyslipidemia among human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) patients. This study aimed to assess treatment-naïve adult male patients with HIV/AIDS who initiated ART with either co-formulated bictegravir, emtricitabine, and tenofovir alafenamide (BIC/FTC/TAF) or lamivudine, efavirenz, and tenofovir disoproxil fumarate (3TC+EFV+TDF), monitoring at weeks 4, 12, 24, and 48. METHODS: A case-control retrospective study was conducted. The newly diagnosed HIV-infected individuals attending the sexual transmission disease (STD)/AIDS clinic of Beijing Youan Hospital, Capital Medical University, from January to December 2021. The patients were divided into BIC/FTC/TAF group or 3TC+EFV+TDF group. High-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), and total cholesterol (TC) at different time points over 48 weeks between two groups were compared. A multivariate Cox regression model was used to identify relevant influencing factors for the population at high risk of increased LDL-C. RESULTS: A total of 870 participants, with 510 in BIC/FTC/TAF group and 360 in 3TC+EFV+TDF group. There were no statistically significant differences in median age, baseline CD4/CD8 ratio, median body mass index (BMI) between the two groups. In both two groups, levels of TG, TC, and LDL-C were higher at 4 weeks, 12 weeks, and 24 weeks of treatment (all P <0.05), and there were no statistically significant differences at 48 weeks compared to those at baseline (all P >0.05). In addition, the differences in average changes of the level of TG, TC, HDL-C, and LDL-C from weeks 4, 12, 24, and 48 to baseline between two groups were not statistically significant (all P >0.05). Multivariate Cox proportional risk model analysis showed that initiating ART with HIV RNA ≥10 5 copies/mL (compared with <10 5 copies/mL) was associated with an increased risk of elevated LDL-C (hazard ratio = 1.26, 95% confidence interval: 1.07-1.48, P = 0.005). CONCLUSIONS: Transient elevations in blood lipid levels (TC, TG, HDL-C, and LDL-C) were observed in treatment-naïve adult male HIV/AIDS patients with BIC/FTC/TAF at 4 weeks, 12 weeks, and 24 weeks of treatment. However, these levels did not differ significantly from baseline after 48 weeks of treatment, regardless of whether patients were in the BIC/FTC/TAF or 3TC+EFV+TDF group.
Asunto(s)
Infecciones por VIH , Lamivudine , Lípidos , Tenofovir , Humanos , Masculino , Adulto , Estudios Retrospectivos , Lamivudine/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/sangre , Tenofovir/uso terapéutico , Estudios de Casos y Controles , Lípidos/sangre , Fármacos Anti-VIH/uso terapéutico , Persona de Mediana Edad , Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Síndrome de Inmunodeficiencia Adquirida/sangre , Triglicéridos/sangre , Emtricitabina/uso terapéuticoRESUMEN
BACKGROUND: In clinical practice, Measurement of estimated glomerular filtration rates (eGFR) is the gold standard assessing renal function the glomerular filtration rate often estimated from plasma creatinine. Several studies have shown Cystatin C based eGFR (Cys C) to be a better parameter for the diagnosis of impaired renal function. Cystatin C based eGFR has been proposed as a potential renal function marker but its use in HIV&AIDS patients has not been well evaluated. METHODS: A cross sectional study was carried out on 914 HIV&AIDS patients on antiretroviral therapy (ART) attending Mildmay Uganda for care and treatment between January to March 2015. Serum Cystatin C based eGFR was measured using the particle enhanced immunoturbidimetric assay. Creatinine was analyzed using enzymatic Creatinine PAP method and creatinine clearance was calculated according to C&G. RESULTS: The sensitivity of Cystatin C based eGFR was 15.1% (95% CI = 8.4, 24) with specificity 99.3% (95% CI = 98- 99.7). The positive and negative predictive values were 70.0% (95% CI 45.7-88.1) and 91.2% (95% CI 98.11-92.94) respectively. The positive likelihood ratio was 18.81 and negative likelihood ratio was 0.85. Cystatin C based eGFR had diagnostic accuracy of 90.7 and area under curve was 0.768. CONCLUSION: Cystatin C based eGFR exhibited a high specificity and a high positive likelihood ratio in diagnosis of kidney disease among HIV&AIDS patients. Cystatin C based eGFR can be used as a confirmatory test.
Asunto(s)
Cistatina C , Tasa de Filtración Glomerular , Infecciones por VIH , Humanos , Cistatina C/sangre , Uganda , Masculino , Femenino , Adulto , Estudios Transversales , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/sangre , Infecciones por VIH/complicaciones , Persona de Mediana Edad , Biomarcadores/sangre , Síndrome de Inmunodeficiencia Adquirida/sangre , Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Creatinina/sangre , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: C-reactive protein (CRP) is an inflammatory biomarker associated with all-cause mortality and morbidities such as cardiovascular disease. CRP is increased with HIV infection and thought to increase with age, though trajectories of CRP with aging have not been well characterized. We investigated trajectories of CRP in men from the Multicenter AIDS Cohort Study, according to HIV infection and HIV viral load status. METHODS: CRP measurements from 12 250 serum samples, provided by 2132 men over a span of 30 years, were categorized by HIV status at sample collection: HIV uninfected (HIV-, n = 1717), HIV infected with undetectable RNA (HIV+ suppressed, n = 4075), and detectable HIV RNA (HIV+ detectable, n = 6458). Age-related trajectories of CRP were fit to multivariable linear mixed models; we tested for differences in trajectories by HIV status. RESULTS: CRP increased with age in all sample groups. HIV+ detectable and HIV+ suppressed samples had higher CRP than HIV- samples throughout the observed age range of 20-70 years (p < .05). CRP concentrations at age 45 years were 38% (95% CI: 26%-50%) and 26% (15%-38%) higher in HIV+ detectable and HIV+ suppressed samples, respectively, relative to HIV- samples. HIV+ detectable samples showed more rapid linear increases with age (8% higher/decade, 0.3%-16%) than HIV- samples. CONCLUSIONS: We observed higher concentrations of CRP across 5 decades of age in men living with HIV, and steeper increases with age in men with detectable HIV RNA, relative to HIV- men. These results are consistent with a contribution of inflammation to the higher risk of age-related comorbidities with HIV infection.
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Proteína C-Reactiva , Infecciones por VIH , Inflamación , Síndrome de Inmunodeficiencia Adquirida/sangre , Síndrome de Inmunodeficiencia Adquirida/complicaciones , Adulto , Anciano , Biomarcadores/sangre , Proteína C-Reactiva/análisis , Estudios de Cohortes , Infecciones por VIH/sangre , Infecciones por VIH/complicaciones , Humanos , Inflamación/sangre , Masculino , Persona de Mediana Edad , ARN , Adulto JovenRESUMEN
A late presenter AIDS patient with severe T cell depletion presented non-severe COVID-19 symptoms, with prolonged viral shedding. Our case report supports the hypothesis that an effective T cell response may be dispensable for the control of COVID-19 progression to severe forms, while it may be necessary for SARS-CoV-2 clearance.
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Síndrome de Inmunodeficiencia Adquirida/inmunología , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , COVID-19/inmunología , SARS-CoV-2/inmunología , Síndrome de Inmunodeficiencia Adquirida/sangre , Adulto , Recuento de Linfocito CD4 , Linfocitos T CD4-Positivos/metabolismo , Linfocitos T CD8-positivos/metabolismo , COVID-19/sangre , Femenino , Humanos , SARS-CoV-2/metabolismoRESUMEN
Low nadir CD4 T-cell counts in HIV+ patients are associated with high morbidity and mortality and lasting immune dysfunction, even after antiretroviral therapy (ART). The early events of immune recovery of T cells and B cells in severely lymphopenic HIV+ patients have not been fully characterized. In a cohort of lymphopenic (CD4 T-cell count < 100/µL) HIV+ patients, we studied mononuclear cells isolated from peripheral blood (PB) and lymph nodes (LN) pre-ART (n = 40) and 6-8 weeks post-ART (n = 30) with evaluation of cellular immunophenotypes; histology on LN sections; functionality of circulating T follicular helper (cTfh) cells; transcriptional and B-cell receptor profile on unfractionated LN and PB samples; and plasma biomarker measurements. A group of 19 healthy controls (HC, n = 19) was used as a comparator. T-cell and B-cell lymphopenia was present in PB pre-ART in HIV+ patients. CD4:CD8 and CD4 T- and B-cell PB subsets partly normalized compared to HC post-ART as viral load decreased. Strikingly in LN, ART led to a rapid decrease in interferon signaling pathways and an increase in Tfh, germinal center and IgD-CD27- B cells, consistent with histological findings of post-ART follicular hyperplasia. However, there was evidence of cTfh cells with decreased helper capacity and of limited B-cell receptor diversification post-ART. In conclusion, we found early signs of immune reconstitution, evidenced by a surge in LN germinal center cells, albeit limited in functionality, in HIV+ patients who initiate ART late in disease.
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Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Fármacos Anti-VIH/uso terapéutico , Linfocitos B/inmunología , Centro Germinal/inmunología , Subgrupos Linfocitarios/inmunología , Linfocitos T Colaboradores-Inductores/inmunología , Viremia/tratamiento farmacológico , Síndrome de Inmunodeficiencia Adquirida/sangre , Síndrome de Inmunodeficiencia Adquirida/inmunología , Adulto , Fármacos Anti-VIH/farmacología , Anticuerpos Antivirales/sangre , Técnicas de Cocultivo , Femenino , Centro Germinal/patología , Hemoglobinas/análisis , Humanos , Hiperplasia , Ganglios Linfáticos/inmunología , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Receptores de Antígenos de Linfocitos B/genética , Transcripción Genética , Carga Viral , Viremia/inmunología , Adulto JovenRESUMEN
OBJECTIVE: To investigate the quantity of CD4+T, CD4+T, CD8+T, and γδT cells in peripheral blood of HIV-infected/AIDS patients as well as to explore the possible role of CD4/CD8 ratio and γδT cells in the progression of HIV/AIDS, aimed at providing evidence for the diagnosis and treatment of AIDS. METHODS: The quantity levels of CD3+T cells, CD4+T cells, CD8+T cells, and γδT cells in peripheral blood of 46 HIV-infected/AIDS patients and 30 healthy controls were detected by using flow cytometry. RESULTS: The count of CD3+T, CD4+T, CD8+T, and γδT cells ( x ¯ ± s , A/µl) in the peripheral blood was 1183.64 ± 132.58, 278.39 ± 122.38, 863.13 ± 82.38, and 22.53 ± 1.74 in the experimental group as well as 1456.46 ± 124.37, 788.74 ± 189.67, 569.61 ± 46.49, and 10.96 ± 0.28 in the control group, respectively. The p values of the two groups were <0.005 after the t-test, revealing a statistically significant difference. The proportion of CD3+T, CD4+T, CD8+T, and γδT cells in total lymphocytes in the two groups ( x ¯ ± s , %) was 71.83 ± 5.37, 13.39 ± 2.23, 62.93 ± 5.81, and 3.67 ± 0.87 in the experimental group, respectively. In the control group, the values were expressed as 66.72 ± 5.48, 42.77 ± 3.38, 31.41 ± 3.62, and 1.73 ± 0.36, respectively. After performing the t-test, p values in the two groups were <0.005 except CD3+T, with statistically significant differences. Besides, CD4/CD8 was 0.33 ± 0.11 in the experimental group and 1.48 ± 0.29 in the control group, t = 26.528, p < 0.001, exhibiting a significant statistical difference. CONCLUSION: HIV infection induces the activation and proliferation of CD8+T and γδT cells, contributing to the decrease of CD4+T cells, while CD8+T and γδT cells are involved in the immune response and tissue damage after HIV infection.
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Síndrome de Inmunodeficiencia Adquirida/inmunología , Infecciones por VIH/inmunología , Subgrupos de Linfocitos T/clasificación , Subgrupos de Linfocitos T/inmunología , Síndrome de Inmunodeficiencia Adquirida/sangre , Adulto , Anciano , Complejo CD3/sangre , Recuento de Linfocito CD4 , Relación CD4-CD8 , Estudios de Casos y Controles , Proliferación Celular , Biología Computacional , Femenino , Infecciones por VIH/sangre , Humanos , Activación de Linfocitos , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Receptores de Antígenos de Linfocitos T gamma-delta/sangre , Adulto JovenRESUMEN
BACKGROUND: Previous studies concerning the effect of plasma hemoglobin (HB) and other factors that may modify the risk of death in people living with HIV/AIDS (PLHIV) treated with antiretroviral therapy (ART) are limited. RESULTS: Higher HB was independently linked to a lower death risk in PLHIV, with a decrease of 29% (13%, 43%) per standard deviation (SD) increment after adjusting for CD4, VL and other potential factors [hazard ratio (HR): 0.71, 95% confidence interval (CI): 0.57-0.87, P<0.001]. In addition, the addition of HB to the predictive model containing VL and CD4 significantly improved the C-index, by 0.69% (95% CI: 0.68%-0.71%), and net discrimination, by 0.5% (95% CI: 0.0%-1.6%, P=0.040), when predicting the death risk of PLHIV. CONCLUSIONS: A lower level of HB was an independent risk factor for HIV/AIDS-associated death in PLHIV. HB combined with VL and CD4 may be an appropriate predictive model of the death risk of PLHIV. MATERIALS AND METHODS: A propensity-score matching (PSM) approach was applied to select a total of 750 PLHIV (150 deceased and 600 living) from the AIDS prevention and control information system in the Wenzhou area from 2006 to 2018. Multivariable Cox proportional hazards regression models were formulated to estimate the effect of HB. The predictive performance improvement contributed by HB was evaluated using the C-index and net reclassification improvement.
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Síndrome de Inmunodeficiencia Adquirida/sangre , Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Antirretrovirales/farmacología , Hemoglobinas/metabolismo , Adulto , Femenino , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , Humanos , Masculino , Modelos de Riesgos Proporcionales , Factores de RiesgoRESUMEN
Mongolia has a low incidence of human immunodeficiency virus (HIV) infection, with 281 cases reported at the end of 2019 and an estimated incidence rate of <0.01 cases per 1000 population. However, no study has analyzed the association between antiretroviral therapy (ART) outcomes and pretreatment characteristics of patients with HIV/acquired immunodeficiency syndrome (AIDS) in Mongolia. This retrospective study aimed to determine the survival, CD4 T cell recovery, and immune reconstitution pattern during ART in HIV patients and to determine baseline patient characteristics associated with ART outcomes. Based on three different World Health Organization (WHO) guidelines, we analyzed the 3-year observation data of 166 patients with HIV/AIDS who received treatment between 2010 and 2017. An increase of >50 cells/µL indicated CD4 T cell count recovery, and a cell count of ≥500 cells/µL in patients with a baseline cell count of <500 cells/µL indicated immune reconstitution. In this study, the 3- and 1-year mortality rates were 5.4% (survival rate: 94.6%) and 3.6%, respectively. A total of 83% of deaths that occurred in the observation time occurred within the first 3 months. The CD4 T cell count recovery rates at 3, 12, and 36 months were 62.7%, 80.7%, and 89.2%, respectively. The CD4 T cell count increased to >500 cells/µL in 95 of 145 (65.5%) patients with a baseline cell count of <500 cells/µL after 36 months of ART. The baseline CD4 T cell count was found to be a sensitive indicator for immune reconstitution. An advanced pretreatment clinical stage of HIV infection (as classified by the WHO classification), a low CD4 T cell count in the peripheral blood, and a high viral load before the initiation of the first-line ART accurately predicted survival, CD4 T cell count recovery, and immune reconstitution in Mongolian patients with HIV/AIDS.
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Síndrome de Inmunodeficiencia Adquirida , Antirretrovirales/administración & dosificación , VIH-1 , Síndrome de Inmunodeficiencia Adquirida/sangre , Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Síndrome de Inmunodeficiencia Adquirida/inmunología , Síndrome de Inmunodeficiencia Adquirida/mortalidad , Adolescente , Adulto , Recuento de Linfocito CD4 , Femenino , VIH-1/inmunología , VIH-1/metabolismo , Humanos , Masculino , Mongolia/epidemiología , Estudios RetrospectivosRESUMEN
We investigated the clinical characteristics and outcomes of acquired immunodeficiency syndrome-related Burkitt lymphoma (AIDS-BL). A single-center retrospective study was performed of 78 cases over a 10-year period. The baseline characteristics of enrolled patients included the following: median age, 46 years; median CD4+ T lymphocyte count, 156 cells/µL; advanced stage, 74.3%; > 1 extranodal site, 55.1%; international prognostic index (IPI) > 1, 85.9%; and elevated serum lactate dehydrogenase, 82.1%. The 1-year and 2-year overall survival (OS) rates were 52.2 ± 5.9% and 42.7 ± 6.2%, respectively. A prognostic analysis of 65 patients who had undergone chemotherapy showed that B symptoms (with vs. without fever, night sweat or weight loss), number of extranodal sites (0, 1 vs. > 1), level of serum albumin (≥ 35 g/L vs. < 35 g/L), hemoglobin (≥ 110 g/L vs. < 110 g/L), and IPI score (≤ 2 vs. > 1) were all associated with OS. However, only B symptoms (HR = 4.036, 95% CI 1.821-8.948, p = 0.001), serum albumin level < 35 g/L (HR = 2.131, 95% CI 1.013-4.483, p = 0.046), and chemotherapy without rituximab (HR = 2.286, 95% CI 1.108-4.714, p = 0.025) were independent predictors of OS after multivariate adjustment. Patients with AIDS-BL were likely to present with high-risk features, and their clinical outcomes were relatively poor, especially those with B symptoms and lower serum albumin levels.
Asunto(s)
Síndrome de Inmunodeficiencia Adquirida , Linfoma de Burkitt , Síndrome de Inmunodeficiencia Adquirida/sangre , Síndrome de Inmunodeficiencia Adquirida/complicaciones , Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Síndrome de Inmunodeficiencia Adquirida/mortalidad , Adulto , Anciano , Linfoma de Burkitt/sangre , Linfoma de Burkitt/tratamiento farmacológico , Linfoma de Burkitt/etiología , Linfoma de Burkitt/mortalidad , Recuento de Linfocito CD4 , Supervivencia sin Enfermedad , Femenino , Humanos , L-Lactato Deshidrogenasa/sangre , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Albúmina Sérica Humana/metabolismo , Tasa de SupervivenciaRESUMEN
Antiretroviral treatment (ART) adherence is highlighted in management of patients living with human immunodeficiency virus. In South Korea, ART medication research has rarely been conducted due to the low economic burden associated with government-funded treatment. This cross-sectional study aimed to compare the pill burden impact between ART regimen compliance and HIV-RNA viral load suppression. Data were collected from 2008 to 2016 at a general hospital in South Korea. A total of 210 HIV/AIDS treatment-naïve patients were grouped as follows: single-tablet regimen (STR, one tablet/day), mild pill burden (two-four tablets/day), and heavy pill burden (≥ five tablets/day). Patients were analyzed according to gender, age at index date, medical insurance type, comorbidities, depression, HIV/AIDS disease burden as indicated by HIV-RNA viral load and CD4, and laboratory variables. In a multivariate logistic regression model, the STR group demonstrated adherence 5.10 times more often than the heavy pill burden group. Females and patients with an initial viral load of 500,000 or more were 0.090- and 0.040-fold less adherent to the ART regimen. Among these patients, 95% or more of the MPR group were 7.38 times more likely to have a lower limit of detection (LLOD) of viral load suppression. The highest initial viral load group was 0.090-fold less likely to have an LLOD than the reference group. These results suggest that a single-tablet regimen could improve medication adherence and the clinical virologic outcome. Therefore, general population research on ART adherence and polypharmacy is needed.
Asunto(s)
Síndrome de Inmunodeficiencia Adquirida , Antirretrovirales/administración & dosificación , Cumplimiento de la Medicación , ARN Viral/sangre , Carga Viral , Síndrome de Inmunodeficiencia Adquirida/sangre , Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , República de CoreaRESUMEN
Aflatoxins are carcinogenic mycotoxins that contaminate a variety of crops worldwide. Acute exposure can cause liver failure, and chronic exposure can lead to stunting in children and liver cancer in adults. We estimated aflatoxin exposure across Uganda by measuring a serum biomarker of aflatoxin exposure in a subsample from the 2011 Uganda AIDS Indicator Survey, a nationally representative survey of HIV prevalence, and examined its association with geographic, demographic, and socioeconomic variables. We analysed a subsample of 985 serum specimens selected among HIV-negative participants from 10 survey-defined geographic regions for serum aflatoxin B1-lysine (AFB1-lys) by use of isotope dilution LC-MS/MS and calculated results normalised to serum albumin. We used statistical techniques for censored data to estimate geometric means (GMs), standard deviations, and percentiles. We detected serum AFB1-lys in 71.7% of specimens (LOD = 0.5 pg/mg albumin). Unadjusted GM AFB1-lys (pg/mg albumin) was 1.33 (95% CI: 1.21-1.47). Serum AFB1-lys was higher in males (GM: 1.57; 95% CI: 1.38-1.80) vs. females (GM: 1.12; 95% CI: 0.97-1.30) (P = .0019), and higher in persons residing in urban settings (GM: 2.83; 95% CI: 2.37-3.37) vs. rural (GM: 1.10; 95% CI: 0.99-1.23) (P < .0001). When we used a multivariable censored regression model to assess confounding and interactions among variables we found that survey region, gender, age, occupation, distance to marketplace, and number of meals per day were statistically significant predictors of aflatoxin exposure. While not nationally representative, our findings provide an improved understanding of the widespread burden of aflatoxin exposure throughout Uganda and identify key geographic, demographic, and socioeconomic factors that may modulate aflatoxin exposure risk.
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Síndrome de Inmunodeficiencia Adquirida/sangre , Aflatoxina B1/sangre , Recolección de Muestras de Sangre , Exposición a Riesgos Ambientales/análisis , Encuestas Epidemiológicas , Adolescente , Adulto , Biomarcadores/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
The molecular mechanisms underlying HIV-induced inflammation, which persists even during effective long-term treatment, remain incompletely defined. Here, we studied pathogenic and nonpathogenic simian immunodeficiency virus (SIV) infections in macaques and African green monkeys, respectively. We longitudinally analyzed genome-wide DNA methylation changes in CD4 + T cells from lymph node and blood, using arrays. DNA methylation changes after SIV infection were more pronounced in lymph nodes than blood and already detected in primary infection. Differentially methylated genes in pathogenic SIV infection were enriched for Th1-signaling (e.g., RUNX3, STAT4, NFKB1) and metabolic pathways (e.g., PRKCZ). In contrast, nonpathogenic SIVagm infection induced DNA methylation in genes coding for regulatory proteins such as LAG-3, arginase-2, interleukin-21 and interleukin-31. Between 15 and 18% of genes with DNA methylation changes were differentially expressed in CD4 + T cells in vivo. Selected identified sites were validated using bisulfite pyrosequencing in an independent cohort of uninfected, viremic and SIV controller macaques. Altered DNA methylation was confirmed in blood and lymph node CD4 + T cells in viremic macaques but was notably absent from SIV controller macaques. Our study identified key genes differentially methylated already in primary infection and in tissues that could contribute to the persisting metabolic disorders and inflammation in HIV-infected individuals despite effective treatment.
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Síndrome de Inmunodeficiencia Adquirida/sangre , Síndrome de Inmunodeficiencia Adquirida/genética , Inmunidad/genética , Ganglios Linfáticos/metabolismo , Virus de la Inmunodeficiencia de los Simios/genética , Síndrome de Inmunodeficiencia Adquirida/inmunología , Síndrome de Inmunodeficiencia Adquirida/patología , Animales , Linfocitos T CD4-Positivos/metabolismo , Linfocitos T CD4-Positivos/virología , Chlorocebus aethiops/sangre , Chlorocebus aethiops/genética , Chlorocebus aethiops/virología , Islas de CpG/genética , Metilación de ADN/genética , Epigenómica/métodos , Estudio de Asociación del Genoma Completo/métodos , Infecciones por VIH/genética , Infecciones por VIH/inmunología , Humanos , Ganglios Linfáticos/virología , Macaca mulatta/sangre , Macaca mulatta/genética , Macaca mulatta/virología , Modelos Animales , Virus de la Inmunodeficiencia de los Simios/aislamiento & purificación , Virus de la Inmunodeficiencia de los Simios/patogenicidadRESUMEN
Acquired immunodeficiency syndrome (AIDS) complicated with tuberculosis (TB) is a global public issue. Due to the paucity of bacteria in AIDS/TB, blood-based biomarkers that reflect disease severity are desired. Plasma levels of matricellular proteins, such as osteopontin (OPN) and galectin-9 (Gal-9), are known to be elevated in AIDS and TB. Therefore, full-length (FL)-Gal9 and FL-OPN, and their truncated forms (Tr-Gal9, Ud-OPN), and 38 cytokines/chemokines were measured in the plasma of 24 AIDS (other than TB), 49 TB, and 33 AIDS/TB patients. Receiver-operating characteristic analysis was used to screen molecules that could distinguish either between disease and normal group, among each disease group, or between deceased patients and survivors. Selected molecules were further analyzed for significant differences. Tr-Gal9 had the highest ability to differentiate TB from AIDS or AIDS/TB, while Ud-OPN distinguished multidrug resistance (MDR)-TB from non-MDR TB, and extra-pulmonary TB from pulmonary TB. Molecules significantly elevated in deceased patients included; FL-Gal9, Tr-Gal9, interleukin (IL)-1 receptor antagonist, IL-17A and transforming growth factor-α in AIDS; IL-6, granulocyte colony-stimulating factor and monocyte chemotactic protein-1 in TB; and macrophage inflammatory protein-1ß in AIDS/TB. From the sensitivity, specificity, and significant elevation, Tr-Gal9 is the best biomarker of inflammation and severity in AIDS and AIDS/TB.
Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/sangre , Biomarcadores/sangre , Galectinas/sangre , Tuberculosis/sangre , Síndrome de Inmunodeficiencia Adquirida/complicaciones , Síndrome de Inmunodeficiencia Adquirida/microbiología , Síndrome de Inmunodeficiencia Adquirida/virología , Adulto , Coinfección/sangre , Coinfección/microbiología , Coinfección/virología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/patogenicidad , Osteopontina/genética , Tuberculosis/complicaciones , Tuberculosis/microbiología , Tuberculosis/virologíaRESUMEN
O HIV é o causador da AIDS, doença que representa um dos grandes problemas de saúde pública em todo o mundo. Apesar de avanços na terapia antirretroviral no sentido de aumentar a expectativa de vida dos indivíduos infectados, as alterações hematológicas, como a anemia, acompanham o curso clínico da doença. Essa condição, normalmente multifatorial, pode estar presente em qualquer fase da doença e afeta diretamente o prognóstico e a qualidade de vida do indivíduo infectado. Este artigo apresenta informações do surgimento do processo anêmico com base nas principais causas encontradas na literatura.
The human immunodeficiency virus is the cause of the acquired immunodeficiency syndrome, a disease that represents one of the major public health problems worldwide. In spite of advances in antiretroviral therapy that increase patients' life expectancy, hematological changes, such as anemia, follow the clinical course of the disease. This commonly multifactorial condition can be found in any phase of the disease and directly affects the prognosis and quality of life of patients. This article presents information on the emergence of the anemic process based on the main causes found in the literature.
Asunto(s)
Humanos , Infecciones por VIH/complicaciones , Anemia/etiología , Recuento de Células Sanguíneas , Infecciones por VIH/fisiopatología , Infecciones por VIH/sangre , Síndrome de Inmunodeficiencia Adquirida/sangre , VIH/patogenicidad , Anemia/diagnóstico , Anemia/fisiopatologíaRESUMEN
BACKGROUND: People living with the Human Immunodeficiency Virus (PLHIV) have an increased susceptibility to develop non-communicable diseases such as cardiovascular disease (CVD). Infection with HIV contributes to the development of CVD independent of traditional risk factors, with endothelial dysfunction being the central physiological mechanism. While HIV-related mortality is declining due to antiretroviral treatment (ART), the number of deaths due to CVD is rising in South Africa - the country with the highest number of PLHIV and the world's largest ART programme. The EndoAfrica study was developed to determine whether HIV infection and ART are associated with cardiovascular risk markers and changes in vascular structure and function over 18 months in adults from different provinces of South Africa. This paper describes the rationale, methodology and baseline cohort profile of the EndoAfrica study conducted in the North West Province, South Africa. METHODS: In this case-control study, conducted between August 2017 and June 2018, 382 volunteers of African descent (276 women; 106 men), comprising of 278 HIV infected and 104 HIV free individuals were included. We measured health behaviours, a detailed cardiovascular profile, and performed biomarker analyses. We compared baseline characteristics, blood pressure, vascular function and biochemical markers between those infected and HIV free. RESULTS: At baseline, the HIV infected participants were older (43 vs 39 years), less were employed (21% vs 40%), less had a tertiary education (7% vs 16%) and their body mass index was lower (26 vs 29 kg/m2) than that of the HIV free participants. While the cardiovascular profile, flow-mediated dilation and pulse wave velocity did not differ, glycated haemoglobin was lower (p = 0.017) and total cholesterol, high density lipoprotein cholesterol, triglycerides, gamma-glutamyltransferase and tobacco use were higher (all p < 0.047) in PLHIV. CONCLUSION: Despite PLHIV being older, preliminary cross-sectional analysis suggests that PLHIV being treated with ART do not have poorer endothelial or vascular function compared to the HIV free participants. More detailed analyses on the baseline and follow-up data will provide further clarity regarding the cardiovascular profile of South Africans living with HIV.
Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/complicaciones , Síndrome de Inmunodeficiencia Adquirida/epidemiología , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/etiología , VIH , Síndrome de Inmunodeficiencia Adquirida/sangre , Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Adulto , Antirretrovirales/uso terapéutico , Biomarcadores/sangre , Presión Sanguínea , Estudios de Casos y Controles , HDL-Colesterol/sangre , Estudios Transversales , Femenino , Hemoglobina Glucada/análisis , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Enfermedades no Transmisibles , Análisis de la Onda del Pulso , Factores de Riesgo , Sudáfrica/epidemiología , Triglicéridos/sangreAsunto(s)
Síndrome de Inmunodeficiencia Adquirida , Linfohistiocitosis Hemofagocítica , Transfusión de Plaquetas/efectos adversos , Reacción a la Transfusión , Síndrome de Inmunodeficiencia Adquirida/sangre , Síndrome de Inmunodeficiencia Adquirida/patología , Síndrome de Inmunodeficiencia Adquirida/terapia , Adulto , Humanos , Linfohistiocitosis Hemofagocítica/sangre , Linfohistiocitosis Hemofagocítica/patología , Linfohistiocitosis Hemofagocítica/terapia , Masculino , Reacción a la Transfusión/sangre , Reacción a la Transfusión/terapiaRESUMEN
BACKGROUND: The goal of antiretroviral therapy (ART) is to suppress viral replication to undetectable levels. These low viral load (VL) levels may not be attained in some patients, a situation representing potential virological failure during the course of treatment. OBJECTIVES: To present the results of a Markov model exploring how virological failure and active tuberculosis (TB) affect the progression of HIV in patients on ART. METHODS: A continuous-time non-homogeneous Markov model was used to model the progression of HIV/AIDS in patients on combination ART (cART). We define seven states in our model. The first five states are based on VL levels and the other two are absorbing states: death and withdrawal from the study. The effects of TB co-infection, baseline VL, lactic acidosis and treatment failure on transition intensities were assessed. RESULTS: The model shows that VL-based transition intensities do not follow a constant rate; rather, there are two different trends in HIV/AIDS progression. The first trend is an increase in the prevalence of state 1 (undetectable VL levels) in the first 0.5 years of treatment. The second trend follows thereafter and shows a slow decrease. Within the first 0.5 years of therapeutic intervention, the undetectable VL state is therefore attainable from any VL state. However, when virological failure occurs, there is an increased risk of death. Developing active TB while on cART increases the risk of viral rebound from undetectable levels to VLs between 50 and 10 000 copies/mL by ~1.03-fold. From a VL between 10 000 and 100 000 copies/mL, developing TB while on cART increases the rate of viral rebound by ~2.5-fold. However, if TB is detected and treated at enrolment, rates of viral rebound from undetectable levels are reduced. CONCLUSIONS: The model confirms that virological failure, coupled with developing active TB while on cART, increases mortality rates irrespective of patient CD4+ count status. It also suggests that while TB at the time of cART initiation does not increase the risk of viral rebound, development of active TB after cART initiation does increase this risk. These findings highlight the importance of strengthening VL monitoring, which should be performed every 2 months, especially in patients with TB, and addressing unsuppressed VLs appropriately if they are detected.