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1.
Mem Inst Oswaldo Cruz ; 115: e200082, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32935750

RESUMO

Respiratory failure (RF) is the main cause of hospital admission in HIV/AIDS patients. This study assessed comorbidities and laboratory parameters in HIV/AIDS inpatients with RF (N = 58) in relation to those without RF (N = 36). Tuberculosis showed a huge relative risk and platelet counts were slightly higher in HIV/AIDS inpatients with RF. A flow cytometry assay for reactive oxygen species (ROS) showed lower levels in platelets of these patients in relation to the healthy subjects. However, when stimulated with adrenaline, ROS levels increased in platelets and platelet-derived microparticles of HIV/AIDS inpatients, which may increase the risk of RF during HIV and tuberculosis (HIV-TB) coinfection.


Assuntos
Micropartículas Derivadas de Células/metabolismo , Infecções por HIV/sangue , HIV/imunologia , Espécies Reativas de Oxigênio/sangue , Insuficiência Respiratória/complicações , Fármacos Anti-HIV/uso terapêutico , Biomarcadores/sangue , Plaquetas , Citometria de Fluxo , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Humanos , Insuficiência Respiratória/sangue
3.
Nature ; 585(7824): 261-267, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32848246

RESUMO

Sustained, drug-free control of HIV-1 replication is naturally achieved in less than 0.5% of infected individuals (here termed 'elite controllers'), despite the presence of a replication-competent viral reservoir1. Inducing such an ability to spontaneously maintain undetectable plasma viraemia is a major objective of HIV-1 cure research, but the characteristics of proviral reservoirs in elite controllers remain to be determined. Here, using next-generation sequencing of near-full-length single HIV-1 genomes and corresponding chromosomal integration sites, we show that the proviral reservoirs of elite controllers frequently consist of oligoclonal to near-monoclonal clusters of intact proviral sequences. In contrast to individuals treated with long-term antiretroviral therapy, intact proviral sequences from elite controllers were integrated at highly distinct sites in the human genome and were preferentially located in centromeric satellite DNA or in Krüppel-associated box domain-containing zinc finger genes on chromosome 19, both of which are associated with heterochromatin features. Moreover, the integration sites of intact proviral sequences from elite controllers showed an increased distance to transcriptional start sites and accessible chromatin of the host genome and were enriched in repressive chromatin marks. These data suggest that a distinct configuration of the proviral reservoir represents a structural correlate of natural viral control, and that the quality, rather than the quantity, of viral reservoirs can be an important distinguishing feature for a functional cure of HIV-1 infection. Moreover, in one elite controller, we were unable to detect intact proviral sequences despite analysing more than 1.5 billion peripheral blood mononuclear cells, which raises the possibility that a sterilizing cure of HIV-1 infection, which has previously been observed only following allogeneic haematopoietic stem cell transplantation2,3, may be feasible in rare instances.


Assuntos
Inativação Gênica , Infecções por HIV/genética , Infecções por HIV/virologia , HIV-1/genética , Heterocromatina/genética , Provírus/genética , Integração Viral/genética , Latência Viral/genética , Adulto , Idoso , Centrômero/genética , Cromossomos Humanos Par 19/genética , DNA Satélite/genética , Feminino , Genoma Viral/genética , Infecções por HIV/sangue , HIV-1/isolamento & purificação , Heterocromatina/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Provírus/isolamento & purificação , Proteínas Repressoras/genética , Sítio de Iniciação de Transcrição
4.
PLoS One ; 15(8): e0236510, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32790765

RESUMO

BACKGROUND: Poor vitamin D status is a global health problem and common in patients with human immunodeficiency virus (HIV) in high-income countries. There is less evidence on prevalence of vitamin D deficiency and nutrition and growth in HIV-infected and -exposed children in low- and middle-income countries. OBJECTIVES: To determine the vitamin D status in Batswana HIV-infected mothers and their children, differences among HIV-infected mothers and between HIV-exposed and -infected infants and children, and associations between vitamin D and disease-related outcomes, nutrition, and growth. METHODS: This was a cross-sectional study of HIV+ mothers and HIV-exposed infants and unrelated children (1-7.9 years). Serum 25-hydroxyvitamin D (25(OH)D) was measured, among other nutritional indicators, for mothers, infants and children. Vitamin D status for HIV-infected mothers and children, and an immune panel was assessed. History of HIV anti-retroviral medications and breastfeeding were obtained. Data were collected prior to universal combination antiretroviral therapy in pregnancy. RESULTS: Mothers (n = 36) had a mean serum 25(OH)D of 37.2±12.4ng/mL; 11% had insufficient (<20ng/mL), 17% moderately low (20.0-29.9ng/mL) and 72% sufficient (≥30ng/mL) concentrations. No infants (n = 36) or children (n = 48) were vitamin D insufficient; 22% of HIV- and no HIV+ infants had moderately low concentrations and 78% of HIV- and 100% of HIV+ infants had sufficient status, 8% of HIV- and no HIV+ children had moderately low concentrations and 92% of HIV- and 100% HIV+ children had sufficient concentrations. HIV+ children had significantly lower length/height Z scores compared to HIV- children. Length/height Z score was positively correlated with serum 25(OH)D in all children (r = 0.33, p = 0.023), with a stronger correlation in the HIV+ children (r = 0.47 p = 0.021). In mothers, serum 25(OH)D was positively associated with CD4% (r = 0.40, p = 0.016). CONCLUSIONS: Results showed a low prevalence of vitamin D insufficiency in Botswana. Growth was positively correlated with vitamin D status in HIV-exposed children, and HIV+ children had poorer linear growth than HIV- children.


Assuntos
Infecções por HIV/epidemiologia , Deficiência de Vitamina D/epidemiologia , Adulto , Botsuana/epidemiologia , Criança , Desenvolvimento Infantil , Saúde da Criança , Pré-Escolar , Estudos Transversais , Feminino , Infecções por HIV/sangue , Infecções por HIV/complicações , Humanos , Lactente , Mães , Estado Nutricional , Gravidez , Complicações Infecciosas na Gravidez/sangue , Complicações Infecciosas na Gravidez/epidemiologia , Efeitos Tardios da Exposição Pré-Natal/sangue , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Vitamina D/análogos & derivados , Vitamina D/sangue , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/complicações , Adulto Jovem
5.
BMC Infect Dis ; 20(1): 582, 2020 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-32762646

RESUMO

BACKGROUND: Limited data are available on the effect of antiretroviral treatment (ART) or Tenofovir disoproxil fumarate (TDF) on renal function in Ethiopians. We aimed to assess factors associated with renal function changes during the first year of ART with special focus on TDF. METHODS: HIV positive persons who were ≥ 18 years of age and eligible for ART initiation were recruited. Creatinine measurement to estimate glomerular filtration rate (eGFR) and spot urine analyses were performed at baseline and after 3, 6 and 12 months of ART. Univariate and multivariate linear regression and univariate logistic regression were used to determine factors associated with eGFR as continuous and categorical variable respectively. A linear mixed model was used to assess 12 month eGFR difference in TDF and non-TDF based regimen. RESULT: Of 340 ART-naïve HIV patients with baseline renal function tests, 82.3% (279/339) were initiated on a TDF based ART regimen. All patients were on non-nucleoside reverse transcriptase inhibitors (NNRTI) based ART regimen. The median (IQR) change in eGFR with 12 months of ART was 0.8 (- 11.1; 10.0) ml/min/1.73m2. About 41 and 26.9% of HIV patients had a drop of greater than 3 and 10 mL/min/1.73 m2 in eGFR at 12 month, respectively. However, none of the HIV patients declined to < 60 ml/min/1.73m2 within 12 months. Moreover, none of the HIV patients had persistent proteinuria or glycosuria. Older HIV patients especially age > 45 years and those with unsuppressed viral load at 6 month of ART had a significantly lower eGFR at 12 months of ART initiation. However, there was no difference in 12 month eGFR between HIV patients initiated on TDF based regimen and non-TDF based regimen. CONCLUSION: Renal function remained stable with no difference between HIV patients treated with TDF or non-TDF NNRTI based ART regimen over 12 months. However, older HIV patients and those with unsuppressed viral load deserve special focus on renal monitoring. Data on long-term safety of TDF (> 1 year) is still warranted in this population.


Assuntos
Fármacos Anti-HIV/efeitos adversos , Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Rim/efeitos dos fármacos , Tenofovir/efeitos adversos , Tenofovir/uso terapêutico , Adolescente , Adulto , Creatinina/sangue , Etiópia/epidemiologia , Feminino , Seguimentos , Taxa de Filtração Glomerular/efeitos dos fármacos , Infecções por HIV/sangue , Infecções por HIV/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Proteinúria , Fatores de Risco , Carga Viral , Adulto Jovem
6.
Medicine (Baltimore) ; 99(34): e21799, 2020 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-32846815

RESUMO

Hepatitis B (HBV) and hepatitis C (HCV) viruses are hepatotropic and lymphotropic viruses that can proliferate either in lymphocytes and monocytes or hepatocytes.The aim of this study was to evaluate the seroprevalence of HBV, HCV, and human immunodeficiency virus (HIV) in patients with plasma cell disorders. We also aimed to compare patients with plasma cell disorders and chronic lymphocytic leukemia (CLL) in terms of HBV, HCV, and HIV seropositivity.This is a retrospective study. The patients who had patient file in the Multiple Myeloma Outpatient Unit of our hospital and were followed in our outpatient unit between January 1, 2012 and September 15, 2019, with diagnoses of either of the plasma cell disorders were included in the study. In addition, 272 CLL patients who were admitted to the Leukemia Outpatient Unit of our hospital were also enrolled in the study. The 2 disease groups were compared in terms of HBV, HCV, and HIV seropositivity.A statistically significant relationship was found between disease groups according to hepatitis B surface antigen (P < .05). Hepatitis B positivity were found to be more common in CLL patients. There was also a statistically significant relationship between the disease groups in terms of hepatitis B e antigen positivity (P = .001).We found that hepatitis B surface antigen positivity rate in CLL patients was higher than in patients with plasma cell disorders. Seroprevalence of HBV, HCV, and HIV was found to be very low in patients with plasma cell disorders.


Assuntos
Soroprevalência de HIV , Antígenos da Hepatite B/sangue , Hepatite B/epidemiologia , Hepatite C/epidemiologia , Leucemia Linfocítica Crônica de Células B/epidemiologia , Paraproteinemias/epidemiologia , Idoso , Comorbidade , Feminino , Infecções por HIV/sangue , Infecções por HIV/imunologia , Hepatite B/sangue , Antígenos da Hepatite B/imunologia , Antígenos do Núcleo do Vírus da Hepatite B/sangue , Antígenos do Núcleo do Vírus da Hepatite B/imunologia , Antígenos de Superfície da Hepatite B/sangue , Antígenos de Superfície da Hepatite B/imunologia , Antígenos E da Hepatite B/sangue , Anticorpos Anti-Hepatite C/sangue , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/epidemiologia , Plasmócitos/patologia , Estudos Retrospectivos , Estudos Soroepidemiológicos
7.
PLoS One ; 15(8): e0237580, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32790740

RESUMO

BACKGROUND: HIV screening (i.e. antigen/antibody) tests are followed by a supplemental (i.e. antibody-only) if the screen is positive. Discrepant results can result from two scenarios: a false-positive screening test or acute HIV infection. These scenarios can be distinguished by a molecular HIV test, but due to contamination concerns, our laboratory recently implemented a policy requiring a second specimen dedicated for molecular HIV testing. Our objective was to (1) characterize the effect of this policy on the time-to-diagnosis for patients with discrepant screening and supplemental test results, and (2) explore "strength of positivity" as an interim predictor of screening test accuracy while awaiting confirmatory test results. METHODS: Data from our laboratory information system, electronic health record, and instrument logs were used to collate data for all HIV testing performed at Barnes-Jewish Hospital (BJH) between January 1, 2014 and October 18, 2017. RESULTS: Requiring a dedicated specimen for molecular testing significantly increased the time-to-diagnosis for patients with discrepant screening and supplemental HIV tests (p = 0.0084). This policy also contributed to loss-to-followup, with 0/35 discrepant cases lost-to-followup prior to policy implementation compared to 2/10 after implementation. However, by optimizing the signal-to-cutoff (S/CO) ratio of the screening test, we were able to more accurately distinguish false-positives from acute-HIV prior to molecular testing (sensitivity of 100%, specificity of 89%). CONCLUSIONS: We propose utilizing quantitative fourth-generation assay results (S/CO) ratios as a predictor of infection true positivity in situations where the screening assay is reactive but the supplemental test is negative and confirmatory molecular results are not immediately available.


Assuntos
Sorodiagnóstico da AIDS/normas , Anticorpos Anti-HIV/sangue , Antígenos HIV/imunologia , Infecções por HIV/diagnóstico , Infecções por HIV/prevenção & controle , HIV-1/imunologia , Programas de Rastreamento/métodos , Algoritmos , Reações Falso-Positivas , Anticorpos Anti-HIV/imunologia , Infecções por HIV/sangue , Infecções por HIV/virologia , Humanos
8.
PLoS One ; 15(8): e0237739, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32817629

RESUMO

OBJECTIVE: To assess the effect of HIV infection and combined antiretroviral therapy (c-ART) on various proatherogenic biomarkers and lipids and to investigate their relationship with subclinical atherosclerosis in a cohort of treatment-naive HIV-infected patients. METHODS: We performed a prospective, comparative, multicenter study of 2 groups of treatment-naive HIV-infected patients (group A, CD4>500 cells/µL, not starting c-ART; and group B, CD4<500 cells/µL, starting c-ART at baseline) and a healthy control group. Laboratory analyses and carotid ultrasound were performed at baseline and at months 12 and 24. The parameters measured were low-density lipoprotein (LDL) particle phenotype, lipoprotein-associated phospholipase A2 (Lp-PLA2), interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), sCD14, sCD163, monocyte chemoattractant protein-1(MCP-1), and asymmetric dimethylarginine (ADMA). A linear mixed model based on patient clusters was used to assess differences in biomarkers between the study groups and over time. RESULTS: The study population comprised 62 HIV-infected patients (group A, n = 31; group B, n = 31) and 22 controls. Age was 37 (30-43) years, and 81% were men. At baseline, the HIV-infected patients had a worse LDL particle phenotype and higher plasma concentration of sCD14, sCD163, hs-CRP, and LDL-Lp-PLA2 than the controls. At month 12, there was an increase in total cholesterol (p = 0.002), HDL-c (p = 0.003), and Apo A-I (p = 0.049) and a decrease in sCD14 (p = <0.001) and sCD163 (p<0.001), although only in group B. LDL particle size increased in group B at month 24 (p = 0.038). No changes were observed in group A or in the healthy controls. Common carotid intima-media thickness increased in HIV-infected patients at month 24 (Group A p = 0.053; group B p = 0.048). Plasma levels of sCD14, sCD163, and hs-CRP correlated with lipid values. CONCLUSIONS: In treatment-naive HIV-infected patients, initiation of c-ART was associated with an improvement in LDL particle phenotype and inflammatory/immune biomarkers, reaching values similar to those of the controls. HIV infection was associated with progression of carotid intima-media thickness.


Assuntos
Aterosclerose/sangue , Biomarcadores/sangue , Infecções por HIV/sangue , Lipídeos/sangue , Adulto , Antirretrovirais/administração & dosagem , Antirretrovirais/sangue , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Aterosclerose/tratamento farmacológico , Aterosclerose/virologia , Proteína C-Reativa/metabolismo , Espessura Intima-Media Carotídea , Colesterol/sangue , Grupos Controle , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Humanos , Inflamação/sangue , Inflamação/tratamento farmacológico , Inflamação/virologia , Lipoproteínas LDL/sangue , Masculino , Estudos Prospectivos
9.
PLoS One ; 15(8): e0237633, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32845933

RESUMO

BACKGROUND: Indeterminate HIV test results are common, but little is known about the evolution of indeterminate serology and its sociodemographic and behavioral correlates. We assessed future HIV serological outcomes for individuals with indeterminate results and associated factors in Rakai, Uganda. METHODS: 115,944 serological results, defined by two enzyme immunoassay (EIAs), among 39,440 individuals aged 15-49 years in the Rakai Community Cohort Study were assessed. Indeterminate results were defined as contradictory EIAs. Modified Poisson regression models with generalized estimating equations were used to assess prevalence ratios (PRs) of subsequent HIV serological outcomes and factors associated with HIV indeterminate results. RESULTS: The prevalence of HIV serologically indeterminate results was 4.9%. Indeterminate results were less likely among women than men (adjPR 0.76, 95% CI 0.71,0.81), in unmarried participants than married participants (adjPR 0.92, 95% CI 0.85,99), and in individuals with primary (adjPR 0.90, 95% CI 0.80,1.02), secondary (adjPR 0.83, 95% CI 0.73,0.96) and post-secondary (adjPR 0.75, 95% CI 0.60,0.94) education, relative to no education. The proportions of persons with indeterminate results progressing to HIV positive, negative or indeterminate results in subsequent visits was 5%, 71% and 24%, respectively. CONCLUSION: HIV serologically indeterminate results were associated with gender and marital status. HIV surveillance programs should develop a protocol for reporting individuals with mixed or persistently indeterminate HIV results on multiple follow-up visits. Most indeterminate results became HIV-negative over time, but follow-up is still needed to detect positive serologies.


Assuntos
Sorodiagnóstico da AIDS/normas , Infecções por HIV/diagnóstico , HIV/isolamento & purificação , Adolescente , Adulto , Feminino , Seguimentos , Infecções por HIV/sangue , Infecções por HIV/epidemiologia , Humanos , Estudos Longitudinais , Masculino , Casamento , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Uganda/epidemiologia , Adulto Jovem
10.
S Afr Med J ; 110(4): 313-319, 2020 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-32657744

RESUMO

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.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Antituberculosos/uso terapêutico , Coinfecção , Infecções por HIV/tratamento farmacológico , Tuberculose/tratamento farmacológico , Acidose Láctica/induzido quimicamente , Síndrome de Imunodeficiência Adquirida/sangue , Síndrome de Imunodeficiência Adquirida/complicações , Síndrome de Imunodeficiência Adquirida/tratamento farmacológico , Adolescente , Adulto , Idoso , Contagem de Linfócito CD4 , Progressão da Doença , Interações Medicamentosas , Farmacorresistência Viral , Feminino , Infecções por HIV/sangue , Infecções por HIV/complicações , Humanos , Tuberculose Latente/complicações , Masculino , Cadeias de Markov , Adesão à Medicação , Pessoa de Meia-Idade , Mortalidade , Doenças do Sistema Nervoso Periférico/induzido quimicamente , População Rural , África do Sul , Resposta Viral Sustentada , Falha de Tratamento , Tuberculose/complicações , Carga Viral , Adulto Jovem
11.
Proc Natl Acad Sci U S A ; 117(31): 18692-18700, 2020 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-32690683

RESUMO

A scalable approach for quantifying intact HIV-1 proviruses is critical for basic research and clinical trials directed at HIV-1 cure. The intact proviral DNA assay (IPDA) is a novel approach to characterizing the HIV-1 reservoir, focusing on the genetic integrity of individual proviruses independent of transcriptional status. It uses multiplex digital droplet PCR to distinguish and separately quantify intact proviruses, defined by a lack of overt fatal defects such as large deletions and APOBEC3G-mediated hypermutation, from the majority of proviruses that have such defects. This distinction is important because only intact proviruses cause viral rebound on ART interruption. To evaluate IPDA performance and provide benchmark data to support its implementation, we analyzed peripheral blood samples from 400 HIV-1+ adults on ART from several diverse cohorts, representing a robust sample of treated HIV-1 infection in the United States. We provide direct quantitative evidence that defective proviruses greatly outnumber intact proviruses (by >12.5 fold). However, intact proviruses are present at substantially higher frequencies (median, 54/106 CD4+ T cells) than proviruses detected by the quantitative viral outgrowth assay, which requires induction and in vitro growth (∼1/106 CD4+ T cells). IPDA amplicon signal issues resulting from sequence polymorphisms were observed in only 6.3% of individuals and were readily apparent and easily distinguished from low proviral frequency, an advantage of the IPDA over standard PCR assays which generate false-negative results in such situations. The large IPDA dataset provided here gives the clearest quantitative picture to date of HIV-1 proviral persistence on ART.


Assuntos
DNA Viral/sangue , Infecções por HIV , Provírus/genética , Latência Viral/genética , Adulto , Feminino , Infecções por HIV/sangue , Infecções por HIV/epidemiologia , Infecções por HIV/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase/métodos
12.
PLoS One ; 15(7): e0235865, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32634155

RESUMO

HIV-associated/epidemic Kaposi's sarcoma (EpKS) is an AIDS-defining angio-proliferative malignancy. It can be treated with antiretroviral therapy (ART) alone or with ART plus cytotoxic chemotherapy. ART-treated EpKS can either respond or worsen upon treatment. This study aimed at identifying immunological markers of ART-treatment response. We compared responders (those with clinical EpKS tumor regression) versus poor responders (those with progressive or non-responsive EpKS). We measured plasma cytokine and chemokine levels using cytometric bead assays. Kaposi's sarcoma herpesvirus (KSHV) neutralizing antibody (nAb) responses were also quantified to test associations with treatment outcome. Interleukin (IL)-5 levels were significantly elevated in responders versus poor-responders at baseline (0.76pg/ml vs. 0.37pg/ml; p<0.01) and follow-up (0.56pg/ml vs. 0.37pg/ml; p<0.01); IL-6 was lower in responders than poor-responders at follow-up (600fg/ml vs. 4272fg/ml; p<0.05). IP-10/CxCL-10 was significantly lower at follow-up in responders versus poor-responders (187pg/ml vs. 528pg/ml; p<0.01). KSHV nAb were not significantly differential between responders and poor-responders. In conclusion, high plasma IL-5 at baseline could be a marker for ART-treated KS tumor regression, whereas increased pro-inflammatory cytokine IL-6, and the chemokine IP-10, associate with KS tumor progression.


Assuntos
Biomarcadores Tumorais/sangue , Citocinas/sangue , Infecções por HIV/tratamento farmacológico , Sarcoma de Kaposi/tratamento farmacológico , Adulto , Antirretrovirais/uso terapêutico , Feminino , Infecções por HIV/sangue , Infecções por HIV/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Sarcoma de Kaposi/sangue , Sarcoma de Kaposi/complicações , Resultado do Tratamento , Carga Viral
13.
West Afr J Med ; 37(3): 260-267, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32476120

RESUMO

BACKGROUND: HIV has direct and indirect effects on the liver, just as hepatitis B and C viral infections are both hepatotropic viruses. Co-infection is an emerging clinical problem among HIV infected individuals, therefore its prevalence and impact on hepatic functions in children requires evaluation. METHODS: A cross sectional hospital-based study was conducted among HIV infected children and adolescents aged 2 months to 18 years on antiretroviral therapy at the University of Abuja Teaching Hospital from October 2017 to March 2018. Determination of hepatitis B surface antigen, antibody to hepatitis C, liver function tests and liver sizes were carried out on the children. RESULTS: Of a total of 153 subjects recruited, 89(58.2%) were males, 69 (45.1%) were adolescents and 117(76.5%) from lower socio-economic class. Hundred and forty (91.5%) subjects were mono-infected, 7(4.6%) had co-infection with HBsAg, 1(0.7%) had HBsAg/HBeAg, 6(3.9%) had HCV, while none had triple infection. No under-five had co-infection with HBV and no variable had significant association with HBV coinfection. There was however significant association of HCV co-infection with age (p=0.00), blood transfusion (p=0.03), and religion (p=0.01) and all the infected were less than 10 years. The mean values for alanine transaminase, aspartate transaminase, alkaline phosphatase, liver sizes of the mono and co-infected were all within normal and none had severe or life threatening hepatotoxicity. CONCLUSION: The prevalence and impact of HIV co-infection on liver function in this study was low. Use of liver biopsy, the gold standard for assessing disease severity in liver conditions may also be required for in-depth assessment.


Assuntos
Terapia Antirretroviral de Alta Atividade , Coinfecção/epidemiologia , Infecções por HIV/tratamento farmacológico , Hepatite B/complicações , Hepatite C/complicações , Adolescente , Alanina Transaminase/sangue , Criança , Pré-Escolar , Estudos Transversais , Feminino , Infecções por HIV/sangue , Infecções por HIV/epidemiologia , Hepacivirus/isolamento & purificação , Hepatite B/sangue , Hepatite B/epidemiologia , Antígenos de Superfície da Hepatite B , Vírus da Hepatite B/isolamento & purificação , Hepatite C/sangue , Hepatite C/epidemiologia , Humanos , Lactente , Testes de Função Hepática , Masculino , Nigéria/epidemiologia , Prevalência
14.
Medicine (Baltimore) ; 99(21): e19978, 2020 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-32481261

RESUMO

Sub-Saharan Africa has the vast majority (∼90%) of new pediatric acquired immunodeficiency syndrome cases worldwide. Biologically monitoring HIV-infected pediatric populations remains challenging. The differential interest of human immunodeficiency virus (HIV)-1 RNA loads and CD4 T-cell counts is debated for the treatment of pediatric acquired immunodeficiency syndrome patients.Long-term antiretroviral treatment (ART) outcomes regarding immunological and virological surrogate markers were longitudinally evaluated between 2009 and 2014 (over 57 months) in 245 perinatally HIV-1-infected children and adolescents born from HIV-infected mothers, treated at inclusion for at least 6 months by the World Health Organization-recommended ART in Bangui, Central African Republic.Patients were monitored over time biologically for CD4 T-cell counts, HIV-1 RNA loads, and drug resistance mutation genotyping.Children lost to follow-up totaled 6%. Four categories of immunovirological responses to ART were observed. At baseline, therapeutic success with sustained immunological and virological responses was observed in 80 (32.6%) children; immunological and virologic nonresponses occurred in 32 (13.0%) children; finally, the majority (133; 54.2%) of the remaining children showed discordant immunovirological responses. Among them, 33 (13.4%) children showed rapid virological responses to ART with an undetectable viral load, whereas immunological responses remained absent after 6 months of treatment and increased progressively over time in most of the cases, suggesting slow immunorestoration. Notably, nearly half of the children (40.8% at baseline and 48.2% at follow-up) harbored discordant immunovirological responses with a paradoxically high CD4 T-cell count and HIV-1 RNA load, which are always associated with high levels of drug resistance mutations. The latter category showed a significant increase over time, with a growth rate of 1.23% per year of follow-up.Our STROBE-compliant study demonstrates the high heterogeneity of biological responses under ART in children with frequent passage from 1 category to another over time. Close biological evaluation with access to routine plasma HIV-1 RNA load monitoring is crucial for adapting the complex outcomes of ART in HIV-infected children born from infected mothers.


Assuntos
Antirretrovirais/uso terapêutico , Infecções por HIV/sangue , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , HIV-1/genética , RNA Viral/sangue , Adolescente , Contagem de Linfócito CD4 , República Centro-Africana , Criança , Pré-Escolar , Feminino , Seguimentos , Infecções por HIV/transmissão , Humanos , Lactente , Transmissão Vertical de Doença Infecciosa , Masculino , Gravidez , Complicações Infecciosas na Gravidez/tratamento farmacológico , Estudos Prospectivos
15.
Ann Parasitol ; 66(2): 135-141, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32530590

RESUMO

There is an increasing concern about the co-infection of visceral leishmaniosis (VL) with human immunodeficiency virus (HIV) and/or viral hepatitis B/C. The aim of this study was to determine the prevalence of HIV and viral hepatitis co-infections among VL patients in a hyperendemic area in Eastern Sudan and to assess antibody levels in co-infected patients. This is a retrospective study where the sera of confirmed VL cases and non-VL individuals were analysed. The sera were screened for co-infections using immunochromatographic tests and ELISA for anti-HIV 1+2 antibodies, hepatitis B surface antigen (HBsAg), and anti-hepatitis C virus (HCV). Anti-Leishmania donovani antibodies in the sera of VL alone were assessed and compared to the sera of co-infected patients. Of the 100 screened VL sera, 6 (6%), 0 (0%), and 1 (1%) were positive for HBsAg, anti-HCV, and anti-HIV, respectively. These values were 5 (5%), 0 (0%), and 1 (1%) in the control group. Of note, the HCV screening test (Biorex, UK) showed positive reactivity in 32 (32%) and 17 (17%) sera of VL and control groups, respectively. All reactive sera tested negative in HCV ELISA. Of the 93 VL sera, 75 (80.6%) had strong DAT titers (1:˃102400), 2 (2.1%) demonstrated the lowest DAT titers (1:≤800), and 5 (5.4%) had marginal DAT titers (1:1600). Interestingly, the VL/HIV co-infected serum had a negative antibody titer (1:1600). Of the 6 VL/HBV co-infected sera, 1 (16.7%) and 5 (83.3%) demonstrated moderate (1:12800­1:51600) and strong (1:≥102400) DAT titers, respectively. The strong DAT titers observed in the VL/HBV co-infected sera were comparable to the DAT titers of the VL sera. The VL co-infection with HIV and hepatitis B/C is low in endemic areas in Eastern Sudan but may create a diagnostic difficulty. VL/HIV co-infected patients can have low Leishmania antibodies, thus alternative methodologies (e.g., antigen tests) may help the diagnosis.


Assuntos
Infecções por HIV , Hepatite Viral Humana , Leishmaniose Visceral , Anticorpos/sangue , Infecções por HIV/sangue , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Hepatite Viral Humana/sangue , Hepatite Viral Humana/complicações , Hepatite Viral Humana/epidemiologia , Humanos , Leishmaniose Visceral/complicações , Leishmaniose Visceral/epidemiologia , Prevalência , Estudos Retrospectivos , Estudos Soroepidemiológicos , Sudão/epidemiologia
16.
Int J Infect Dis ; 97: 347-351, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32526391

RESUMO

OBJECTIVE: To describe the clinical and epidemiological profiles of HIV-infected Omani children before and after the implementation of the prevention of mother-to-child transmission of HIV (PMTCT) programme. METHODS: A retrospective review of HIV-infected children seen at a national paediatric HIV unit between 1992 and 2015 was performed. RESULTS: Ninety-one HIV-infected children were identified; 59 (65%) were ≤5 years of age at diagnosis, with 28 (47.5%) of these being <1 year old. The average annual incidence of infection per million children (≤14 years old) was 5.7, and the highest (11.6) was in 2010. At diagnosis, 48 (60%) patients had a CD4 count of ˂200cells/mm3. The median HIV viral load was 81600copies/ml at diagnosis and 5911copies/ml at 12 months after HIV treatment (p=0.015). The median CD4 count was 586cells/mm3 at diagnosis and 800cells/mm3 at 12 months after therapy (p=0.004). Compared to those diagnosed before 2009 (n=68), HIV-infected children diagnosed after 2009 (n=22) were more likely to be asymptomatic at the time of HIV diagnosis (23.5% (16/68) vs. 59.1% (13/22); p=0.002) and to have a favourable clinical outcome (42.6% (29/68) vs. 86.4% (19/22); p<0001). CONCLUSIONS: The number of HIV-infected children in Oman has decreased substantially since the introduction of the PMTCT programme. Furthermore, the HIV-infected children diagnosed after 2009 had higher proportions of asymptomatic HIV infections at diagnosis and favourable clinical outcomes, in comparison to those diagnosed before 2009.


Assuntos
Infecções por HIV/epidemiologia , Adolescente , Adulto , Contagem de Linfócito CD4 , Criança , Pré-Escolar , Feminino , Infecções por HIV/sangue , Infecções por HIV/transmissão , Humanos , Lactente , Transmissão Vertical de Doença Infecciosa/estatística & dados numéricos , Masculino , Omã/epidemiologia , Estudos Retrospectivos , Adulto Jovem
17.
Int J Infect Dis ; 97: 365-370, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32553717

RESUMO

OBJECTIVES: The aim was to fully characterize the plasma and urine washout pharmacokinetics of tenofovir (TFV) in adults following 6 weeks of controlled levels of tenofovir disoproxil fumarate (TDF) adherence, in order to inform the utility of clinic-based adherence testing. DESIGN: This was a three-arm, randomized, open-label study in adult volunteers. Participants were randomized to receive TDF 300 mg/emtricitabine (FTC) 200 mg as (1) 7 doses/week (perfect adherence), (2) 4 doses/week (moderate adherence), or (3) 2 doses/week (low adherence). Plasma and urine samples were collected regularly during the 6-week dosing phase and for 4 weeks following drug cessation. RESULTS: Twenty-eight adults were included in this analysis. Median (range) age was 33 (20-49) years. No differences in TFV pharmacokinetic parameters during the washout were observed across the study arms. Small differences in TFV plasma concentrations occurred across arms between 4 and 10 h post-dose. The cumulative amount of TFV excreted in urine was not different at 24 h post-dose, but at 148 h it was 24.8 mg, 21.0 mg, and 17.2 mg for the perfect, moderate, and low adherence arms, respectively (p = 0.043). CONCLUSIONS: Among adults with different TDF adherence patterns, relative differences in plasma concentrations and cumulative urine extraction of TFV were minor following cessation. TFV measurement in plasma or urine is more indicative of last drug ingestion, rather than prior dose patterns.


Assuntos
Infecções por HIV/tratamento farmacológico , Infecções por HIV/psicologia , Tenofovir/farmacocinética , Adulto , Fármacos Anti-HIV/sangue , Fármacos Anti-HIV/farmacocinética , Fármacos Anti-HIV/uso terapêutico , Fármacos Anti-HIV/urina , Emtricitabina/administração & dosagem , Emtricitabina/sangue , Emtricitabina/farmacocinética , Feminino , Infecções por HIV/sangue , Infecções por HIV/urina , Comportamentos Relacionados com a Saúde , Humanos , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Plasma/química , Tenofovir/sangue , Tenofovir/uso terapêutico , Tenofovir/urina , Adulto Jovem
18.
PLoS One ; 15(6): e0235162, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32584913

RESUMO

BACKGROUND: Preterm birth is the leading cause of neonatal and child mortality worldwide. Maternal HIV infection and antiretroviral treatment (ART) increase the rate of preterm birth, but the underlying mechanisms remain unknown, limiting progress in prediction, prevention and treatment. While overall γδ T cell levels remain constant, acute HIV infection is associated with a depletion of the Vδ2 subset and an increase in the Vδ1 subset, which do not return to baseline with ART. γδ T cells have also been implicated in adverse pregnancy outcomes and we therefore investigated the potential association between maternal HIV infection, peripheral γδ T cell frequencies and preterm birth. METHODS: Study participants were HIV positive (n = 47) and HIV negative (n = 45) women enrolled in a prospective pregnancy cohort study at Chris Hani Baragwanath Academic Hospital in Soweto, South Africa. Women were enrolled in early pregnancy and gestational age was accurately determined by first trimester ultrasound scan. Peripheral blood samples were collected in each trimester and peripheral blood mononuclear cells isolated. Frequencies of γδ T cells, Vδ1+ and Vδ2+ γδ T cell subsets, and CCR6 chemokine receptor expression were determined by flow cytometry. RESULTS: Total γδ T cell levels were similar between HIV positive and HIV negative women throughout pregnancy. However, in each trimester maternal HIV infection was associated with reduced levels of the Vδ2+ subset and increased levels of the Vδ1+ subset, leading to a reversal of the Vδ1/Vδ2 ratio. Timing of ART initiation among HIV positive women did not affect levels of γδ T cells, the Vδ1+ and Vδ2+ subsets, or the Vδ1/Vδ2 ratio. Importantly, preterm birth was associated with lower total γδ T cell levels in early pregnancy and γδ T cell frequencies were lowest in HIV positive women who delivered preterm. Moreover, in the first trimester the proportion of Vδ1+ T cells that were CCR6+ was significantly reduced in HIV+ women and women who delivered preterm, resulting in the lowest proportion of CCR6+ Vδ1 T cells in HIV positive women who delivered preterm. CONCLUSIONS: Our findings suggest that altered γδ T cell frequencies may link maternal HIV infection and preterm birth. γδ T cell frequencies in early pregnancy may serve as predictive biomarkers to identify women at risk of delivering preterm.


Assuntos
Infecções por HIV/sangue , HIV-1 , Nascimento Prematuro/sangue , Receptores de Antígenos de Linfócitos T gama-delta/sangue , Linfócitos T/metabolismo , Adulto , Biomarcadores/sangue , Feminino , Citometria de Fluxo , Infecções por HIV/tratamento farmacológico , Humanos , Imunossupressão , Gravidez , Complicações Infecciosas na Gravidez , Receptores CCR6/sangue , África do Sul
19.
Medicine (Baltimore) ; 99(20): e20065, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32443313

RESUMO

Despite viral control, basal chronic inflammation and its related comorbidities remain unsolved problems among HIV-infected individuals. Soluble factors derived from myeloid cells have emerged as potent markers associated with HIV-related comorbidities and mortality. In the present report, we explored the relationship between soluble programmed death-ligand 1 (sPD-L1) and HIV-1 infection, antiretroviral therapy (ART), CD4/CD8 ratio, viral load (VL), and sexually transmitted coinfections.A prospective observational study on 49 HIV-1 infected adults.We found sPD-L1 levels were significantly higher in 49 HIV infected subjects than in 30 uninfected adults (1.05 ng/ml vs 0.52 ng/ml; P < .001). In this line, sPD-L1 levels were found to be elevated in 16 HIV infected subjects with undetectable VL compared with the uninfected subjects (0.75 ng/ml vs 0.52 ng/ml; P = .02). Thirteen ART-treated individuals with virological failure exhibited the highest sPDL1 levels, which were significantly higher than both 20 ART naïve infected individuals (1.68 ng/ml vs 0.87 ng/ml; P = .003) and the 16 ART-treated individuals with suppressed viremia (1.68 ng/ml vs 0.79 ng/ml; P = 002). Entire cohort data showed a statistically significant positive correlation between VL and sPD-L1 levels in plasma (r = 0.3; P = 036).Our findings reveal sPDL-1 as a potential biomarker for HIV infection especially interesting in those individuals with virological failure.


Assuntos
Antígeno B7-H1/sangue , Infecções por HIV/sangue , Infecções por HIV/imunologia , HIV-1 , Adulto , Fármacos Anti-HIV/uso terapêutico , Biomarcadores/sangue , Feminino , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Carga Viral/efeitos dos fármacos , Carga Viral/imunologia
20.
PLoS One ; 15(4): e0232018, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32352972

RESUMO

INTRODUCTION: In many African countries, laboratory reference values are not established for the local healthy adult population. In Mozambique, reference values are known for young adults (18-24yo) but not yet established for a wider age range. Our study aimed to establish hematological, biochemical and immunological reference values for vaccine trials in Mozambican healthy adults with high-risk for HIV acquisition. METHODS: A longitudinal cohort and site development study in Mozambique between November 2013 and 2014 enrolled 505 participants between 18 to 35 years old. Samples from these healthy participants, were analyzed to determine reference values. All volunteers included in the analysis were clinically healthy and human immunodeficiency virus (HIV), hepatitis B and C virus, and syphilis negative. Median and reference ranges were calculated for the hematological, biochemical and immunological parameters. Ranges were compared with other African countries, the USA and the US National Institute of Health (NIH) Division of AIDS (DAIDS) toxicity tables. RESULTS: A total of 505 participant samples were analyzed. Of these, 419 participants were HIV, hepatitis B and C virus and syphilis negative including 203 (48.5%) females and 216 (51.5%) males, with a mean age of 21 years. In the hematological parameters, we found significant differences between sex for erythrocytes, hemoglobin, hematocrit, MCV, MCH and MCHC as well as white blood cells, neutrophils and platelets: males had higher values than females. There were also significant differences in CD4+T cell values, 803 cells/µL in men versus 926 cells/µL in women. In biochemical parameters, men presented higher values than women for the metabolic, enzymatic and renal parameters: total and direct bilirubin, ALT and creatinine. CONCLUSION: This study has established reference values for healthy adults with high-risk for HIV acquisition in Mozambique. These data are helpful in the context of future clinical research and patient care and treatment for the general adult population in the Mozambique and underline the importance of region-specific clinical reference ranges.


Assuntos
Células Sanguíneas/química , Infecções por HIV/prevenção & controle , Testes Hematológicos/normas , Adulto , Plaquetas/química , Estudos de Coortes , Feminino , Infecções por HIV/sangue , Hematócrito/normas , Hemoglobinas/análise , Humanos , Contagem de Leucócitos/normas , Leucócitos/química , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Moçambique/epidemiologia , Valores de Referência , Fatores de Risco
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