RESUMO
INTRODUCTION: The human immunodeficiency virus (HIV) and tuberculosis (TB) co-infection presents significant challenges due to the complex interplay between these diseases, leading to exacerbated metabolic disturbances. Understanding these metabolic profiles is crucial for improving diagnostic and therapeutic approaches. OBJECTIVE: This study aimed to characterise the urinary acylcarnitine and amino acid profiles, including 5-hydroxyindoleacetic acid (5-HIAA), in patients co-infected with HIV and TB using targeted liquid chromatography mass spectrometry (LC-MS) metabolomics. METHODS: Urine samples, categorised into HIV, TB, HIV/TB co-infected, and healthy controls, were analysed using HPLC-MS/MS. Statistical analyses included one-way ANOVA and a Kruskal-Wallis test to determine significant differences in the acylcarnitine and amino acid profiles between groups. RESULTS: The study revealed significant metabolic alterations, especially in TB and co-infected groups. Elevated levels of medium-chain acylcarnitines indicated increased fatty acid oxidation, commonly associated with cachexia in TB. Altered amino acid profiles suggested disruptions in protein and glucose metabolism, indicating a shift towards diabetes-like metabolic states. Notably, TB was identified as a primary driver of these changes, affecting protein turnover, and impacting energy metabolism in co-infected patients. CONCLUSION: The metabolic profiling of HIV/TB co-infection highlights the profound impact of TB on metabolic pathways, which may exacerbate the clinical complexities of co-infection. Understanding these metabolic disruptions can guide the development of targeted treatments and improve management strategies, ultimately enhancing the clinical outcomes for these patients. Further research is required to validate these findings and explore their implications in larger, diverse populations.
Assuntos
Aminoácidos , Carnitina , Coinfecção , Infecções por HIV , Metabolômica , Tuberculose , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Aminoácidos/urina , Aminoácidos/metabolismo , Carnitina/análogos & derivados , Carnitina/urina , Carnitina/metabolismo , Cromatografia Líquida de Alta Pressão/métodos , Coinfecção/urina , Coinfecção/metabolismo , Infecções por HIV/complicações , Infecções por HIV/urina , Infecções por HIV/metabolismo , Espectrometria de Massa com Cromatografia Líquida/métodos , Metabolômica/métodos , Espectrometria de Massas em Tandem/métodos , Tuberculose/urina , Tuberculose/metabolismoAssuntos
Fármacos Anti-HIV , Infecções por HIV , Adesão à Medicação , Profilaxia Pré-Exposição , Humanos , Infecções por HIV/prevenção & controle , Infecções por HIV/urina , Profilaxia Pré-Exposição/métodos , Profilaxia Pré-Exposição/economia , Fármacos Anti-HIV/uso terapêutico , Sistemas Automatizados de Assistência Junto ao Leito , Testes Imediatos/economia , Masculino , Urinálise/métodos , Urinálise/economiaRESUMO
INTRODUCTION: Amid the global health crisis, HIV/TB co-infection presents significant challenges, amplifying the burden on patients and healthcare systems alike. Metabolomics offers an innovative window into the metabolic disruptions caused by co-infection, potentially improving diagnosis and treatment monitoring. AIM: This study uses untargeted metabolomics to investigate the urinary metabolic signature of HIV/TB co-infection, enhancing understanding of the metabolic interplay between these infections. METHODS: Urine samples from South African adults, categorised into four groups - healthy controls, TB-positive, HIV-positive, and HIV/TB co-infected - were analysed using GCxGC-TOFMS. Metabolites showing significant differences among groups were identified through Kruskal-Wallis and Wilcoxon rank sum tests. RESULTS: Various metabolites (n = 23) were modulated across the spectrum of health and disease states represented in the cohorts. The metabolomic profiles reflect a pronounced disruption in biochemical pathways involved in energy production, amino acid metabolism, gut microbiome, and the immune response, suggesting a bidirectional exacerbation between HIV and TB. While both diseases independently perturb the host's metabolism, their co-infection leads to a unique metabolic phenotype, indicative of an intricate interplay rather than a simple additive effect. CONCLUSION: Metabolic profiling revealed a unique metabolic landscape shaped by HIV/TB co-infection. The findings highlight the potential of urinary differential metabolites for co-infection, offering a non-invasive tool for enhancing diagnostic precision and tailoring therapeutic interventions. Future research should focus on expanding sample sizes and integrating longitudinal analyses to build upon these foundational insights, paving the way for metabolomic applications in combating these concurrent pandemics.
Assuntos
Coinfecção , Infecções por HIV , Metabolômica , Tuberculose , Humanos , Infecções por HIV/complicações , Infecções por HIV/metabolismo , Infecções por HIV/urina , Metabolômica/métodos , Coinfecção/metabolismo , Adulto , Masculino , Tuberculose/metabolismo , Tuberculose/urina , Feminino , Pessoa de Meia-Idade , Metaboloma , Biomarcadores/urinaRESUMO
BACKGROUND: A retrospective study was conducted to explore the urinary expression of α 1-microglobulin (α1MG) and ß2-microglobulin (ß2MG) in patients with human immunodeficiency virus (HIV) infection, aiming to evaluate their predictive capability for renal injury. METHOD: One hundred and five male HIV-infected patients treated with Tenofovir (TDF) regimen (TDF+3TC or the third drug TDF/FTC+) were selected between March 1, 2021, and March 1, 2022, in Wuhan Jinyintan Hospital. Three months after TDF treatment, the renal function injury was evaluated with the standard creatinine clearance rate. The urinary levels of α1MG and ß2MG were compared between the initiation of TDF treatment and three months thereafter. Spearman correlation was utilized to analyze the correlation between the urinary expression of α1MG and ß2MG and renal injury in HIV patients. The logistic regression was used to analyze the predictive value of urinary α1MG and ß 2-microglobulin expression in renal injury. RESULTS: Up to the first follow-up, 29 (27.6%) cases of the 105 male HIV patients had varying degrees of renal function injury, including 14 (13.3%) mild injury, 9 (8.6%) moderate injury, and 6 (5.7%) severe injury cases. Patients with severe renal injury had the highest levels of urinary α1MG and ß2MG expression while those with mild injury demonstrated higher levels compared to the non-injury group (P < 0.05). Spearman correlation analysis indicated that urinary α1MG and ß2MG were positively correlated with renal impairment in HIV patients (Rho = -0.568, and -0.732; P < 0.001). The ROC curve analysis demonstrated that the area under the curve (AUC) for urine α1MG and ß2MG in predicting kidney damage among HIV patients were 0.928, 0.916, and 0.889, respectively. The sensitivity values were 96.55%, 82.76%, and 89.66% while the specificity values were 84.07%, 94.51%, and 89.29% for urine α1MG and ß2MG, respectively. CONCLUSION: The expression level of urinary α1MG and ß2MG in HIV patients was significantly higher compared to normal people. Detection of these two indexes can enable early determination of renal injury and its severity in HIV patients.
Assuntos
alfa-Globulinas , Biomarcadores , Infecções por HIV , Tenofovir , Microglobulina beta-2 , Humanos , Masculino , Microglobulina beta-2/urina , alfa-Globulinas/urina , Tenofovir/uso terapêutico , Tenofovir/efeitos adversos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/urina , Infecções por HIV/complicações , Biomarcadores/urina , Pessoa de Meia-Idade , Adulto , Estudos Retrospectivos , Fármacos Anti-HIV/uso terapêutico , Fármacos Anti-HIV/efeitos adversos , Injúria Renal Aguda/urina , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/etiologiaRESUMO
INTRODUCTION: Adherence counselling with point-of-care (POC) drug-level feedback using a novel tenofovir assay may support pre-exposure prophylaxis (PrEP) adherence; however, perceptions of urine testing and its impact on adherence are not well studied. We qualitatively examined how POC tenofovir testing was experienced by transgender women (TGW) in Uganda. METHODS: Within a cluster randomized trial of peer-delivered HIV self-testing, self-sampling for sexually transmitted infections and PrEP among HIV-negative TGW showing overall low PrEP prevention-effective adherence (NCT04328025), we conducted a nested qualitative sub-study of the urine POC assay among a random sample of 30 TGW (August 2021-February 2022). TGW interviews explored: (1) experiences with POC urine tenofovir testing and (2) perceptions of PrEP adherence counselling with drug-level feedback. We used an inductive content analytic approach for analysis. RESULTS: Median age was 21 years (interquartile range 20-24), and 70% engaged in sex work. Four content categories describe how TGW experienced POC urine tenofovir testing: (1) Urine tenofovir testing was initially met with scepticism: Testing urine to detect PrEP initially induced anxiety, with some perceptions of being intrusive and unwarranted. With counselling, however, participants found POC testing acceptable and beneficial. (2) Alignment of urine test results and adherence behaviours: Drug-level feedback aligned with what TGW knew about their adherence. Concurrence between pill taking and tenofovir detection in urine reinforced confidence in test accuracy. (3) Interpretation of urine tenofovir results: TGW familiar with the interpretation of oral-fluid HIV self-tests knew that two lines on the test device signified positivity (presence of HIV). However, two lines on the urine test strip indicated a positive result for non-adherence (absence of tenofovir), causing confusion. Research nurses explained the difference in test interpretation to participants' satisfaction. (4) White coat dosing: Some TGW deliberately chose not to attend scheduled clinic appointments to avoid detecting their PrEP non-adherence during urine testing. They restarted PrEP before returning to clinic, a behaviour called "white coat dosing." CONCLUSIONS: Incorporating POC urine testing into routine PrEP adherence counselling was acceptable and potentially beneficial for TGW but required attention to context. Additional research is needed to identify effective strategies for optimizing adherence monitoring and counselling for this population.
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Fármacos Anti-HIV , Infecções por HIV , Adesão à Medicação , Profilaxia Pré-Exposição , Tenofovir , Pessoas Transgênero , Humanos , Tenofovir/urina , Tenofovir/uso terapêutico , Uganda , Profilaxia Pré-Exposição/métodos , Feminino , Infecções por HIV/prevenção & controle , Infecções por HIV/tratamento farmacológico , Infecções por HIV/urina , Pessoas Transgênero/psicologia , Adulto Jovem , Fármacos Anti-HIV/uso terapêutico , Fármacos Anti-HIV/urina , Masculino , Pesquisa Qualitativa , Adulto , Aconselhamento/métodosAssuntos
Diagnóstico Ausente , Infecções Sexualmente Transmissíveis , Humanos , Infecções por HIV/urina , Comportamento Sexual , Infecções Sexualmente Transmissíveis/diagnóstico , Infecções Sexualmente Transmissíveis/epidemiologia , Infecções Sexualmente Transmissíveis/urina , Estados Unidos/epidemiologia , Urinálise/métodos , Urinálise/estatística & dados numéricos , Diagnóstico Ausente/estatística & dados numéricosRESUMO
OBJECTIVE: Women living with HIV (WLWH) experience psychosocial stress related to social-structural vulnerabilities. To investigate neuroendocrine pathways linking stress and increased cardiovascular disease risk among WLWH, we evaluated associations between psychosocial stress (i.e., perceived stress, posttraumatic stress, and experiences of race- and gender-based harassment) and a composite neuroendocrine biomarker index among WLWH and women without HIV. METHODS: In 2019-2020, Women's Interagency HIV Study participants in Washington, DC completed a questionnaire and provided blood and 12-hour overnight urine samples for testing of serum dehydroepiandrosterone sulfate (DHEA-S) and urinary free cortisol, epinephrine, and norepinephrine. Psychosocial stress was measured using the Perceived Stress Scale, PTSD Checklist-Civilian Version, and Racialized Sexual Harassment Scale. Latent profile analysis was used to classify participants into low (38%), moderate (44%), and high (18%) stress groups. Composite biomarker index scores between 0-4 were assigned based on participants' number of neuroendocrine biomarkers in high-risk quartiles (≥75th percentile for cortisol, epinephrine, and norepinephrine and ≤25th percentile for DHEA-S). We evaluated associations between latent profile and composite biomarker index values using multivariable linear regression, adjusting for socio-demographic, behavioral, metabolic, and HIV-related factors. RESULTS: Among 90 women, 62% were WLWH, 53% were non-Hispanic Black, and median age was 55 years. In full multivariable models, there was no statistically significant association between psychosocial stress and composite biomarker index values among all women independent of HIV status. High (vs. low) psychosocial stress was positively associated with higher mean composite biomarker index values among all monoracial Black women (adjusted ß = 1.32; 95% CI: 0.20-2.43), Black WLWH (adjusted ß = 1.93; 95% CI: 0.02-3.83) and Black HIV-negative women (adjusted ß = 2.54; 95% CI: 0.41-4.67). CONCLUSIONS: Despite a null association in the overall sample, greater psychosocial stress was positively associated with higher neuroendocrine biomarker concentrations among Black women, highlighting a plausible mechanism by which psychosocial stress could contribute to cardiovascular disease risk.
Assuntos
Epinefrina/urina , Infecções por HIV , HIV-1 , Hidrocortisona/urina , Norepinefrina/urina , Estresse Psicológico/urina , Biomarcadores/urina , District of Columbia , Feminino , Infecções por HIV/psicologia , Infecções por HIV/urina , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores SocioeconômicosRESUMO
BACKGROUND: Novel urine biomarkers have enabled the characterization of kidney tubular dysfunction and injury among persons living with HIV, a population at an increased risk of kidney disease. Even though several urine biomarkers predict progressive kidney function decline, antiretroviral toxicity, and mortality in the setting of HIV infection, the relationships among the risk factors for chronic kidney disease (CKD) and urine biomarkers are unclear. METHODS: We assessed traditional and infection-related CKD risk factors and measured 14 urine biomarkers at baseline and at follow-up among women living with HIV in the Women's Interagency Health Study (WIHS). We then used simultaneously adjusted multivariable linear regression models to evaluate the associations of CKD risk factors with longitudinal changes in biomarker levels. RESULTS: Of the 647 women living with HIV in this analysis, the majority (67%) were Black, the median age was 45 years and median follow-up time was 2.5 years. Each traditional and infection-related CKD risk factor was associated with a unique set of changes in urine biomarkers. For example, baseline hemoglobin a1c was associated with worse tubular injury (higher interleukin [IL]-18), proximal tubular reabsorptive dysfunction (higher α1-microglobulin), tubular reserve (lower uromodulin) and immune response to injury (higher chitinase-3-like protein-1 [YKL-40]). Furthermore, increasing hemoglobin a1c at follow-up was associated with further worsening of tubular injury (higher kidney injury molecule-1 [KIM-1] and IL-18), as well as higher YKL-40. HCV co-infection was associated with worsening proximal tubular reabsorptive dysfunction (higher ß2-microglobulin [ß2m]), and higher YKL-40, whereas HIV viremia was associated with worsening markers of tubular and glomerular injury (higher KIM-1 and albuminuria, respectively). CONCLUSIONS: CKD risk factors are associated with unique patterns of biomarker changes among women living with HIV, suggesting that serial measurements of multiple biomarkers may help in detecting and monitoring kidney disease in this setting.
Assuntos
Biomarcadores/urina , Infecções por HIV/urina , Túbulos Renais/patologia , Insuficiência Renal Crônica/urina , Adulto , Antirretrovirais/efeitos adversos , Feminino , Hemoglobinas Glicadas/urina , Infecções por HIV/complicações , Receptor Celular 1 do Vírus da Hepatite A/análise , Humanos , Túbulos Renais/lesões , Pessoa de Meia-Idade , Insuficiência Renal Crônica/complicações , Fatores de RiscoRESUMO
Detection of tuberculosis at the point-of-care (POC) is limited by the low sensitivity of current commercially available tests. We describe a diagnostic accuracy field evaluation of a prototype urine Tuberculosis Lipoarabinomannan Lateral Flow Assay (TB-LAM LFA) in both HIV-positive and HIV-negative patients using fresh samples with sensitivity and specificity as the measures of accuracy. This prototype combines a proprietary concentration system with a sensitive LFA. In a prospective study of 292 patients with suspected pulmonary tuberculosis in Uganda, the clinical sensitivity and specificity was compared against a microbiological reference standard including sputum Xpert MTB/RIF Ultra and solid and liquid culture. TB-LAM LFA had an overall sensitivity of 60% (95%CI 51-69%) and specificity of 80% (95%CI 73-85%). When comparing HIV-positive (N = 86) and HIV-negative (N = 206) patients, there was no significant difference in sensitivity (sensitivity difference 8%, 95%CI -11% to +24%, p = 0.4351) or specificity (specificity difference -9%, 95%CI -24% to +4%, p = 0.2051). Compared to the commercially available Alere Determine TB-LAM Ag test, the TB-LAM LFA prototype had improved sensitivity in both HIV-negative (difference 49%, 95%CI 37% to 59%, p<0.0001) and HIV-positive patients with CD4+ T-cell counts >200cells/µL (difference 59%, 95%CI 32% to 75%, p = 0.0009). This report is the first to show improved performance of a urine TB LAM test for HIV-negative patients in a high TB burden setting. We also offer potential assay refinement solutions that may further improve sensitivity and specificity.
Assuntos
Infecções por HIV/urina , Soropositividade para HIV/urina , Lipopolissacarídeos/urina , Tuberculose/urina , Adulto , Feminino , HIV/patogenicidade , Infecções por HIV/complicações , Infecções por HIV/microbiologia , Infecções por HIV/virologia , Soropositividade para HIV/microbiologia , Soropositividade para HIV/virologia , Humanos , Masculino , Testes Imediatos , Escarro/microbiologia , Escarro/virologia , Tuberculose/complicações , Tuberculose/microbiologia , Tuberculose/virologia , Uganda/epidemiologia , Adulto JovemRESUMO
OBJECTIVES: People living with HIV (PLWH) have a high risk of kidney injury. Measurement of serum creatinine, along with proteinuria, is not sensitive to detect early kidney injury. Here, we investigated novel urinary biomarkers of early renal injury in PLWH. METHODS: We performed a cross-sectional study of 166 antiretroviral-naïve PLWH and 99 HIV-negative persons who all had an estimated glomerular filtration rate > 90 mL/min/1.73 m2 . We compared the levels of seven urinary biomarkers between the two groups using the propensity score matching (PSM) approach and explored the risk factors associated with elevated urinary biomarkers in PLWH. RESULTS: Eighty-three pairs were successfully matched based on PSM. Compared with the HIV-negative group, the HIV-positive group had higher ratios of N-acetyl-ß-D-glucosaminidase (NAG) to urine creatinine (UCr), alpha1-microglobulin (α1-M) to UCr, kidney injury marker-1 (KIM-1) to UCr, neutrophil gelatinase-associated lipocalin to UCr, and epidermal growth factor to UCr, whereas the Tamm-Horsfall protein to UCr ratio and the abnormal albumin to UCr ratio were not significantly different. Positive correlations were observed between HIV RNA level and NAG: UCr (rs = 0.32; P < 0.001) and α1-M:UCr (rs = 0.24; P = 0.002) ratios, and negative correlations were observed between CD4 cell count and NAG:UCr (rs = -0.34; P < 0.001), KIM-1:UCr (rs = -0.16; P = 0.042) and α1-M:UCr (rs = -0.36; P < 0.001) ratios. In multivariate linear regression analyses, older age, lower total cholesterol and higher HIV RNA were independently associated with higher NAG:UCr; older age, lower total cholesterol and lower CD4 cell count were independently associated with higher α1-M:UCr. CONCLUSIONS: In comparioson with HIV-negative participants, PLWH were more likely to have tubular injury. Early antiretroviral treatment might mitigate the development of kidney injury.
Assuntos
Infecções por HIV , Biomarcadores , China/epidemiologia , Estudos Transversais , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/urina , Humanos , Rim , Lipocalina-2RESUMO
HIV-1 persists indefinitely in multiple cellular reservoirs despite antiretroviral therapy. We previously demonstrated HIV-1 compartmentalization in kidney and urine. Here, we further characterized viruses in urine and when available, compared them to those present in semen from HIV-1 positive participants with detectable plasma viremia to further understand the viral dynamics in the upper and lower genitourinary tract.Blood and urine samples were obtained from 19 HIV-1 positive participants. Simultaneous semen samples were obtained from 16 of the 19 participants. HIV-1 envelope (env) gene sequences were obtained by single-genome amplification (SGA) and neighbor-joining trees were constructed using the Kimura 2-parameter model.HIV-1 env gene sequences were amplified from blood in 19/19 (100%) participants, urine in 18/19 (95%) participants, and semen in 12/16 (75%). In individuals from which both urine and semen samples were obtained, differences in viral shedding between the 2 sources were observed, where HIV-1 env sequences could only be amplified from either urine or semen. Longitudinal phylogenetic analysis of urine-derived env sequences from 1 participant demonstrated that urine clusters distinct from blood are maintained over time (20 weeks), consistent with viral compartmentalization and local replication. Comparison of urine and semen derived sequences demonstrated either virus compartmentalization or equilibration.Our results demonstrate that when present, viral compartmentalization in urine persists over time. Comparison of timing of viral shedding in urine and semen samples from our cohort suggest different viral kinetics between the upper and lower genitourinary tract and sequence analysis suggests that HIV-1 populations in urine and semen can either be imported from blood or produced locally.
Assuntos
Infecções por HIV/virologia , HIV-1/genética , Sêmen/virologia , Soro/virologia , Urina/virologia , Viremia/virologia , Adulto , Feminino , Amplificação de Genes , Infecções por HIV/sangue , Infecções por HIV/urina , Humanos , Masculino , Filogenia , Carga Viral , Viremia/sangue , Viremia/urina , Eliminação de Partículas ViraisRESUMO
Merkel cell polyomavirus (MCPyV) viral protein 1 (VP1) is the capsid protein that mediates virus attachment to host cell receptors and is the major immune target. Given the limited data on MCPyV VP1 mutations, the VP1 genetic variability was examined in 100 plasma and 100 urine samples from 100 HIV+ individuals. Sequencing of VP1 DNA in 17 urine and 17 plasma specimens, simultaneously MCPyV DNA positive, revealed that 27 samples displayed sequences identical to VP1 of MCC350 strain. VP1 from two urine specimens had either Thr47Ser or Ile115Phe substitution, whereas VP1 of one plasma contained Asp69Val and Ser251Phe substitutions plus deletion (∆) of Tyr79. VP1 DNA in the remaining samples had mutations encoding truncated protein. Three-dimensional prediction models revealed that Asp69Val, Ser251Phe, and Ile115Phe caused neutral effects while Thr47Ser and Tyr79∆ produced a deleterious effect reducing VP1 stability. A549 cells infected with urine or plasma samples containing full-length VP1 variants with substitutions, sustained viral DNA replication and VP1 expression. Moreover, medium harvested from these cells was able to infect new A549 cells. In cells infected by samples with truncated VP1, MCPyV replication was hampered. In conclusion, MCPyV strains with unique mutations in the VP1 gene are circulating in HIV+ patients. These strains display altered replication efficiency compared to the MCC350 prototype strain in A549 cells.
Assuntos
Substituição de Aminoácidos , Proteínas do Capsídeo/química , Infecções por HIV/virologia , Poliomavírus das Células de Merkel/fisiologia , Infecções por Polyomavirus/virologia , Células A549 , Adulto , Idoso , Proteínas do Capsídeo/genética , Estudos Transversais , Feminino , Infecções por HIV/sangue , Infecções por HIV/urina , HIV-1/patogenicidade , Humanos , Masculino , Poliomavírus das Células de Merkel/genética , Pessoa de Meia-Idade , Modelos Moleculares , Plasma/virologia , Infecções por Polyomavirus/sangue , Infecções por Polyomavirus/genética , Infecções por Polyomavirus/urina , Conformação Proteica , Estabilidade Proteica , Urina/virologia , Replicação Viral , Adulto JovemRESUMO
There are increasing reports of antiretroviral therapy (ART) drug-related kidney dysfunction. Traditional markers of kidney dysfunction such as urine protein/creatinine ratio and estimated glomerular filtration rate (eGFR) have thus far proven ineffective at detecting some sub-clinical forms of ART-related kidney injury. This is a cross-sectional examination of 114 people living with HIV (PLWH), either naïve (N =104) or treatment experienced (N =10). Urinary kidney injury molecule-1 (KIM-1 ng/mg) thresholds were estimated using electrochemiluminescent assays from stored urine samples and normalised for urinary creatinine excretion (KIM-1/Cr). Correlation coefficients and predictors of kidney tubular injury were compared and derived for both adjusted and unadjusted urinary KIM-1/CR (ng/mg). In PLWH (both ART-naïve and treatment experienced) had a higher baseline unadjusted and adjusted median (≥3.7 ng/mg) and upper tertile (≥6.25 ng/mg) urinary KIM-1/Cr levels compared to either non-normal volunteers (0.39 ng/mg) or those with acute kidney injury in the general population (0.57 ng/mg). When upper tertile KIM-1/Cr (≥6.25 ng/mg) was utilised as a marker of kidney injury, eGFR (ml/min/1.73 m2), white Caucasian ethnicity, and protease inhibitor exposure were significantly associated with increased risk of kidney injury in multivariate analyses (odds ratio 0.91, confidence interval [CI] 0.68-0.98, P = 0.02; odds ratio 8.9, CI 1.6-48.6, p = 0.01; and odds ratio 0.05, CI 0.03-0.9, p =0.04, respectively). We found a significant degree of sub-clinical kidney injury (high unadjusted and adjusted KIM-1/Cr) in PLWH with normal kidney function (eGFR ≥60 ml/min/1.73 m2). We also found a higher baseline KIM-1/Cr (ng/mg) in our study cohort than reported both in normal volunteers and patients with kidney injury in the general population.
Assuntos
Terapia Antirretroviral de Alta Atividade/efeitos adversos , Infecções por HIV/sangue , Infecções por HIV/urina , Receptor Celular 1 do Vírus da Hepatite A/sangue , Insuficiência Renal/induzido quimicamente , Adulto , Biomarcadores/sangue , Biomarcadores/urina , Creatinina/urina , Infecções por HIV/tratamento farmacológico , Humanos , Testes de Função Renal , Masculino , Pessoa de Meia-IdadeRESUMO
An accurate urine test for diverse populations with active tuberculosis could be transformative for preventing TB deaths. Urinary liporabinomannan (LAM) testing has been previously restricted to HIV co-infected TB patients. In this study we evaluate urinary LAM in HIV negative, pediatric and adult, pulmonary and extrapulmonary tuberculosis patients. We measured 430 microbiologically confirmed pretreatment tuberculosis patients and controls from Peru, Guinea Bissau, Venezuela, Uganda and the United States using three monoclonal antibodies, MoAb1, CS35, and A194, which recognize distinct LAM epitopes, a one-sided immunoassay, and blinded cohorts. We evaluated sources of assay variability and comorbidities (HIV and diabetes). All antibodies successfully discriminated TB positive from TB negative patients. ROAUC from the average of three antibodies' responses was 0.90; 95% CI 0.87-0.93, 90% sensitivity, 73.5% specificity (80 pg/mL). MoAb1, recognizing the 5-methylthio-D-xylofuranose(MTX)-mannose(Man) cap epitope, performed the best, was less influenced by glycosuria and identified culture positive pediatric (N = 19) and extrapulmonary (N = 24) patients with high accuracy (ROAUC 0.87, 95% CI 0.77-0.98, 0.90 sensitivity 0.80 specificity at 80 pg/mL; ROAUC = 0.96, 95% CI 0.92-0.99, 96% sensitivity, 80% specificity at 82 pg/mL, respectively). The MoAb1 antibody, recognizing the MTX-Man cap epitope, is a novel analyte for active TB detection in pediatric and extrapulmonary disease.
Assuntos
Lipopolissacarídeos/análise , Tuberculose/diagnóstico , Tuberculose/imunologia , Adulto , Coinfecção/urina , Epitopos/imunologia , Feminino , Guiné-Bissau , Infecções por HIV/urina , Humanos , Imunoensaio/métodos , Testes Imunológicos/métodos , Lipopolissacarídeos/imunologia , Lipopolissacarídeos/urina , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/imunologia , Peru , Sistemas Automatizados de Assistência Junto ao Leito , Sensibilidade e Especificidade , Tuberculose/classificação , Tuberculose Pulmonar/microbiologia , Uganda , Estados Unidos , VenezuelaRESUMO
BACKGROUND: Few studies have evaluated the mortality rate in individuals with HIV initiating antiretroviral therapy (ART), undergoing screening with combined or repeated rapid tests for tuberculosis (TB). METHODS: All individuals with HIV starting ART, irrespective of the presence of TB-related symptoms, received two consecutive Xpert tests plus a rapid test for the detection of mycobacterial lipoarabinomannan in urine (LAM). Mortality was evaluated by Kaplan-Meier analysis using the log-rank test in univariate analyses and Cox regression models with time-dependent covariates in multivariate analyses. RESULTS: Among 972 individuals screened with combined tests, 98 (10.1%) tested positive for TB with Xpert, LAM, or both. At the end of the study, 780 (80.2%) had completed 2 years of follow-up, 39 (4.0%) had died, and 153 (15.7%) were lost to follow-up. In the multivariate analyses, the factors significantly associated with mortality were missed ART (hazard ratio (HR) 7.05, 95% confidence interval (CI) 2.33-21.35), symptomatic HIV disease (WHO-HIV stage >1) (HR 3.31, 95% CI 1.28-8.54), and low CD4 count (<200/mm3) (HR 2.72, 95% CI 1.21-6.13), with no significant effect of TB status. In the subgroup of the 98 TB-positive individuals, only missed ART (HR 4.12, 95% CI 1.03-16.46) and missed anti-TB treatment (HR 9.25, 95% CI 2.65-32.28) were significantly associated with mortality. CONCLUSIONS: A low mortality rate was observed among individuals with HIV undergoing systematic testing for TB at initiation of ART. After adjusting for confounders, mortality was significantly associated with missed ART, advanced disease, and missed anti-TB treatment. These findings reinforce the need to promote early diagnosis of HIV and the adoption of screening strategies for TB that prevent presentation with severe disease.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/mortalidade , Tuberculose Pulmonar/complicações , Adulto , Feminino , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/urina , Humanos , Lipopolissacarídeos/urina , Masculino , Programas de Rastreamento , Moçambique/epidemiologia , Sensibilidade e Especificidade , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/urinaRESUMO
OBJECTIVE: Medium-grade proteinuria (100-500 mg/g creatinine) is common among people living with HIV/AIDS (PLWHA) but is often undetected or ignored. This prospective, observational cohort study examined medium-grade proteinuria as a risk factor for markers of chronic kidney disease (CKD). METHODS: Quantitative urine samples were collected from 241 PLWHA without known renal disease at baseline between January 2009 and February 2011 and at follow-up 240 weeks later. Multivariate analysis was performed to assess medium-grade proteinuria as a risk factor for incident markers of CKD (estimated glomerular filtration rate < 60 mL/min/1.73 m2 , albuminuria, phosphaturia). RESULTS: Incident markers of CKD were identified in 33 patients (14%), of whom 24 (74%) had medium-grade proteinuria at baseline. Of these, 22 even had proteinuria of < 200 mg/g creatinine. Multivariate analysis showed an adjusted relative risk (aRR) of 2.4 for patients with baseline medium-grade proteinuria to develop signs of CKD. Age was identified as an additional independent predictor. By testing for interaction, tenofovir disoproxil fumarate (TDF)-independent proteinuria was strongly associated with incident CKD markers (aRR = 12.1). CONCLUSION: Medium-grade proteinuria of 100-500 mg/g creatinine is both frequent in PLWHA and a significant risk factor for developing markers of CKD, especially in the absence of TDF. Relevant risk seems to be associated with proteinuria levels as low as 100-200 mg/g creatinine. Current guidelines recommend specific action for proteinuria exceeding 135-200 mg/g but still will miss a relevant number of PLWHA potentially at risk for CKD. An even lower cut-off to trigger nephrological work-up and potentially renoprotective interventions appears to be indicated.
Assuntos
Fármacos Anti-HIV/efeitos adversos , Biomarcadores/urina , Infecções por HIV/tratamento farmacológico , Proteinúria/diagnóstico , Insuficiência Renal Crônica/diagnóstico , Tenofovir/efeitos adversos , Adulto , Fatores Etários , Progressão da Doença , Feminino , Taxa de Filtração Glomerular , Infecções por HIV/complicações , Infecções por HIV/urina , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Guias de Prática Clínica como Assunto , Estudos Prospectivos , Proteinúria/etiologia , Insuficiência Renal Crônica/etiologia , Tenofovir/uso terapêuticoRESUMO
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 JovemRESUMO
Currently, most HIV tests are performed with blood samples, or alternatively saliva samples are used for HIV testing. Simple HIV tests need to be performed in hospitals or other medical agencies instead of more invasive HIV blood tests. To enable point-of-care (POC) HIV diagnostics, based on a recently developed lateral flow strip for HIV urine testing, a microfluidic immunoassay cassette with a handheld optical reader is developed. Based on lateral flow strip with gold colloid reporter, the integrated immunoassay cassette can perform sample introduction, metering, discharging, applying and detection which simplifies HIV testing. An indicator is incorporated into the cassette to guide sample introduction based on color change, and further, the excess test sample is stored inside the sealed cassette to avoid any contamination. The low-cost handheld optical reader can provide a test result within a few seconds, which is useful for simple, sensitive and affordable HIV onsite detection. Instead of using normal white LEDs, a customized back light module embedded with green LEDs is adopted to illuminate the lateral flow strip with an appropriate working current to achieve optimal performance. Compared to the standard lateral flow strips using a benchtop reader, with the disposable immunoassay cassette assisted by the handheld optical reader, more convenient, easier-to-operate, and more affordable HIV urine testing can be achieved in POC diagnostics.
Assuntos
Infecções por HIV/urina , Imunoensaio/instrumentação , Testes Imediatos , Urinálise/instrumentação , Custos e Análise de Custo , Infecções por HIV/diagnóstico , Humanos , Imunoensaio/economia , Urinálise/classificação , Urinálise/economiaRESUMO
BACKGROUND: Data on bone health and renal impairment in people with human immunodeficiency virus (HIV) in resource-limited settings are limited. The primary aim of this study was to investigate the potential role of calcaneal quantitative ultrasonography (QUS) in predicting bone mineral density (BMD) reduction in a population of Ugandan HIV-infectedâ â individuals receiving long-term antiretroviral therapy; the secondary end point was to assess the prevalence of proximal tubular dysfunction and the correlation between elevated urinary retinol-binding protein-urinary creatinine ratio (uRBP/uCr) and reduced BMD. METHODS: We conducted a cross-sectional study at the Infectious Diseases Institute, Kampala, Uganda. We included 101 HIV-infectedâ adults who had been receiving continuous antiretroviral therapy forâ ≥10 years and had undergone dual-energy x-ray absorptiometry (DXA) during the previous 12 months. All patients underwent calcaneal QUS evaluation and urine sample collection. RESULTS: DXA BMD measurements were significantly associated (Pâ <â .01) with calcaneal speed of sound, broadband ultrasound attenuation, and QUS index. Forty-seven individuals (47%) had abnormal uRBP/uCr values. A significant inverse correlation was observed between uRBP/uCr and DXA T scores (lumbar [Pâ =â .03], femoral neck [Pâ <â .001], and total hip [Pâ =â .002]). CONCLUSIONS: Calcaneal QUS results showed a moderate correlation with DXA outputs. The identified high prevalence of subclinical tubular impairment also highlights the importance of expanding access to tenofovir disoproxil fumarate-sparing regimens in resource-limited settings.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Calcâneo/diagnóstico por imagem , Creatinina/urina , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Proteínas de Ligação ao Retinol/urina , Absorciometria de Fóton , Adulto , Densidade Óssea , Estudos Transversais , Feminino , Infecções por HIV/diagnóstico por imagem , Infecções por HIV/urina , Humanos , Nefropatias/complicações , Nefropatias/diagnóstico , Túbulos Renais Proximais , Masculino , Projetos Piloto , Uganda , UltrassonografiaRESUMO
Point-of-care urine-lipoarabinomannan (LAM) Alere Determine TB-LAM assay has shown utility diagnosing tuberculosis (TB) in HIV-positive, severely immunocompromised, TB-symptomatic patients. We assessed LAM results in severely immunocompromised patients, who had LAM systematically performed at new or follow-up HIV consultations. This was a prospective, observational study on consecutive ambulatory, > 15-year-old HIV-positive patients with CD4 < 100 cells/µL in Mozambique. Clinical assessments and LAM were performed for all and microscopy, Xpert, sputum culture, and chest X-ray for LAM-positive participants. Patients were followed up for 6 months. Of 360 patients, half were ART-naive. Lipoarabinomannan positivity was 11.9% (43/360), higher among symptomatic patients compared with asymptomatic: 18.5% (30/162), and 6.6% (13/198), respectively, P = 0.001. Tuberculosis was bacteriologically confirmed in 6/35 LAM-positive patients (2 of them asymptomatic). Lipoarabinomannan positivity was associated with higher risk of mortality (adjusted odds ratio [aOR]: 4.6, 95% CI: 1.3-15.6, P = 0.015). Systematic urine-LAM allows for rapid TB treatment initiation in severely immunocompromised HIV ambulatory patients and identifies patients at a higher risk of death.