Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 6.395
Filtrar
1.
BMC Infect Dis ; 20(1): 572, 2020 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-32758158

RESUMO

BACKGROUND: Management of co-infections including cryptococcal meningitis, tuberculosis and other opportunistic infections in persons living with HIV can lead to complex polypharmacotherapy and increased susceptibility to drug-drug interactions (DDIs). Here we characterize the frequency and types of potential DDIs (pDDIs) in hospitalized HIV patients presenting with suspected cryptococcal or tuberculous meningitis. METHODS: In a retrospective review of three cryptococcal meningitis trials between 2010 and 2017 in Kampala, Uganda, medications received over hospitalization were documented and pDDI events were assessed. IBM Micromedex DRUGDEX® online drug reference system was used to identify and describe potential interactions as either contraindicated, major, moderate or minor. For antiretroviral DDIs, the Liverpool Drug Interactions Checker from the University of Liverpool was also used to further describe interactions observed. RESULTS: In 1074 patients with suspected meningitis, pDDIs were present in 959 (overall prevalence = 89.3%) during the analyzed 30 day window. In total, 278 unique interacting drug pairs were identified resulting in 4582 pDDI events. Of all patients included in this study there was a mean frequency of 4.27 pDDIs per patient. Of the 4582 pDDI events, 11.3% contraindicated, 66.4% major, 17.4% moderate and 5% minor pDDIs were observed. Among all pDDIs identified, the most prevalent drugs implicated were fluconazole (58.4%), co-trimoxazole (25.7%), efavirenz (15.6%) and rifampin (10.2%). Twenty-one percent of the contraindicated pDDIs and 27% of the major ones involved an antiretroviral drug. Increased likelihood of QT interval prolongation was the most frequent potential clinical outcome. Dissonance in drug interaction checkers was noted requiring clinicians to consult more than one database in making clinical decisions about drug combinations. CONCLUSIONS: The overall prevalence of pDDIs in this population is high. An understanding of drug combinations likely to result in undesired clinical outcomes, such as QT interval prolongation, is paramount. This is especially important in resource limited settings where availability of therapeutic drug monitoring and laboratory follow-up are inconsistent. Adequate quantification of the increased likelihood of adverse clinical outcomes from multiple drug-drug interactions of the same kind in a single patient is needed to aid clinical decisions in this setting.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Antirretrovirais/uso terapêutico , Antifúngicos/uso terapêutico , Coinfecção/tratamento farmacológico , Cryptococcus neoformans , HIV-1 , Hospitalização , Meningite Criptocócica/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/virologia , Adolescente , Adulto , Coinfecção/virologia , Interações Medicamentosas , Monitoramento de Medicamentos/métodos , Feminino , Humanos , Masculino , Meningite Criptocócica/diagnóstico , Meningite Criptocócica/microbiologia , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Uganda/epidemiologia , Adulto Jovem
2.
BMC Infect Dis ; 20(1): 593, 2020 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-32787798

RESUMO

BACKGROUND: Tuberculosis is a serious health risk, for people living with human immune deficiency virus worldwide, and the burden of TB/HIV infection is still high in Ethiopia in particular. Therefore, the aim of this study was to determine the predictors of tuberculosis infection among adults visiting anti-retroviral treatment center in East and West Gojjam, northwest, Ethiopia. METHODS: Institution based unmatched case-control study was employed to determine the predictors of tuberculosis infection among adults visiting anti-retroviral treatment center in east and west Gojjam, Northwest, Ethiopia from March 7-April 15, 2017. Just about 552 participants were participated in the study (139 Cases and 413 controls). Cases were confirmed with active TB and infected with HIV, and controls were HIV positive adults with non-TB. All cases in each health facility who confirmed by acid-fast bacilli, culture and gene expert were considered as TB positive. However, controls were selected by using simple random sampling technique through the above diagnostic criteria and the data were collected with Face to face interview as well as patient medical record were utilized, and the quality of the data were assured, checked, coded, cleaned and entered in EPI-Data version 3.1 and exported to SPSS version 20 for the analysis. RESULT: Of the total sample (556), just about 552(99.2%) were participated in the study. 47.5% were females and 58.9% were rural dweller. Behavioral and modifiable biological risk factors: alcohol users (AOR = 2.33; 95%CI:1.34,4.07), BMI < 18.5 kg/m2 (AOR = 3.03;95%CI:1.79,5.14), CD4 count ≤200 cells/µl (AOR = 2.34;95%CI:1.89,2.79) and between 201 and 499 cells/µl (AOR = 2.63; 95%CI: 1.01,6.84), bedridden and ambulatory (AOR = 3.3;95%CI:1.70,6.29 and AOR = 8.2;95%CI:4.34,15.64), respectively. TB history in the family (AOR = 3.00; 95%CI: 1.57, 5.74) were predictors for TB infection. Taking CPT (AOR = 0.36; 95%CI: 0.21, 0.62) and having early WHO clinical stage I or II (AOR = 0.34; 95%CI: 0.20, 0.56) had protective effect against TB infection. CONCLUSION: From this study, it has been concluded that alcohol users, BMI < 18.5 kg/m2, CD4 count < 499 cells/µl, bedridden and ambulatory and TB history were predictors for TB-HIV co-infected adults. Strengthen screening more frequently, CPT Prophlaxysis and treated promptly important to reduce TB co-morbidity.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Antirretrovirais/uso terapêutico , Coinfecção/epidemiologia , HIV , Mycobacterium tuberculosis/genética , Tuberculose Pulmonar/epidemiologia , Adolescente , Adulto , Consumo de Bebidas Alcoólicas , Índice de Massa Corporal , Contagem de Linfócito CD4 , Estudos de Casos e Controles , Etiópia/epidemiologia , Feminino , Humanos , Masculino , Mycobacterium tuberculosis/isolamento & purificação , Prognóstico , População Rural , Adulto Jovem
3.
PLoS One ; 15(8): e0237162, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32750098

RESUMO

Viral diversity is an important feature of hepatitis C virus (HCV) infection and an important predictor of disease progression and treatment response. HIV/HCV co-infection is associated with enhanced HCV replication, increased fibrosis, and the development of liver disease. HIV also increases quasispecies diversity of HCV structural genes, although limited data are available regarding the impact of HIV on non-structural genes of HCV, particularly in the absence of direct-acting therapies. The genetic diversity and presence of drug resistance mutations within the RNA-dependent RNA polymerase (NS5B) gene were examined in 3 groups of women with HCV genotype 1a infection, including those with HCV mono-infection, antiretroviral (ART)-naïve women with HIV/HCV co-infection and CD4 cell count <350 cells/mm3, and ART-naïve women with HIV/HCV co-infection and CD4 cell count ≥350 cells/mm3. None had ever been treated for HCV infection. There was evidence of significant diversity across the entire NS5B gene in all women. There were several nucleotides and amino acids with distinct distributions across the three study groups, although no obvious clustering of NS5B sequences was observed based on HIV co-infection or CD4 cell count. Polymorphisms at amino acid positions associated with resistance to dasabuvir and sofosbuvir were limited, although the Q309R variant associated with ribavirin resistance was present in 12 individuals with HCV mono-infection, 8 HIV/HCV co-infected individuals with CD4 <350 cells/mm3, and 12 HIV/HCV co-infected individuals with CD4 ≥350 cells/mm3. Previously reported fitness altering mutations were rare. CD8+ T cell responses against the human leukocyte antigen (HLA) B57-restricted epitopes NS5B2629-2637 and NS5B2936-2944 are critical for HCV control and were completely conserved in 44 (51.8%) and 70 (82.4%) study participants. These data demonstrate extensive variation across the NS5B gene. Genotypic variation may have a profound impact on HCV replication and pathogenesis and deserves careful evaluation.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/genética , Coinfecção/genética , Variação Genética , HIV , Hepacivirus/genética , Hepatite C/genética , Proteínas não Estruturais Virais/genética , Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/virologia , Adulto , Sequência de Aminoácidos , Antivirais/uso terapêutico , Contagem de Linfócito CD4 , Estudos de Coortes , Coinfecção/tratamento farmacológico , Coinfecção/virologia , Farmacorresistência Viral/genética , Feminino , Genótipo , Hepatite C/tratamento farmacológico , Hepatite C/virologia , Humanos , Filogenia , RNA Replicase/genética , RNA Viral/genética , RNA Viral/isolamento & purificação , Sofosbuvir/uso terapêutico , Sulfonamidas/uso terapêutico , Uracila/análogos & derivados , Uracila/uso terapêutico
4.
BMC Infect Dis ; 20(1): 471, 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32615931

RESUMO

BACKGROUND: Pertussis is a highly contagious disease of public health interest caused by the bacterium Bordetella pertussis. Although its incidence has decreased substantially after the introduction of a vaccination, the burden of the disease remains high. Although the paroxysmal phase is highly disabling, complications are uncommon and more prevalent in children than in adults. The most frequent neurological complication is encephalopathy, but seizures, paresis, paraplegia, ataxias, aphasias, and decerebration postures have also been described. The complication of decerebration postures has not been previously reported in adults. CASE PRESENTATION: We present a video case of an adult HIV patient with severe coughing paroxysms, post-tussive emesis and syncope, whose workup confirmed the diagnosis of a B. pertussis respiratory infection. During hospitalization, he had fluctuant encephalopathy and post-tussive decerebration postures following paroxysms. He was treated with antibiotic therapy and finally sent home without residual neurological deficits. CONCLUSION: This case illustrates the biological plausibility of neurologic complications of pertussis in adults, which, albeit rare, can cause important morbidities. Future research should explore whether there are differences in the clinical presentation, risk factors and pathophysiology of the disease among adults or interventions aimed at preventing or treating pertussis encephalopathy.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/complicações , Bordetella pertussis/genética , Encefalopatias/complicações , Estado de Descerebração/complicações , HIV , Coqueluche/complicações , Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/virologia , Antibacterianos/uso terapêutico , Bordetella pertussis/isolamento & purificação , Encefalopatias/tratamento farmacológico , Encefalopatias/microbiologia , Estado de Descerebração/tratamento farmacológico , Estado de Descerebração/microbiologia , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Fatores de Risco , Resultado do Tratamento , Coqueluche/tratamento farmacológico , Coqueluche/microbiologia
5.
BMC Infect Dis ; 20(1): 551, 2020 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-32727383

RESUMO

BACKGROUND: Talaromyces marneffei (TM) is a dimorphic fungus mainly prevalent in Southeast Asian countries, which often causes disseminated life-threatening infection. TM infection often occurs in HIV/AIDS patients even in the antiretroviral therapy (ART) era. However, there has as yet, not been a systematic analysis of the prevalence of TM infection in HIV-infected populations in Asia. METHODS: In this study, we searched Pubmed, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), and WanFang from inception to 21 November 2018 for studies reporting TM infection in people living with HIV/AIDS (PLWHA). Our meta-analysis included studies investigating the prevalence of TM infection in PLWHA. Reviews, duplicate studies, and animal studies were excluded. A random effects model was used to estimate pooled prevalence, and meta-regression analysis was conducted to explore potential factors for heterogeneity. RESULTS: 159,064 patients with HIV infection in 33 eligible studies were included in our meta-analysis. The pooled prevalence of TM infection in PLWHA was 3.6%. Vietnam had the highest prevalence (6.4%), followed by Thailand (3.9%), China (3.3%), India (3.2%) and Malaysia (2.1%). In China, TM infection was most prevalent in South China (15.0%), while the burden in Southwest China was not very heavy (0.3%). CD4+ T-cell counts below 200 cells/mm3 contributed to the increased risk of TM infection in PLWHA (OR 12.68, 95%CI: 9.58-16.77). However, access to ART did not significantly decrease the risk of TM infection in PLWHA. CONCLUSIONS: The burden of TM infection in Asia is heavy, and varies from region to region. PLWHA in lower latitude areas are more likely to suffer from TM infection. Optimization of diagnostic tools and universal screening for TM in vulnerable people to ensure early case detection and prompt antifungal treatment should be considered.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Fármacos Anti-HIV/uso terapêutico , HIV , Micoses/epidemiologia , Talaromyces/isolamento & purificação , Infecções Oportunistas Relacionadas com a AIDS/virologia , Ásia Sudeste/epidemiologia , Linfócitos T CD4-Positivos , China/epidemiologia , Humanos , Índia/epidemiologia , Contagem de Linfócitos , Micoses/microbiologia , Prevalência
6.
Medicine (Baltimore) ; 99(29): e21141, 2020 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-32702867

RESUMO

BACKGROUND: Toxoplasma encephalitis (TE) is one of the main opportunistic infections in acquired immunodeficiency syndrome (AIDS) patients, and represents a social burden due to its high prevalence and morbidity. Concomitant antiretroviral therapy (ART), together with effective anti- toxoplasma combination therapy, is an effective strategy to treat AIDS-associated TE (AIDS/TE) patients. However, the timing for the initiation of ART after diagnosis of TE remains controversial. We therefore designed the present study to determine the optimal timing for ART initiation in AIDS/TE patients. METHODS/DESIGN: This trial is a 17-center, randomized, prospective clinical study with 2 parallel arms. A total of 200 participants will be randomized at a 1:1 ratio into the 2 arms: the early ART initiation (≤14 days after TE diagnosis) arm and the deferred ART (>14 days after TE diagnosis) arm. The primary outcome will be the difference of mortality between the 2 arms at 48 weeks. The secondary outcomes will be the differences between the 2 arms in the changes of CD4+ counts from baseline to week 48, the rate of virologic suppression (HIV ribonucleic acid <50 copies/mL) from baseline to week 48, the incidence of TE-associated immune reconstitution inflammatory syndrome during the study period, and the incidence of adverse effects during the study period. DISCUSSION: This present trial aims to evaluate the optimal timing for ART initiation in AIDS/TE patients, and will provide strong evidence for AIDS/TE treatment should it be successful. TRIAL REGISTRATION: This trial was registered as one of the 12 trials under the name of a general project at the chictr.gov (http://www.chictr.org.cn/showproj.aspx?proj=35362) on February 1, 2019, and the registration number of the general project is ChiCTR1900021195.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Antirretrovirais/uso terapêutico , Protocolos Clínicos , Fatores de Tempo , Toxoplasmose Cerebral/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/fisiopatologia , Adulto , Infecções por HIV/complicações , Infecções por HIV/fisiopatologia , Humanos , Medicina de Precisão/métodos , Estudos Prospectivos , Toxoplasmose Cerebral/fisiopatologia
7.
BMC Infect Dis ; 20(1): 294, 2020 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-32664847

RESUMO

BACKGROUND: Tuberculosis (TB) is the most common opportunistic infection and the leading cause of death in people living with HIV (PLHIV). HIV-infected children are at a higher risk of TB infection and disease compared to those without HIV. Isoniazid preventive therapy (IPT) is an effective intervention in preventing progression of latent TB infection to active TB. The World Health Organization (WHO) currently recommends that all children aged > 12 months and adults living with HIV in whom active TB has been excluded should receive a 6-months course of IPT as part of a comprehensive package of HIV care. Despite this recommendation, the uptake of IPT among PLHIV has been suboptimal globally. This study sought to determine the factors affecting IPT uptake and completion among HIV-infected children in a large HIV care centre in Nairobi, Kenya. METHOD: This was a cross-sectional mixed methods study comprising of quantitative and qualitative study designs. Medical records of 225 HIV-infected children aged 1 to < 10 years, in care in the Kenyatta National Hospital Comprehensive Care Centre (KNH CCC) were retrospectively reviewed, and 8 purposively selected healthcare providers and 18 consecutively selected caregivers of children were interviewed. RESULTS: IPT uptake among CLHIV in care in the KNH CCC was 68% (152/225) while the treatment completion rate was 82% (94/115). IPT-related health education and counselling were the main facilitators of IPT uptake and completion, while fear of adverse drug reaction, pill burden and lack of an integrated monitoring and evaluation system for IPT were the major barriers. CONCLUSION: The IPT uptake in this study was low and fell short of the set global target of > 90%. The completion rate was however acceptable. There is an urgent need to address the identified barriers.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Antituberculosos/uso terapêutico , Isoniazida/uso terapêutico , Tuberculose Latente/tratamento farmacológico , Tuberculose Latente/prevenção & controle , Adulto , Antituberculosos/efeitos adversos , Criança , Pré-Escolar , Aconselhamento , Estudos Transversais , Feminino , Pessoal de Saúde , Humanos , Lactente , Isoniazida/efeitos adversos , Quênia , Masculino , Pessoa de Meia-Idade , Cooperação do Paciente , Pesquisa Qualitativa , Encaminhamento e Consulta , Estudos Retrospectivos , Resultado do Tratamento , Recusa do Paciente ao Tratamento
8.
BMC Infect Dis ; 20(1): 508, 2020 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-32664854

RESUMO

BACKGROUND: Increased coagulation biomarkers are associated with poor outcomes among people living with HIV (PLHIV). There are few data available from African cohorts demonstrating the effect of antiretroviral therapy (ART) on coagulation biomarkers. METHODS: From March 2014 to October 2014, ART-naïve PLHIV initiating non-nucleoside reverse transcriptase inhibitor-based ART were recruited from seven clinics in western Kenya and followed for up to 12 months. Demographics, clinical history and blood specimens were collected. Logistic regression models adjusted for intrasite clustering examined associations between HIV viral load and D-Dimer at baseline. Mixed linear effects models were used to estimate mean change from baseline to 6 months overall, and by baseline viral load, sex and TB status at enrollment. Mean change in D-dimer at 6 months is reported on the log10 scale and as percentage change from baseline. RESULTS: Among 611 PLHIV enrolled, 66% were female, median age was 34 years (interquartile range (IQR) 29-43 years), 31 (5%) participants had tuberculosis and median viral load was 113,500 copies/mL (IQR: 23,600-399,000). At baseline, 311 (50.9%) PLHIV had elevated D-dimer (> 500 ng/mL) and median D-dimer was 516.4 ng/mL (IQR: 302.7-926.6) (log baseline D-dimer: 2.7, IQR: 2.5-3.0). Higher baseline D-dimer was significantly associated with higher viral load (p < 0.0001), female sex (p = 0.02) and tuberculosis (p = 0.02). After 6 months on ART, 518 (84.8%) PLHIV had achieved viral load < 1000 copies/mL and median D-dimer was 390.0 (IQR: 236.6-656.9) (log D-dimer: 2.6, IQR: 2.4-2.8). Mean change in log D-dimer from baseline to 6 months was - 0.12 (95%CI -0.15, - 0.09) (p < 0.0001) indicating at 31.3% decline (95%CI -40.0, - 23.0) in D-dimer levels over the first 6 months on ART. D-dimer decline after ART initiation was significantly greater among PLHIV with tuberculosis at treatment initiation (- 172.1, 95%CI -259.0, - 106.3; p < 0.0001) and those with log viral load > 6.0 copies/mL (- 91.1, 95%CI -136.7, - 54.2; p < 0.01). CONCLUSIONS: In this large Kenyan cohort of PLHIV, women, those with tuberculosis and higher viral load had elevated baseline D-dimer. ART initiation and viral load suppression among ART-naïve PLHIV in Kenya were associated with significant decrease in D-dimer at 6 months in this large African cohort.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Fármacos Anti-HIV/uso terapêutico , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Inibidores da Transcriptase Reversa/uso terapêutico , Tuberculose/epidemiologia , Infecções Oportunistas Relacionadas com a AIDS/mortalidade , Adulto , Biomarcadores/análise , Biomarcadores/metabolismo , Coagulação Sanguínea/efeitos dos fármacos , Comorbidade , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Seguimentos , Humanos , Quênia/epidemiologia , Masculino , Estudos Prospectivos , Fatores Sexuais , Carga Viral/efeitos dos fármacos , Adulto Jovem
9.
BMC Infect Dis ; 20(1): 407, 2020 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-32527231

RESUMO

BACKGROUND: Cryptococcosis is an opportunistic fungal infection that primarily affects people with advanced HIV/AIDS and is an important cause of morbidity and mortality around the globe. By far the most common presentation of the disease is cryptococcal meningitis (CM), which leads to an estimated 15-20% of all HIV related deaths worldwide, 75% of which are in sub-Saharan Africa. However, to the best of our knowledge there is quite limited reviewed data on the epidemiology of cryptococcal antigenemia in a large HIV-infected population in resource limited settings. METHODS: Articles published in English irrespective of the time of publication were systematically searched using comprehensive search strings from PubMed/Medline and SCOPUS. In addition, Google Scholar and Google databases were searched manually for grey literature. Two reviewers independently assessed study eligibility, extracted data, and assessed risk of bias. The pooled prevalence of cryptococcal antigenemia was determined with 95% confidence interval (CI). RESULTS: Among 2941 potential citations, we have included 22 studies with a total of 8338 HIV positive individuals. The studies were reported in ten different countries during the year (2007-2018). Most of the articles reported the mean CD4 count of the participants below 100 cells/µl. The pooled prevalence of cryptococcal antigenemia at different CD4 count and ART status was at 8% (95%CI: 6-10%) (ranged between 1.7 and 33%). Body mass index (BMI) < 18.5 kg/m2, CD4 count < 100 cells, patients presenting with headache and male gender were reported by two or more articles as an important predictors of cryptococcal antigenemia. CONCLUSIONS: Implementing a targeted screening of HIV patients with low BMI, CD4 count < 100 cells, having headache and males; and treatment for asymptomatic cryptococcal disease should be considered. Additional data is needed to better define the epidemiology of cryptococcal antigenemia and its predictors in resource limited settings in order to optimize the prevention, diagnosis, and treatment strategies.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Alocação de Recursos para a Atenção à Saúde , Meningite Criptocócica/diagnóstico , Meningite Criptocócica/epidemiologia , Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , África ao Sul do Saara/epidemiologia , Humanos , Meningite Criptocócica/tratamento farmacológico , Prevalência , Fatores de Risco
10.
BMC Infect Dis ; 20(1): 449, 2020 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-32590942

RESUMO

BACKGROUND: This study aimed to assess the pharmacokinetic profile of 150 mg rifabutin (RBT) taken every other day (every 48 h) versus 300 mg RBT taken every other day (E.O.D), both in combination with lopinavir/ritonavir (LPV/r), in adult patients with human immunodeficiency virus (HIV) and tuberculosis (TB) co-infection. METHODS: This is a two-arm, open-label, pharmacokinetic, randomised study conducted in Burkina Faso between May 2013 and December 2015. Enrolled patients were randomised to receive either 150 mg RBT EOD (arm A, 9 subjects) or 300 mg RBT EOD (arm B, 7 subjects), both associated with LPV/r taken twice daily. RBT plasma concentrations were evaluated after 2 weeks of combined HIV and TB treatment. Samples were collected just before drug ingestion and at 1, 2, 3, 4, 6, 8, and 12 h after drug ingestion to measure plasma drug concentration using an HPLC-MS/MS assay. RESULTS: The Cmax and AUC0-12h medians in arm A (Cmax = 296 ng/mL, IQR: 205-45; AUC0-12h = 2528 ng.h/mL, IQR: 1684-2735) were lower than those in arm B (Cmax = 600 ng/mL, IQR: 403-717; AUC0-12h = 4042.5 ng.h/mL, IQR: 3469-5761), with a statistically significant difference in AUC0-12h (p = 0.044) but not in Cmax (p = 0.313). No significant differences were observed in Tmax (3 h versus 4 h). Five patients had a Cmax below the plasma therapeutic limit (< 300 ng/mL) in the 150 mg RBT arm, while the Cmax was above this threshold for all patients in the 300 mg RBT arm. Additionally, at 48 h after drug ingestion, all patients had a mycobacterial minimum inhibitory concentration (MIC) above the limit (> 64 ng/mL) in the 300 mg RBT arm, while 4/9 patients had such values in the 150 mg RBT arm. CONCLUSION: This study confirmed that the 150 mg dose of rifabutin ingested EOD in combination with LPV/r is inadequate and could lead to selection of rifamycin-resistant mycobacteria. TRIAL REGISTRATION: PACTR201310000629390, 28th October 2013.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Antibióticos Antituberculose/administração & dosagem , Antibióticos Antituberculose/uso terapêutico , Coinfecção/tratamento farmacológico , Inibidores da Protease de HIV/uso terapêutico , Lopinavir/uso terapêutico , Rifabutina/administração & dosagem , Rifabutina/uso terapêutico , Ritonavir/uso terapêutico , Tuberculose/tratamento farmacológico , Adulto , Antibióticos Antituberculose/efeitos adversos , Antibióticos Antituberculose/sangue , Burkina Faso , Cromatografia Líquida de Alta Pressão , Quimioterapia Combinada , Feminino , Seguimentos , Humanos , Masculino , Testes de Sensibilidade Microbiana , Projetos Piloto , Distribuição Aleatória , Rifabutina/efeitos adversos , Rifabutina/sangue , Espectrometria de Massas em Tandem
11.
N Engl J Med ; 382(25): 2397-2410, 2020 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-32558469

RESUMO

BACKGROUND: In regions with high burdens of tuberculosis and human immunodeficiency virus (HIV), many HIV-infected adults begin antiretroviral therapy (ART) when they are already severely immunocompromised. Mortality after ART initiation is high in these patients, and tuberculosis and invasive bacterial diseases are common causes of death. METHODS: We conducted a 48-week trial of empirical treatment for tuberculosis as compared with treatment guided by testing in HIV-infected adults who had not previously received ART and had CD4+ T-cell counts below 100 cells per cubic millimeter. Patients recruited in Ivory Coast, Uganda, Cambodia, and Vietnam were randomly assigned in a 1:1 ratio to undergo screening (Xpert MTB/RIF test, urinary lipoarabinomannan test, and chest radiography) to determine whether treatment for tuberculosis should be started or to receive systematic empirical treatment with rifampin, isoniazid, ethambutol, and pyrazinamide daily for 2 months, followed by rifampin and isoniazid daily for 4 months. The primary end point was a composite of death from any cause or invasive bacterial disease within 24 weeks (primary analysis) or within 48 weeks after randomization. RESULTS: A total of 522 patients in the systematic-treatment group and 525 in the guided-treatment group were included in the analyses. At week 24, the rate of death from any cause or invasive bacterial disease (calculated as the number of first events per 100 patient-years) was 19.4 with systematic treatment and 20.3 with guided treatment (adjusted hazard ratio, 0.95; 95% confidence interval [CI], 0.63 to 1.44). At week 48, the corresponding rates were 12.8 and 13.3 (adjusted hazard ratio, 0.97 [95% CI, 0.67 to 1.40]). At week 24, the probability of tuberculosis was lower with systematic treatment than with guided treatment (3.0% vs. 17.9%; adjusted hazard ratio, 0.15; 95% CI, 0.09 to 0.26), but the probability of grade 3 or 4 drug-related adverse events was higher with systematic treatment (17.4% vs. 7.2%; adjusted hazard ratio 2.57; 95% CI, 1.75 to 3.78). Serious adverse events were more common with systematic treatment. CONCLUSIONS: Among severely immunosuppressed adults with HIV infection who had not previously received ART, systematic treatment for tuberculosis was not superior to test-guided treatment in reducing the rate of death or invasive bacterial disease over 24 or 48 weeks and was associated with more grade 3 or 4 adverse events. (Funded by the Agence Nationale de Recherches sur le Sida et les Hépatites Virales; STATIS ANRS 12290 ClinicalTrials.gov number, NCT02057796.).


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Antirretrovirais/uso terapêutico , Antituberculosos/uso terapêutico , Infecções por HIV/tratamento farmacológico , Hospedeiro Imunocomprometido , Tuberculose/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Infecções Oportunistas Relacionadas com a AIDS/prevenção & controle , Adulto , Infecções Bacterianas/epidemiologia , Infecções Bacterianas/etiologia , Infecções Bacterianas/prevenção & controle , Contagem de Linfócito CD4 , Feminino , HIV , Infecções por HIV/complicações , Infecções por HIV/mortalidade , Humanos , Masculino , Tuberculose/complicações , Tuberculose/diagnóstico , Tuberculose/mortalidade , Carga Viral
12.
Medicine (Baltimore) ; 99(20): e20146, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32443329

RESUMO

BACKGROUND: An increased frequency of toxoplasma encephalitis, caused by Toxoplasma gondii, has been reported in AIDS patients, especially in those with CD4+ T cell counts <100 cells/µL. Several guidelines recommend the combination of pyrimethamine, sulfadiazine, and leucovorin as the preferred regimen for AIDS-associated toxoplasma encephalitis. However, it is not commonly used in China due to limited access to pyrimethamine and sulfadiazine. The synergistic sulfonamides tablet formulation is a combination of trimethoprim (TMP), sulfadiazine and sulfamethoxazole (SMX), and is readily available in China. Considering its constituent components, we hypothesize that this drug may be used as a substitute for sulfadiazine and TMP-SMX. We have therefore designed the present trial, and propose to investigate the efficacy and safety of synergistic sulfonamides combined with clindamycin for the treatment of toxoplasma encephalitis. METHODS/DESIGN: This study will be an open-labeled, multi-center, prospective, randomized, and controlled trial. A total of 200 patients will be randomized into TMP-SMX plus azithromycin group, and synergistic sulfonamides plus clindamycin group at a ratio of 1:1. All participants will be invited to participate in a 48-week follow-up schedule once enrolled. The primary outcomes will be clinical response rate and all-cause mortality at 12 weeks. The secondary outcomes will be clinical response rate and all-cause mortality at 48 weeks, and adverse events at each visit during the follow-up period. DISCUSSION: We hope that the results of this study will be able to provide reliable evidence for the efficacy and safety of synergistic sulfonamides for its use in AIDS patients with toxoplasma encephalitis. TRIAL REGISTRATION: This study was registered as one of 12 clinical trials under the name of a general project at chictr.gov on February 1, 2019, and the registration number of the general project is ChiCTR1900021195. This study is still recruiting now, and the first patient was screened on March 22, 2019.


Assuntos
Síndrome de Imunodeficiência Adquirida/tratamento farmacológico , Infecções por HIV/tratamento farmacológico , Toxoplasmose Cerebral/complicações , Infecções Oportunistas Relacionadas com a AIDS/complicações , Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Síndrome de Imunodeficiência Adquirida/mortalidade , Adolescente , Adulto , Anti-Infecciosos/uso terapêutico , Antiprotozoários/uso terapêutico , China/epidemiologia , Clindamicina/uso terapêutico , Quimioterapia Combinada/métodos , Feminino , Infecções por HIV/mortalidade , Humanos , Leucovorina/uso terapêutico , Masculino , Estudos Prospectivos , Pirimetamina/uso terapêutico , Sulfadiazina/uso terapêutico , Sulfametoxazol/uso terapêutico , Sulfonamidas/uso terapêutico , T-Linfocitopenia Idiopática CD4-Positiva , Toxoplasma/efeitos dos fármacos , Toxoplasma/parasitologia , Toxoplasmose Cerebral/tratamento farmacológico , Toxoplasmose Cerebral/parasitologia , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico , Complexo Vitamínico B/uso terapêutico
13.
PLoS One ; 15(5): e0232426, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32374773

RESUMO

BACKGROUND: Extrapulmonary tuberculosis is an emerging public health problem among HIV positives compared to the general population. This study aimed to assess the incidence and predictors of extrapulmonary tuberculosis among people living with HIV in selected health facilities in Addis Ababa, Ethiopia, from 01 January 2013 up to 31 December 2018. METHODS: A retrospective cohort study design was employed based on data collected from 566 HIV positive individuals. Data were entered using EpiInfo version 7.1 and analyzed by SPSS version 20. The incidence rate was determined per 100 person-years. Kaplan-Meier estimates used to estimate survivor and the hazard function, whereas log-rank tests used to compare survival curves and hazard across different categories. Cox proportional hazard model was used to identify the predictors and 95%CI of the hazard ratio were computed. P-value<0.05 in the multivariable analysis was considered statistically significant. RESULTS: Five hundred sixty-six HIV positive individuals were followed for 2140.08 person-years. Among them, 72 developed extrapulmonary tuberculosis that gives an incidence rate of 3.36/100 person-years (95%CI = 2.68-4.22). The most frequent forms of extrapulmonary tuberculosis were; lymph node tuberculosis (56%, 41) followed equally by pleural tuberculosis (15%, 11) and disseminated tuberculosis (15%, 11). The majority (70.83%) of the cases occurred within the first year of follow-up. In multivariable Cox regression analysis, baseline WHO stage III/IV (AHR = 2.720, 95%CI = 1.575-4.697), baseline CD4 count<50cells/µl (AHR = 4.073, 95%CI = 2.064-8.040), baseline CD4 count 50-200 cells/µl (AHR = 2.360, 95%CI = 1.314-4.239) and baseline Hgb<10 mg/dl (AHR = 1.979, 95%CI = 1.091-3.591) were the independent risk factors. While isoniazid prophylaxis (AHR = 0.232, 95%CI = 0.095-0.565) and taking antiretroviral drugs (AHR = 0.134, 95%CI = 0.075-0.238) had a protective benefit. CONCLUSION: Extrapulmonary tuberculosis co-infection was common among HIV positive individuals, and mostly occurred in those with advanced immune suppression. The risk decreases in those taking antiretroviral therapy and took isoniazid preventive treatment. Screening of HIV positives for extrapulmonary tuberculosis throughout their follow-up would be important.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Infecções por HIV/complicações , Tuberculose/complicações , Tuberculose/epidemiologia , Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Adolescente , Adulto , Estudos de Coortes , Coinfecção/tratamento farmacológico , Coinfecção/epidemiologia , Intervalo Livre de Doença , Etiópia/epidemiologia , Feminino , Infecções por HIV/tratamento farmacológico , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Tuberculose/tratamento farmacológico , Adulto Jovem
14.
PLoS One ; 15(4): e0229757, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32310961

RESUMO

INTRODUCTION: Even though use of antiretroviral therapy (HAART) decreases the incidence of opportunistic infections (OIs) they are continuing to be a major cause of morbidity and mortality. Studies concerning this problem are scarce in Eastern Africa. The aim of this study was to determine the incidence and predictors of OIs after initiation of HAART in Ethiopia. METHODS: A health facility based single centered cohort study using structured data extraction sheet was conducted. The study population was all HIV positive ART naive adolescents and adults who started HAART between January 2009 and May 2012. Simple random sampling technique was used to select 317 patients from the record. Multivariate binary logistic regression model was used to determine factors for the occurrence of OIs after initiation of HAART. RESULTS: The incidence of OIs after HAART was 7.5 cases/100person years. Tuberculosis, oral candidiasis, pneumonia and toxoplasmosis were the leading OIs after HAART. A bed ridden functional status at initiation of HAART, presence of OIs before HAART, non-adherence and low hemoglobin level were predictors for the occurrence of OIs after HAART. CONCLUSION: The incidence of OIs after HAART was higher than in previous studies. Patients with the identified risk factors need strict follow up to reduce the morbidity and mortality attributed to OIs. Earlier initiation of HAART before advanced immune suppression, better management of TB and extended baseline assessment could help to reduce opportunistic infections and mortality after the initiation of HAART in Ethiopian patients.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Candidíase/tratamento farmacológico , Infecções por HIV/tratamento farmacológico , Pneumonia/tratamento farmacológico , Tuberculose/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/complicações , Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Infecções Oportunistas Relacionadas com a AIDS/virologia , Adolescente , Adulto , Idoso , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Candidíase/complicações , Candidíase/microbiologia , Candidíase/virologia , Estudos de Coortes , Etiópia/epidemiologia , Feminino , HIV/patogenicidade , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Infecções por HIV/virologia , Hemoglobinas/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia/complicações , Pneumonia/microbiologia , Pneumonia/virologia , Tuberculose/complicações , Tuberculose/microbiologia , Tuberculose/virologia , Adulto Jovem
15.
BMC Infect Dis ; 20(1): 309, 2020 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-32334521

RESUMO

BACKGROUND: Clinical manifestations of extraneural infection with the pork tapeworm Taenia solium typically affect the muscles, eyes, alimentary canal, and/or subcutaneous tissues. Children living with HIV are at increased risk for more widespread and severe manifestations of food-borne opportunistic infections, including T. solium, due to fluctuating levels of immunosuppression. We present a case of disseminated T. solium in a HIV-positive child with Kaposi sarcoma living in Tanzania with cysticercosis presenting as widespread subcutaneous nodules. CASE PRESENTATION: A 4-year-old HIV-positive boy in Southern Tanzania presented for evaluation of > 30 violaceous skin lesions, few subcutaneous nodules, and a circumferential violaceous penile lesion which rapidly grew after initiation of ART. The patient was clinically diagnosed with Kaposi sarcoma and started on chemotherapy with bleomycin, vincristine, and doxorubicin. He completed 10 cycles of chemotherapy, with full resolution of the violaceous skin and penile lesions but persistence of his subcutaneous nodules, thus paclitaxel was added. After 12 additional cycles of paclitaxel, his subcutaneous nodules enlarged, and biopsy of a scapular subcutaneous nodule was performed. Histopathology revealed a cystic structure with a central larval scolex and serrated spiral canal consistent with T. solium, which confirmed a diagnosis of disseminated cysticercosis. He completed a 10-day course of praziquantel and albendazole with resolution of the subcutaneous nodules. CONCLUSIONS: Disseminated cysticercosis is an unusual opportunistic infection which can present as subcutaneous nodules without other typical cysticercosis symptoms. Immunosuppression - from HIV and/or chemotherapy - may unmask cysticercosis in children in endemic regions and result in more severe manifestations of this disease. Cysticercosis should remain on a clinician's differential for subcutaneous nodules, especially in children living with HIV. Cysticercosis can mimic Kaposi sarcoma, and histopathology is essential to accurately diagnose and manage patients with concerning skin lesions.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/parasitologia , Cisticercose/tratamento farmacológico , Sarcoma de Kaposi/parasitologia , Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Síndrome de Imunodeficiência Adquirida/complicações , Síndrome de Imunodeficiência Adquirida/tratamento farmacológico , Albendazol/uso terapêutico , Animais , Anticestoides/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Pré-Escolar , Cisticercose/etiologia , Humanos , Hospedeiro Imunocomprometido , Masculino , Praziquantel/uso terapêutico , Sarcoma de Kaposi/tratamento farmacológico , Tela Subcutânea/parasitologia , Tela Subcutânea/patologia , Taenia solium/patogenicidade , Tanzânia
16.
BMC Infect Dis ; 20(1): 245, 2020 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-32216747

RESUMO

BACKGROUND: In resource limited settings, Tuberculosis (TB) is a major cause of morbidity and mortality among patients on antiretroviral treatment. Ethiopia is one of the 30 high TB burden countries. TB causes burden in healthcare system and challenge the effectiveness of HIV care. This study was to assess incidence and predictors of Tuberculosis among adults on antiretroviral therapy at Debre Markos Referral Hospital, Northwest Ethiopia, 2019. METHODS: Institution based retrospective follow up study was conducted among adults on ART newly enrolled from 2014 to 2018 at Debre Markos Referral Hospital. Simple random sampling technique was used to select patients chart. Data was entered to EPI- INFO version 7.2.2.6 and analyzed using Stata 14.0. Tuberculosis incidence rate was computed and described using frequency tables. Both bivariable and multivariable Cox proportional hazard models was fitted to identify predictors of TB. RESULTS: Out of the 536 patients chart reviewed, 494 patient records were included in the analysis. A total of 62 patients developed new TB cases during the follow up period of 1000.22 Person Years (PY); which gives an overall incidence rate of 6.19 cases per 100 PY (95% CI: 4.83-7.95). The highest rate was seen within the first year of follow up. After adjustment base line Hemoglobin < 10 g/dl (AHR = 5.25; 95% CI: 2.52-10.95), ambulatory/bedridden patients at enrolment (AHR = 2.31; 95% CI: 1.13-4.73), having fair or poor ART adherence (AHR = 3.22; 95% CI: 1.64-6.31) were associated with increased risk of tuberculosis whereas taking Isoniazid Preventive Therapy (IPT) (AHR = 0.33; 95% CI: 0.12-0.85) were protective factors of TB occurrence. CONCLUSION: TB incidence was high among adults on ART especially in the first year of enrollment to ART. Low hemoglobin level, ambulatory or bedridden functional status, non-adherence to ART and IPT usage status were found to be independent predictors. Hence, continuous follow up for ART adherence and provision of IPT has a great importance to reduce the risk of TB.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Antirretrovirais/uso terapêutico , Tuberculose/epidemiologia , Infecções Oportunistas Relacionadas com a AIDS/virologia , Adolescente , Adulto , Antirretrovirais/efeitos adversos , Antituberculosos/uso terapêutico , Intervalo Livre de Doença , Etiópia/epidemiologia , Feminino , Seguimentos , HIV/isolamento & purificação , Humanos , Incidência , Isoniazida/uso terapêutico , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/isolamento & purificação , Prognóstico , Modelos de Riscos Proporcionais , Encaminhamento e Consulta , Estudos Retrospectivos , Tuberculose/microbiologia , Tuberculose/prevenção & controle , Adulto Jovem
17.
Lancet ; 395(10231): 1195-1207, 2020 04 11.
Artigo em Inglês | MEDLINE | ID: mdl-32145827

RESUMO

BACKGROUND: Optimal treatment regimens for AIDS-associated Kaposi sarcoma, a frequent contributor to morbidity and mortality among people with HIV, have not been systematically evaluated in low-income and middle-income countries, where the disease is most common. In this study, we aimed to investigate optimal treatment strategies for advanced stage disease in areas of high prevalence and limited resources. METHODS: In this open-label, non-inferiority trial, we enrolled people with HIV and advanced stage AIDS-associated Kaposi sarcoma attending 11 AIDS Clinical Trials Group sites in Brazil, Kenya, Malawi, South Africa, Uganda, and Zimbabwe. Eligible participants were randomly assigned (1:1:1) with a centralised computer system to receive either intravenous bleomycin and vincristine or oral etoposide (the investigational arms), or intravenous paclitaxel (the control arm), together with antiretroviral therapy (ART; combined efavirenz, tenofovir disoproxil fumarate, and emtricitabine). The primary outcome was progression-free survival (PFS) at week 48, using a 15% non-inferiority margin to compare the investigational groups against the active control group. Safety was assessed in all eligible treated study participants. The study was registered with ClinicalTrials.gov, NCT01435018. FINDINGS: 334 participants were enrolled between Oct 1, 2013, and March 8, 2018, when the study was closed early due to inferiority of the bleomycin and vincristine plus ART arm, as per the recommendations of the Data and Safety Monitoring Board (DSMB). The etoposide plus ART arm also closed due to inferiority in March, 2016, following a DSMB recommendation. Week-48 PFS rates were higher in the paclitaxel plus ART arm than in both investigational arms. The absolute differences in PFS were -30% (95% CI -52 to -8) for the comparison of paclitaxel plus ART (week 48 PFS 50%, 32 to 67; n=59) and etoposide plus ART (20%, 6 to 33; n=59), and -20% (-33% to -7%) for the comparison of paclitaxel plus ART (64%, 55 to 73; n=138) and bleomycin and vincristine plus ART (44%, 35 to 53; n=132). Both CIs overlapped the non-inferiority margin. The most common adverse events, in 329 eligible participants who began treatment, were neutropenia (48 [15%]), low serum albumin (33 [10%]), weight loss (29 [9%]), and anaemia (28 [9%]), occurring at similar frequency across treatment arms. INTERPRETATION: Non-inferiority of either investigational intervention was not shown, with paclitaxel plus ART showing superiority to both oral etoposide plus ART and bleomycin and vincristine plus ART, supporting its use in treating advanced AIDS-associated Kaposi sarcoma in resource-limited settings. FUNDING: US National Institute of Allergy and Infectious Diseases and National Cancer Institute, National Institutes of Health.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Antibióticos Antineoplásicos/efeitos adversos , Antineoplásicos Fitogênicos/efeitos adversos , Bleomicina/efeitos adversos , Sarcoma de Kaposi/tratamento farmacológico , Vincristina/efeitos adversos , Infecções Oportunistas Relacionadas com a AIDS/mortalidade , Adulto , África , Fármacos Anti-HIV/administração & dosagem , Antibióticos Antineoplásicos/administração & dosagem , Antineoplásicos Fitogênicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica , Terapia Antirretroviral de Alta Atividade/métodos , Bleomicina/administração & dosagem , Países em Desenvolvimento , Quimioterapia Combinada , Etoposídeo/administração & dosagem , Etoposídeo/efeitos adversos , Feminino , Humanos , Masculino , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Intervalo Livre de Progressão , Sarcoma de Kaposi/mortalidade , Vincristina/administração & dosagem
18.
BMC Infect Dis ; 20(1): 141, 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32059703

RESUMO

BACKGROUND: The global annual estimate for cryptococcal disease-related deaths exceeds 180,000, with three fourth occurring in sub-Saharan Africa. The World Health Organization (WHO) recommends cryptococcal antigen (CrAg) screening in all HIV patients with CD4 count < 100/µl. As there is no previous published study on the burden and impact of cryptococcal disease in Sierra Leone, research is needed to inform public health policies. We aimed to establish the seroprevalence and mortality of cryptococcal disease in adults with advanced HIV attending an urban tertiary hospital in Sierra Leone. METHODS: A prospective cohort study design was used to screen consecutive adult (18 years or older) HIV patients at Connaught Hospital in Freetown, Sierra Leone with CD4 count below 100 cells/mm3 from January to April 2018. Participants received a blood CrAg lateral flow assay (IMMY, Oklahoma, USA). All participants with a positive serum CrAg had lumbar puncture and cerebrospinal fluid (CSF) CrAg assay, and those with cryptococcal diseases had fluconazole monotherapy with 8 weeks followed up. Data were entered into Excel and analysed in Stata version 13.0. Proportions, median and interquartile ranges were used to summarise the data. Fisher's exact test was used to compare categorical variables. RESULTS: A total of 170 patients, with median age of 36 (IQR 30-43) and median CD4 count of 45 cells/mm3 (IQR 23-63) were screened. At the time of enrolment, 54% were inpatients, 51% were newly diagnosed with HIV, and 56% were either ART-naïve or newly initiated (≤ 30 days). Eight participants had a positive blood CrAg, giving a prevalence of 4.7% (95% CI: 2.4-9.2%). Of those with a positive CrAg, CSF CrAg was positive in five (62.5%). Five (62.5%) CrAg-positive participants died within the first month, while the remaining three were alive and established on ART at 8 weeks. CONCLUSION: A substantial prevalence of cryptococcal antigenaemia and poor outcome of cryptococcal disease were demonstrated in our study. The high mortality suggests a need for the HIV programme to formulate and implement policies on screening and pre-emptive fluconazole therapy for all adults with advanced HIV in Sierra Leone, and advocate for affordable access to effective antifungal therapies.


Assuntos
Antígenos de Fungos/sangue , Criptococose/epidemiologia , Infecções por HIV/microbiologia , Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Infecções Oportunistas Relacionadas com a AIDS/mortalidade , Adulto , Antifúngicos/uso terapêutico , Estudos Transversais , Criptococose/diagnóstico , Criptococose/tratamento farmacológico , Criptococose/mortalidade , Cryptococcus , Feminino , Fluconazol/uso terapêutico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/mortalidade , Humanos , Pacientes Internados/estatística & dados numéricos , Masculino , Meningite Criptocócica/diagnóstico , Meningite Criptocócica/tratamento farmacológico , Meningite Criptocócica/epidemiologia , Prevalência , Estudos Prospectivos , Estudos Soroepidemiológicos , Serra Leoa/epidemiologia , Centros de Atenção Terciária/estatística & dados numéricos
19.
BMC Infect Dis ; 20(1): 164, 2020 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-32087682

RESUMO

BACKGROUND: Multidrug resistant tuberculosis (MDR-TB) remains a serious public health problem with poor treatment outcomes. Predictors of poor outcomes vary in different regions. Vietnam is among the top 30 high burden of MDR-TB countries. We describe demographic characteristics and identify risk factors for poor outcome among patients with MDR-TB in Ho Chi Minh City (HCMC), the most populous city in Vietnam. METHODS: This retrospective study included 2266 patients who initiated MDR-TB treatment between 2011 and 2015 in HCMC. Treatment outcomes were available for 2240 patients. Data was collected from standardized paper-based treatment cards and electronic records. A Kruskal Wallis test was used to assess changes in median age and body mass index (BMI) over time, and a Wilcoxon test was used to compare the median BMI of patients with and without diabetes mellitus. Chi squared test was used to compare categorical variables. Multivariate logistic regression with multiple imputation for missing data was used to identify risk factors for poor outcomes. Statistical analysis was performed using R program. RESULTS: Among 2266 eligible cases, 60.2% had failed on a category I or II treatment regimen, 57.7% were underweight, 30.2% had diabetes mellitus and 9.6% were HIV positive. The notification rate increased 24.7% from 2011 to 2015. The treatment success rate was 73.3%. Risk factors for poor treatment outcome included HIV co-infection (adjusted odds ratio (aOR): 2.94), advanced age (aOR: 1.45 for every increase of 5 years for patients 60 years or older), having history of MDR-TB treatment (aOR: 5.53), sputum smear grade scanty or 1+ (aOR: 1.47), smear grade 2+ or 3+ (aOR: 2.06), low BMI (aOR: 0.83 for every increase of 1 kg/m2 of BMI for patients with BMI < 21). CONCLUSION: The number of patients diagnosed with MDR-TB in HCMC increased by almost a quarter between 2011 and 2015. Patients with HIV, high smear grade, malnutrition or a history of previous MDR-TB treatment are at greatest risk of poor treatment outcome.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Mycobacterium tuberculosis/genética , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Adulto , Fatores Etários , Coinfecção , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Feminino , Seguimentos , Humanos , Incidência , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Mycobacterium tuberculosis/isolamento & purificação , Estudos Retrospectivos , Fatores de Risco , Escarro/microbiologia , Resultado do Tratamento , Vietnã/epidemiologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA