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1.
Microb Genom ; 7(11)2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34845980

RESUMO

Mycobacterium abscessus comprises three subspecies: M. abscessus subsp. abscessus, M. abscessus subsp. bolletii, and M. abscessus subsp. massiliense. These closely related strains are typically multi-drug-resistant and can cause difficult-to-treat infections. Dominant clusters of isolates with increased pathogenic potential have been demonstrated in pulmonary infections in the global cystic fibrosis (CF) population. An investigation was performed on isolates cultured from an Asian, predominantly non-CF population to explore the phylogenomic relationships within our population and compare it to global M. abscessus isolates. Whole-genome-sequencing was performed on M. abscessus isolates between 2017 and 2019. Bioinformatic analysis was performed to determine multi-locus-sequence-type, to establish the phylogenetic relationships between isolates, and to identify virulence and resistance determinants in these isolates. A total of 210 isolates were included, of which 68.5 % (144/210) were respiratory samples. These isolates consisted of 140 (66.6 %) M. abscessus subsp. massiliense, 67 (31.9 %) M. abscessus subsp. abscessus, and three (1.4 %) M. abscessus subsp. bolletii. Dominant sequence-types in our population were similar to those of global CF isolates, but SNP differences in our population were comparatively wider despite the isolates being from the same geographical region. ESX (ESAT-6 secretory) cluster three appeared to occur most commonly in ST4 and ST6 M. abscessus subsp. massiliense, but other virulence factors did not demonstrate an association with isolate subspecies or sample source. We demonstrate that although similar predominant sequence-types are seen in our patient population, cross-transmission is absent. The risk of patient-to-patient transmission appears to be largely limited to the vulnerable CF population, indicating infection from environmental sources remains more common than human-to-human transmission. Resistance and virulence factors are largely consistent across the subspecies with the exception of clarithromycin susceptibility and ESX-3.


Assuntos
Fibrose Cística , Mycobacterium abscessus , Claritromicina , Humanos , Epidemiologia Molecular , Mycobacterium abscessus/genética , Filogenia
2.
PLoS One ; 16(6): e0252320, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34077481

RESUMO

BACKGROUND: While the use of combination antiretroviral therapy (cART) has conferred significant reduction in morbidity and mortality, there are growing concerns about the metabolic complications of antiretroviral regimens in HIV-infected patients. The aim of this study was to estimate the prevalence of metabolic syndrome (MetS) among people living with HIV (PLHIV) in Singapore. METHODS: We conducted a retrospective study using the clinical database maintained by the Clinical HIV Programme at the National Centre for Infectious Diseases, Singapore. Treatment-experienced PLHIV on follow-up during 2015-2017 were included. MetS was defined as having three or more of the following five abnormalities: hypertriglyceridemia, HDL hypocholesterolemia, hypertension, obesity, and diabetes. RESULTS: A total of 2,231 PLHIV were included in this study. 93.9% were men, and the median age at latest follow-up was 48 years. The median duration of HIV infection and duration of exposure to cART was 6.8 years and 5.7 years, respectively. All had been exposed to nucleoside reverse transcriptase inhibitors (NRTIs) as the first line of treatment, 93.9% to non-NRTIs, 28.6% to protease inhibitors (PIs) and 12.8% to integrase strand transfer inhibitors. The most common metabolic abnormality among PLHIV was HDL hypocholesterolemia (60.2%) followed by hypertriglyceridemia (45.5%). Of all the 2,231 individuals, 68.8% had at least one component of MetS. The overall prevalence of MetS was 23.6% (95% confidence interval 21.9%-25.4%). Of the 526 with MetS, the most common combination was HDL hypocholesterolemia, hypertriglyceridemia and hypertension (51.0%), followed by HDL hypocholesterolemia, hypertriglyceridemia, hypertension and diabetes (25.1%). Compared with PLHIV without MetS, a significantly higher proportion of those with MetS were ever on protease inhibitors (33.5% vs. 27.1%). CONCLUSION: MetS is common in PLHIV. In view of the progressive aging of HIV-infected population and long-term use of cART, regular monitoring for metabolic abnormalities, surveillance of drug effects and behavioural interventions are needed to optimize management and prevention of metabolic disorders in PLHIV.


Assuntos
Fármacos Anti-HIV/efeitos adversos , Infecções por HIV/tratamento farmacológico , HIV/isolamento & purificação , Síndrome Metabólica/epidemiologia , Adolescente , Adulto , Idoso , Feminino , Seguimentos , HIV/efeitos dos fármacos , Infecções por HIV/virologia , Humanos , Masculino , Síndrome Metabólica/induzido quimicamente , Síndrome Metabólica/patologia , Pessoa de Meia-Idade , Prevalência , Prognóstico , Estudos Retrospectivos , Singapura/epidemiologia , Adulto Jovem
3.
Clin Infect Dis ; 71(15): 786-792, 2020 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-32211755

RESUMO

BACKGROUND: Rapid identification of COVID-19 cases, which is crucial to outbreak containment efforts, is challenging due to the lack of pathognomonic symptoms and in settings with limited capacity for specialized nucleic acid-based reverse transcription polymerase chain reaction (PCR) testing. METHODS: This retrospective case-control study involves subjects (7-98 years) presenting at the designated national outbreak screening center and tertiary care hospital in Singapore for SARS-CoV-2 testing from 26 January to 16 February 2020. COVID-19 status was confirmed by PCR testing of sputum, nasopharyngeal swabs, or throat swabs. Demographic, clinical, laboratory, and exposure-risk variables ascertainable at presentation were analyzed to develop an algorithm for estimating the risk of COVID-19. Model development used Akaike's information criterion in a stepwise fashion to build logistic regression models, which were then translated into prediction scores. Performance was measured using receiver operating characteristic curves, adjusting for overconfidence using leave-one-out cross-validation. RESULTS: The study population included 788 subjects, of whom 54 (6.9%) were SARS-CoV-2 positive and 734 (93.1%) were SARS-CoV-2 negative. The median age was 34 years, and 407 (51.7%) were female. Using leave-one-out cross-validation, all the models incorporating clinical tests (models 1, 2, and 3) performed well with areas under the receiver operating characteristic curve (AUCs) of 0.91, 0.88, and 0.88, respectively. In comparison, model 4 had an AUC of 0.65. CONCLUSIONS: Rapidly ascertainable clinical and laboratory data could identify individuals at high risk of COVID-19 and enable prioritization of PCR testing and containment efforts. Basic laboratory test results were crucial to prediction models.


Assuntos
Betacoronavirus/genética , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19 , Teste para COVID-19 , Estudos de Casos e Controles , Criança , Técnicas de Laboratório Clínico , Infecções por Coronavirus/virologia , Testes Diagnósticos de Rotina/métodos , Feminino , Humanos , Masculino , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/virologia , Reação em Cadeia da Polimerase/métodos , Estudos Retrospectivos , SARS-CoV-2 , Singapura/epidemiologia , Escarro/virologia , Adulto Jovem
4.
Angew Chem Int Ed Engl ; 59(17): 6819-6826, 2020 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-32011781

RESUMO

Carbapenem-resistant Gram-negative bacteria (GNB) are heading the list of pathogens for which antibiotics are the most critically needed. Many antibiotics are either unable to penetrate the outer-membrane or are excluded by efflux mechanisms. Here, we report a cationic block ß-peptide (PAS8-b-PDM12) that reverses intrinsic antibiotic resistance in GNB by two distinct mechanisms of action. PAS8-b-PDM12 does not only compromise the integrity of the bacterial outer-membrane, it also deactivates efflux pump systems by dissipating the transmembrane electrochemical potential. As a result, PAS8-b-PDM12 sensitizes carbapenem- and colistin-resistant GNB to multiple antibiotics in vitro and in vivo. The ß-peptide allows the perfect alternation of cationic versus hydrophobic side chains, representing a significant improvement over previous antimicrobial α-peptides sensitizing agents. Together, our results indicate that it is technically possible for a single adjuvant to reverse innate antibiotic resistance in all pathogenic GNB of the ESKAPE group, including those resistant to last resort antibiotics.


Assuntos
Antibacterianos/farmacologia , Bactérias Gram-Negativas/efeitos dos fármacos , Peptídeos/química , Peptídeos/farmacologia , Carbapenêmicos/farmacologia , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Glicosilação , Testes de Sensibilidade Microbiana , Conformação Proteica em Folha beta
5.
Antivir Ther ; 24(4): 271-279, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30833516

RESUMO

BACKGROUND: We aimed to project the 10-year future incidence of cardiovascular disease (CVD) and model several intervention scenarios based on a multi-site Asian HIV-positive cohort. METHODS: Analyses were based on patients recruited to the TREAT Asia HIV Observational Database (TAHOD), consisting of 21 sites in 12 countries. Patients on triple antiretroviral therapy (ART) were included if they were alive, without previous CVD, and had data on CVD risk factors. Annual new CVD events for 2019-2028 were estimated with the D:A:D equation, accounting for age- and sex-adjusted mortality. Modelled intervention scenarios were treatment of high total cholesterol, low high-density lipoprotein cholesterol (HDL) or high blood pressure, abacavir or lopinavir substitution, and smoking cessation. RESULTS: Of 3,703 included patients, 69% were male, median age was 46 (IQR 40-53) years and median time since ART initiation was 9.8 years (IQR 7.5-14.1). Cohort incidence rates of CVD were projected to increase from 730 per 100,000 person-years (pys) in 2019 to 1,432 per 100,000 pys in 2028. In the modelled intervention scenarios, most events can be avoided by smoking cessation, abacavir substitution, lopinavir substitution, decreasing total cholesterol, treating high blood pressure and increasing HDL. CONCLUSIONS: Our projections suggest a doubling of CVD incidence rates in Asian HIV-positive adults in our cohort. An increase in CVD can be expected in any ageing population, however, according to our models, this can be close to averted by interventions. Thus, there is an urgent need for risk screening and integration of HIV and CVD programmes to reduce the future CVD burden.


Assuntos
Doenças Cardiovasculares/epidemiologia , Infecções por HIV/epidemiologia , Adulto , Algoritmos , Terapia Antirretroviral de Alta Atividade , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/mortalidade , Comorbidade , Bases de Dados Factuais , Feminino , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Modelos Teóricos , Prognóstico
6.
J Int AIDS Soc ; 22(2): e25228, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30803162

RESUMO

INTRODUCTION: Multiple comorbidities among HIV-positive individuals may increase the potential for polypharmacy causing drug-to-drug interactions and older individuals with comorbidities, particularly those with cognitive impairment, may have difficulty in adhering to complex medications. However, the effects of age-associated comorbidities on the treatment outcomes of combination antiretroviral therapy (cART) are not well known. In this study, we investigated the effects of age-associated comorbidities on therapeutic outcomes of cART in HIV-positive adults in Asian countries. METHODS: Patients enrolled in the TREAT Asia HIV Observational Database cohort and on cART for more than six months were analysed. Comorbidities included hypertension, diabetes, dyslipidaemia and impaired renal function. Treatment outcomes of patients ≥50 years of age with comorbidities were compared with those <50 years and those ≥50 years without comorbidities. We analysed 5411 patients with virological failure and 5621 with immunologic failure. Our failure outcomes were defined to be in-line with the World Health Organization 2016 guidelines. Cox regression analysis was used to analyse time to first virological and immunological failure. RESULTS: The incidence of virologic failure was 7.72/100 person-years. Virological failure was less likely in patients with better adherence and higher CD4 count at cART initiation. Those acquiring HIV through intravenous drug use were more likely to have virological failure compared to those infected through heterosexual contact. On univariate analysis, patients aged <50 years without comorbidities were more likely to experience virological failure than those aged ≥50 years with comorbidities (hazard ratio 1.75, 95% confidence interval (CI) 1.31 to 2.33, p < 0.001). However, the multivariate model showed that age-related comorbidities were not significant factors for virological failure (hazard ratio 1.31, 95% CI 0.98 to 1.74, p = 0.07). There were 391 immunological failures, with an incidence of 2.75/100 person-years. On multivariate analysis, those aged <50 years without comorbidities (p = 0.025) and age <50 years with comorbidities (p = 0.001) were less likely to develop immunological failure compared to those aged ≥50 years with comorbidities. CONCLUSIONS: In our Asia regional cohort, age-associated comorbidities did not affect virologic outcomes of cART. Among those with comorbidities, patients <50 years old showed a better CD4 response.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Adulto , Fatores Etários , Idoso , Antirretrovirais/uso terapêutico , Ásia/epidemiologia , Contagem de Linfócito CD4 , Comorbidade , Bases de Dados Factuais , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento , Adulto Jovem
7.
J Acquir Immune Defic Syndr ; 80(3): 301-307, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30531303

RESUMO

BACKGROUND: Hematological malignancies have continued to be highly prevalent among people living with HIV (PLHIV). This study assessed the occurrence of, risk factors for, and outcomes of hematological and nonhematological malignancies in PLHIV in Asia. METHODS: Incidence of malignancy after cohort enrollment was evaluated. Factors associated with development of hematological and nonhematological malignancy were analyzed using competing risk regression and survival time using Kaplan-Meier. RESULTS: Of 7455 patients, 107 patients (1%) developed a malignancy: 34 (0.5%) hematological [0.08 per 100 person-years (/100PY)] and 73 (1%) nonhematological (0.17/100PY). Of the hematological malignancies, non-Hodgkin lymphoma was predominant (n = 26, 76%): immunoblastic (n = 6, 18%), Burkitt (n = 5, 15%), diffuse large B-cell (n = 5, 15%), and unspecified (n = 10, 30%). Others include central nervous system lymphoma (n = 7, 21%) and myelodysplastic syndrome (n = 1, 3%). Nonhematological malignancies were mostly Kaposi sarcoma (n = 12, 16%) and cervical cancer (n = 10, 14%). Risk factors for hematological malignancy included age >50 vs. ≤30 years [subhazard ratio (SHR) = 6.48, 95% confidence interval (CI): 1.79 to 23.43] and being from a high-income vs. a lower-middle-income country (SHR = 3.97, 95% CI: 1.45 to 10.84). Risk was reduced with CD4 351-500 cells/µL (SHR = 0.20, 95% CI: 0.05 to 0.74) and CD4 >500 cells/µL (SHR = 0.14, 95% CI: 0.04 to 0.78), compared to CD4 ≤200 cells/µL. Similar risk factors were seen for nonhematological malignancy, with prior AIDS diagnosis showing a weak association. Patients diagnosed with a hematological malignancy had shorter survival time compared to patients diagnosed with a nonhematological malignancy. CONCLUSIONS: Nonhematological malignancies were common but non-Hodgkin lymphoma was more predominant in our cohort. PLHIV from high-income countries were more likely to be diagnosed, indicating a potential underdiagnosis of cancer in low-income settings.


Assuntos
Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Neoplasias/complicações , Neoplasias/epidemiologia , Adulto , Ásia/epidemiologia , Contagem de Linfócito CD4 , Estudos de Coortes , Bases de Dados Factuais , Humanos , Análise Multivariada , Fatores de Risco , Análise de Sobrevida
8.
Pharmacoepidemiol Drug Saf ; 27(11): 1209-1216, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30246898

RESUMO

PURPOSE: Renal disease is common among people living with human immunodeficiency virus (HIV). However, there is limited information on the incidence and risk factors associated with renal dysfunction among this population in Asia. METHODS: We used data from the TREAT Asia HIV Observational Database. Patients were included if they started antiretroviral therapy during or after 2003, had a serum creatinine measurement at antiretroviral therapy initiation (baseline), and had at least 2 follow-up creatinine measurements taken ≥3 months apart. Patients with a baseline estimated glomerular filtration rate (eGFR) ≤60 mL/min/1.73 m2 were excluded. Chronic kidney disease was defined as 2 consecutive eGFR values ≤60 mL/min/1.73 m2 taken ≥3 months apart. Generalized estimating equations were used to identify factors associated with eGFR change. Competing risk regression adjusted for study site, age and sex, and cumulative incidence plots were used to evaluate factors associated with chronic kidney disease (CKD). RESULTS: Of 2547 patients eligible for this analysis, tenofovir was being used by 703 (27.6%) at baseline. Tenofovir use, high baseline eGFR, advanced HIV disease stage, and low nadir CD4 were associated with a decrease in eGFR during follow-up. Chronic kidney disease occurred at a rate of 3.4 per 1000 patient/years. Factors associated with CKD were tenofovir use, old age, low baseline eGFR, low nadir CD4, and protease inhibitor use. CONCLUSIONS: There is an urgent need to enhance renal monitoring and management capacity among at-risk groups in Asia and improve access to less nephrotoxic antiretrovirals.


Assuntos
Fármacos Anti-HIV/efeitos adversos , Taxa de Filtração Glomerular/efeitos dos fármacos , Infecções por HIV/tratamento farmacológico , Rim/efeitos dos fármacos , Insuficiência Renal Crônica/epidemiologia , Adulto , Fatores Etários , Fármacos Anti-HIV/administração & dosagem , Ásia/epidemiologia , Creatinina/sangue , Feminino , Seguimentos , Taxa de Filtração Glomerular/fisiologia , Humanos , Incidência , Rim/fisiopatologia , Masculino , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/induzido quimicamente , Insuficiência Renal Crônica/fisiopatologia , Fatores de Risco , Tenofovir/administração & dosagem , Tenofovir/efeitos adversos , Fatores de Tempo
9.
Artigo em Inglês | MEDLINE | ID: mdl-29644052

RESUMO

Background: In May 2015, we noticed an increase in carbapenem-resistant Acinetobacter baumannii (CRAB) infections in the Medical Intensive Care Unit (MICU). To investigate this, we studied the extent of environmental contamination and subsequent onward clonal transmission of CRAB. Methods: We conducted a one-day point prevalence screening (PPS) of the patients and environment in the MICU. We screened patients using endotracheal tube aspirates and swabs from nares, axillae, groin, rectum, wounds, and exit sites of drains. We collected environmental samples from patients' rooms and environment outside the patients' rooms. CRAB isolates from the PPS and clinical samples over the subsequent one month were studied for genetic relatedness by whole genome sequencing (WGS). Results: We collected 34 samples from seven patients and 244 samples from the environment. On the day of PPS, we identified 8 CRAB carriers: 3 who screened positive and 5 previously known clinical infections. We detected environmental contamination in nearly two-thirds of the rooms housing patients with CRAB. WGS demonstrated genetic clustering of isolates within rooms but not across rooms. We analysed 4 CRAB isolates from clinical samples following the PPS. One genetically-related CRAB was identified in the respiratory sample of a patient with nosocomial pneumonia, who was admitted to the MICU five days after the PPS. Conclusion: The extensive environmental colonization of CRAB by patients highlights the importance of environmental hygiene. The transmission dynamics of CRAB needs further investigation.


Assuntos
Infecções por Acinetobacter/epidemiologia , Infecções por Acinetobacter/transmissão , Acinetobacter baumannii/efeitos dos fármacos , Antibacterianos/farmacologia , Carbapenêmicos/farmacologia , Infecção Hospitalar/epidemiologia , Farmacorresistência Bacteriana Múltipla/fisiologia , Unidades de Terapia Intensiva/estatística & dados numéricos , Infecções por Acinetobacter/microbiologia , Acinetobacter baumannii/classificação , Acinetobacter baumannii/isolamento & purificação , Feminino , Humanos , Higiene , Intubação/efeitos adversos , Masculino , Programas de Rastreamento , Testes de Sensibilidade Microbiana
10.
Clin Infect Dis ; 64(suppl_2): S68-S75, 2017 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-28475792

RESUMO

BACKGROUND: Since 2010, the incidence of carbapenem-resistant Enterobacteriaceae (CRE) has been increasing in Singapore. We analyzed the clinical and molecular epidemiology of CRE among adult inpatients in Singapore. METHODS: Quarterly incidence of unique subjects (per 100000 patient-days) with positive clinical and surveillance cultures for CRE were estimated based on mandatory data submitted to the National Public Health Laboratory by public hospitals between 2010 and 2015. CRE-positive adult inpatients were prospectively recruited from 6 public sector hospitals between December 2013 and April 2015. Subjects answered a standardized epidemiologic questionnaire and provided samples for this study. Further clinical information was extracted from subjects' electronic medical records. Whole-genome sequencing was performed on study isolates to determine transmission clusters. RESULTS: Incidence of CRE clinical cultures among adult inpatients plateaued from 2013 (range: 7.73 to 10.32 per 100000 patient-days) following an initial increase between 2010 and end-2012. We prospectively recruited 249 subjects. Their median age was 65 years, 108 (43%) were female, and 161 (64.7%) had carbapenemase-producing Enterobacteriaceae (CPE). On multivariate analysis, prior carbapenem exposure (OR: 3.23; 95% CI: 1.67-6.25) and hematological malignancies (OR: 2.85; 95% CI: 1.10-7.41) were associated with non-carbapenemase-producing CRE (NCPE) (n = 88) compared with CPE (n = 161) subjects. Among 430 CRE isolates from the 249 subjects, 307(71.3%) were CPE, of which 154(50.2%) were blaKPC-positive, 97(31.6%) blaNDM-positive, and 42 (13.7%) blaOXA-positive. Klebsiella pneumoniae (n = 180, 41.9%), Escherichia coli (n = 129, 30.0%) and Enterobacter cloacae (n = 62, 14.4%) were the main Enterobacteriaceae species. WGS (n = 206) revealed diverse bacterial strain type (STs). The predominant blaKPC-positive plasmid was pHS102707 (n = 62, 55.4%) and the predominant blaNDM-positive plasmid was pNDM-ECS01 (n = 46, 48.9%). Five transmission clusters involving 13 subjects were detected. CONCLUSIONS: Clinical CRE trend among adult inpatients showed stabilization following a rapid rise since introduction in 2010 potentially due to infection prevention measures and antimicrobial stewardship. More work is needed on understanding CPE transmission dynamics.


Assuntos
Enterobacteriáceas Resistentes a Carbapenêmicos/genética , Infecção Hospitalar/epidemiologia , Infecções por Enterobacteriaceae/epidemiologia , Pacientes Internados , Adulto , Idoso , Antibacterianos/uso terapêutico , Enterobacteriáceas Resistentes a Carbapenêmicos/efeitos dos fármacos , Enterobacteriáceas Resistentes a Carbapenêmicos/isolamento & purificação , Carbapenêmicos/farmacologia , Carbapenêmicos/uso terapêutico , DNA Bacteriano/genética , Registros Eletrônicos de Saúde , Enterobacter cloacae/genética , Enterobacter cloacae/isolamento & purificação , Infecções por Enterobacteriaceae/microbiologia , Infecções por Enterobacteriaceae/transmissão , Escherichia coli/genética , Escherichia coli/isolamento & purificação , Infecções por Escherichia coli/epidemiologia , Feminino , Genoma Bacteriano , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Incidência , Infecções por Klebsiella/epidemiologia , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/isolamento & purificação , Masculino , Inquéritos e Questionários , Adulto Jovem , Resistência beta-Lactâmica , beta-Lactamases/biossíntese , beta-Lactamases/genética
12.
PLoS One ; 9(9): e106525, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25184314

RESUMO

BACKGROUND: Antiretroviral therapy (ART) has evolved rapidly since its beginnings. This analysis describes trends in first-line ART use in Asia and their impact on treatment outcomes. METHODS: Patients in the TREAT Asia HIV Observational Database receiving first-line ART for ≥ 6 months were included. Predictors of treatment failure and treatment modification were assessed. RESULTS: Data from 4662 eligible patients was analysed. Patients started ART in 2003-2006 (n = 1419), 2007-2010 (n = 2690) and 2011-2013 (n = 553). During the observation period, tenofovir, zidovudine and abacavir use largely replaced stavudine. Stavudine was prescribed to 5.8% of ART starters in 2012/13. Efavirenz use increased at the expense of nevirapine, although both continue to be used extensively (47.5% and 34.5% of patients in 2012/13, respectively). Protease inhibitor use dropped after 2004. The rate of treatment failure or modification declined over time (22.1 [95%CI 20.7-23.5] events per 100 patient/years in 2003-2006, 15.8 [14.9-16.8] in 2007-2010, and 11.6 [9.4-14.2] in 2011-2013). Adjustment for ART regimen had little impact on the temporal decline in treatment failure rates but substantially attenuated the temporal decline in rates of modification due to adverse event. In the final multivariate model, treatment modification due to adverse event was significantly predicted by earlier period of ART initiation (hazard ratio 0.52 [95%CI 0.33-0.81], p = 0.004 for 2011-2013 versus 2003-2006), older age (1.56 [1.19-2.04], p = 0.001 for ≥ 50 years versus <30 years), female sex (1.29 [1.11-1.50], p = 0.001 versus male), positive hepatitis C status (1.33 [1.06-1.66], p = 0.013 versus negative), and ART regimen (11.36 [6.28-20.54], p<0.001 for stavudine-based regimens versus tenofovir-based). CONCLUSIONS: The observed trends in first-line ART use in Asia reflect changes in drug availability, global treatment recommendations and prescriber preferences over the past decade. These changes have contributed to a declining rate of treatment modification due to adverse event, but not to reductions in treatment failure.


Assuntos
Terapia Antirretroviral de Alta Atividade/métodos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Infecções por HIV/tratamento farmacológico , Inibidores da Transcriptase Reversa/uso terapêutico , Adulto , Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Ásia , Didesoxinucleosídeos/uso terapêutico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/classificação , Feminino , HIV/efeitos dos fármacos , Infecções por HIV/patologia , Infecções por HIV/virologia , Humanos , Masculino , Nevirapina/uso terapêutico , Estavudina/uso terapêutico
13.
PLoS One ; 7(9): e45168, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23028822

RESUMO

BACKGROUND: The United States FDA approved an over-the-counter HIV self-test, to facilitate increased HIV testing and earlier linkage to care. We assessed the accuracy of self-testing by untrained participants compared to healthcare worker (HCW) testing, participants' ability to interpret sample results and user-acceptability of self-tests in Singapore. METHODOLOGY/PRINCIPAL FINDINGS: A cross-sectional study, involving 200 known HIV-positive patients and 794 unknown HIV status at-risk participants was conducted. Participants (all without prior self-test experience) performed self-testing guided solely by visual instructions, followed by HCW testing, both using the OraQuick ADVANCE Rapid HIV 1/2 Antibody Test, with both results interpreted by the HCW. To assess ability to interpret results, participants were provided 3 sample results (positive, negative, and invalid) to interpret. Of 192 participants who tested positive on HCW testing, self-testing was positive in 186 (96.9%), negative in 5 (2.6%), and invalid in 1 (0.5%). Of 794 participants who tested negative on HCW testing, self-testing was negative in 791 (99.6%), positive in 1 (0.1%), and invalid in 2 (0.3%). Excluding invalid tests, self-testing had sensitivity of 97.4% (95% CI 95.1% to 99.7%) and specificity of 99.9% (95% CI: 99.6% to 100%). When interpreting results, 96%, 93.1% and 95.2% correctly read the positive, negative and invalid respectively. There were no significant demographic predictors for false negative self-testing or wrongly interpreting positive or invalid sample results as negative. Eighty-seven percent would purchase the kit over-the-counter; 89% preferred to take HIV tests in private. 72.5% and 74.9% felt the need for pre- and post-test counseling respectively. Only 28% would pay at least USD15 for the test. CONCLUSIONS/SIGNIFICANCE: Self-testing was associated with high specificity, and a small but significant number of false negatives. Incorrectly identifying model results as invalid was a major reason for incorrect result interpretation. Survey responses were supportive of making self-testing available.


Assuntos
Sorodiagnóstico da AIDS/métodos , Autoavaliação Diagnóstica , Anticorpos Anti-HIV/sangue , Soropositividade para HIV/diagnóstico , HIV/química , Sorodiagnóstico da AIDS/estatística & dados numéricos , Adulto , Estudos Transversais , Reações Falso-Negativas , Feminino , Anticorpos Anti-HIV/imunologia , Soropositividade para HIV/sangue , Soropositividade para HIV/imunologia , Humanos , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Kit de Reagentes para Diagnóstico/estatística & dados numéricos , Sensibilidade e Especificidade , Singapura
14.
PLoS One ; 7(4): e34663, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22493708

RESUMO

INTRODUCTION: Since 2008, the Singapore Ministry of Health (MOH) has expanded HIV testing by increasing anonymous HIV test sites, as well as issuing a directive to hospitals to offer routine voluntary opt out inpatient HIV testing. We reviewed this program implemented at the end of 2008 at Tan Tock Seng Hospital (TTSH), the second largest acute care general hospital in Singapore. METHODS AND FINDINGS: From January 2009 to December 2010, all inpatients aged greater or equal than 21 years were screened for HIV unless they declined or were not eligible for screening. We reviewed the implementation of the Opt Out testing policy. There were a total of 93,211 admissions; 41,543 patients were included based on HIV screening program eligibility criteria. Among those included, 79% (n = 32,675) opted out of HIV screening. The overall acceptance rate was 21%. Majority of eligible patients who were tested (63%) were men. The mean age of tested patients was 52 years. The opt out rate was significantly higher among females (OR: 1.5, 95%CI: 1.4-1.6), aged >60 years (OR: 2.3, 95%CI: 2.2-2.4) and Chinese ethnicity (OR: 1.7, 95%CI:1.6-1.8). The false positive rate of the HIV screening test is 0.56%. The proportion of patients with HIV infection among those who underwent HIV screening is 0.18%. All 16 confirmed HIV patients were linked to care. CONCLUSION: The default opt-in rate of inpatient HIV testing was low at Tan Tock Seng Hospital, Singapore. Efforts to address individual HIV risk perception and campaigns against HIV stigma are needed to encourage more individuals to be tested for HIV.


Assuntos
Testes Anônimos/psicologia , Infecções por HIV/diagnóstico , Soropositividade para HIV/diagnóstico , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Adulto , Testes Anônimos/estatística & dados numéricos , Serviço Hospitalar de Emergência , Feminino , HIV/genética , Infecções por HIV/virologia , Soropositividade para HIV/virologia , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Fatores Sexuais , Singapura
15.
Ann Acad Med Singap ; 41(12): 571-6, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23303114

RESUMO

INTRODUCTION: Highly active antiretroviral therapy (HAART) has improved outcomes for individuals infected with human immunodeficiency virus (HIV). This study describes the causes of death in hospitalised HIV-positive patients from 2008 to 2010 in Tan Tock Seng Hospital, the national referral centre for HIV management in Singapore. MATERIALS AND METHODS: Data were retrospectively collected from HIV-positive patients who died in Tan Tock Seng Hospital from January 2008 to December 2010. RESULTS: Sixty-seven deaths occurred in the study period. A majority of patients died of non-acquired immune deficiency syndrome (AIDS)-defining illnesses (54.7%). The median CD4 count was 39.5 (range, 20.0 to 97.0), and 7 patients had HIV viral loads of <200 copies/mL. There were 27 deaths due to opportunistic infections, 27 due to non AIDS-defining infections, 4 due to non AIDS-associated malignancies. This study also describes 3 deaths due to cardiovascular events, and 1 due to hepatic failure. Patients who had virologic suppression were more likely to die from non AIDS-defining causes. CONCLUSION: Causes of death in HIV-positive patients have changed in the HAART era. More research is required to further understand and address barriers to testing and treatment to further improve outcomes in HIV/AIDS.


Assuntos
Soropositividade para HIV/mortalidade , Mortalidade Hospitalar/tendências , Hospitalização , Antirretrovirais/uso terapêutico , Contagem de Linfócito CD4 , Causas de Morte/tendências , Feminino , Soropositividade para HIV/tratamento farmacológico , Soropositividade para HIV/epidemiologia , Humanos , Masculino , Auditoria Médica , Pessoa de Meia-Idade , Estudos Retrospectivos , Singapura/epidemiologia
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