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1.
J Virol ; 96(16): e0058822, 2022 08 24.
Article in English | MEDLINE | ID: mdl-35916523

ABSTRACT

Co-infection with hepatitis B (HBV) and human immunodeficiency virus (HIV) increases overall and liver-related mortality. In order to identify interactions between these two viruses in vivo, full-length HIV proviruses were sequenced from a cohort of HIV-HBV co-infected participants and from a cohort of HIV mono-infected participants recruited from Bangkok, Thailand, both before the initiation of antiretroviral therapy (ART) and after at least 2 years of ART. The co-infected individuals were found to have higher levels of genetically-intact HIV proviruses than did mono-infected individuals pre-therapy. In these co-infected individuals, higher levels of genetically-intact HIV proviruses or proviral genetic-diversity were also associated with higher levels of sCD14 and CXCL10, suggesting that immune activation is linked to more genetically-intact HIV proviruses. Three years of ART decreased the overall level of HIV proviruses, with fewer genetically-intact proviruses being identified in co-infected versus mono-infected individuals. However, ART increased the frequency of certain genetic defects within proviruses and the expansion of identical HIV sequences. IMPORTANCE With the increased availability and efficacy of ART, co-morbidities are now one of the leading causes of death in HIV-positive individuals. One of these co-morbidities is co-infection with HBV. However, co-infections are still relatively understudied, especially in countries where such co-infections are endemic. Furthermore, these countries have different subtypes of HIV circulating than the commonly studied HIV subtype B. We believe that our study serves this understudied niche and provides a novel approach to investigating the impact of HBV co-infection on HIV infection. We examine co-infection at the molecular level in order to investigate indirect associations between the two viruses through their interactions with the immune system. We demonstrate that increased immune inflammation and activation in HBV co-infected individuals is associated with higher HIV viremia and an increased number of genetically-intact HIV proviruses in peripheral blood cells. This leads us to hypothesize that inflammation could be a driver in the increased mortality rate of HIV-HBV co-infected individuals.


Subject(s)
Coinfection , HIV Infections , Hepatitis B , Inflammation/virology , Coinfection/pathology , Coinfection/virology , DNA, Viral/genetics , HIV Infections/complications , HIV Infections/pathology , HIV Infections/virology , Hepatitis B/complications , Hepatitis B/pathology , Hepatitis B/virology , Hepatitis B virus/physiology , Humans , Proviruses/genetics , Thailand/epidemiology , Viremia/virology
2.
Med J Aust ; 218(8): 361-367, 2023 05 01.
Article in English | MEDLINE | ID: mdl-37032118

ABSTRACT

OBJECTIVES: To assess the mental health and wellbeing of health and aged care workers in Australia during the second and third years of the coronavirus disease 2019 (COVID-19) pandemic, overall and by occupation group. DESIGN, SETTING, PARTICIPANTS: Longitudinal cohort study of health and aged care workers (ambulance, hospitals, primary care, residential aged care) in Victoria: May-July 2021 (survey 1), October-December 2021 (survey 2), and May-June 2022 (survey 3). MAIN OUTCOME MEASURES: Proportions of respondents (adjusted for age, gender, socio-economic status) reporting moderate to severe symptoms of depression (Patient Health Questionnaire-9, PHQ-9), anxiety (Generalized Anxiety Disorder scale, GAD-7), or post-traumatic stress (Impact of Event Scale-6, IES-6), burnout (abbreviated Maslach Burnout Inventory, aMBI), or high optimism (10-point visual analogue scale); mean scores (adjusted for age, gender, socio-economic status) for wellbeing (Personal Wellbeing Index-Adult, PWI-A) and resilience (Connor Davidson Resilience Scale 2, CD-RISC-2). RESULTS: A total of 1667 people responded to at least one survey (survey 1, 989; survey 2, 1153; survey 3, 993; response rate, 3.3%). Overall, 1211 survey responses were from women (72.6%); most respondents were hospital workers (1289, 77.3%) or ambulance staff (315, 18.9%). The adjusted proportions of respondents who reported moderate to severe symptoms of depression (survey 1, 16.4%; survey 2, 22.6%; survey 3, 19.2%), anxiety (survey 1, 8.8%; survey 2, 16.0%; survey 3, 11.0%), or post-traumatic stress (survey 1, 14.6%; survey 2, 35.1%; survey 3, 14.9%) were each largest for survey 2. The adjusted proportions of participants who reported moderate to severe symptoms of burnout were higher in surveys 2 and 3 than in survey 1, and the proportions who reported high optimism were smaller in surveys 2 and 3 than in survey 1. Adjusted mean scores for wellbeing and resilience were similar at surveys 2 and 3 and lower than at survey 1. The magnitude but not the patterns of change differed by occupation group. CONCLUSION: Burnout was more frequently reported and mean wellbeing and resilience scores were lower in mid-2022 than in mid-2021 for Victorian health and aged care workers who participated in our study. Evidence-based mental health and wellbeing programs for workers in health care organisations are needed. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry: ACTRN12621000533897 (observational study; retrospective).


Subject(s)
Burnout, Professional , COVID-19 , Adult , Humans , Female , Aged , COVID-19/epidemiology , Mental Health , Longitudinal Studies , Retrospective Studies , Health Personnel/psychology , Anxiety , Surveys and Questionnaires , Burnout, Professional/psychology , Victoria/epidemiology , Depression/epidemiology
3.
Intern Med J ; 53(7): 1115-1120, 2023 07.
Article in English | MEDLINE | ID: mdl-37183656

ABSTRACT

BACKGROUND: Coronavirus disease (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with a heterogeneous presentation ranging from severe pneumonitis to asymptomatic infection. International studies have demonstrated the utility of respiratory care units (RCUs) to facilitate the delivery of non-invasive ventilation techniques to patients with COVID-19 pneumonitis. AIMS: This study aims to describe the patient characteristics, flow and outcomes of admissions to the Royal Melbourne Hospital (RMH) COVID-19 RCU (CRCU) during its initial period of operation. METHODS: Single-centre retrospective cohort study, all patients admitted to CRCU between 17 September and 10 December 2021 were included in this study. Patient demographics, including comorbidities and limitations of medical treatment, were analysed. Admission source and discharge destination were reviewed. Length of stay was recorded. Finally, in-hospital and CRCU mortality were analysed. RESULTS: Ninety-seven patients, comprising 111 admissions, occurred during the study period with median age of 65 years (48% female). Most patients were admitted from and discharged to the ward. Twenty patients died in hospital (21%), with age, 4C score, comorbidity and presence of obstructive lung disease predicting mortality (area under the curve (AUC) 0.85, P < 0.001). Mortality was significantly higher in those over 65 years of age compared to those under 65 (P < 0.001), or those deemed not for intubation compared to those for intubation (P = 0.0019). CONCLUSIONS: This study demonstrates the feasibility of operating a CRCU within an Australian tertiary healthcare setting.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Female , Aged , Child, Preschool , Male , COVID-19/therapy , Respiratory Care Units , Retrospective Studies , Australia/epidemiology , Intensive Care Units
4.
Ann Intern Med ; 175(5): JC51, 2022 05.
Article in English | MEDLINE | ID: mdl-35500262

ABSTRACT

SOURCE CITATION: Ali K, Azher T, Baqi M, et al. Remdesivir for the treatment of patients in hospital with COVID-19 in Canada: a randomized controlled trial. CMAJ. 2022;194:E242-51. 35045989.


Subject(s)
COVID-19 Drug Treatment , Adenosine Monophosphate/analogs & derivatives , Adult , Alanine/analogs & derivatives , Antiviral Agents/therapeutic use , Hospital Mortality , Humans , SARS-CoV-2
5.
PLoS Pathog ; 16(9): e1008744, 2020 09.
Article in English | MEDLINE | ID: mdl-32898182

ABSTRACT

In HIV-hepatitis B virus (HBV) co-infection, adverse liver outcomes including liver fibrosis occur at higher frequency than in HBV-mono-infection, even following antiretroviral therapy (ART) that suppresses both HIV and HBV replication. To determine whether liver disease was associated with intrahepatic or circulating markers of inflammation or burden of HIV or HBV, liver biopsies and blood were collected from HIV-HBV co-infected individuals (n = 39) living in Bangkok, Thailand and naïve to ART. Transient elastography (TE) was performed. Intrahepatic and circulating markers of inflammation and microbial translocation were quantified by ELISA and bead arrays and HIV and HBV infection quantified by PCR. Liver fibrosis (measured by both transient elastography and liver biopsy) was statistically significantly associated with intrahepatic mRNA for CXCL10 and CXCR3 using linear and logistic regression analyses adjusted for CD4 T-cell count. There was no evidence of a relationship between liver fibrosis and circulating HBV DNA, qHBsAg, plasma HIV RNA or circulating cell-associated HIV RNA or DNA. Using immunohistochemistry of liver biopsies from this cohort, intrahepatic CXCL10 was detected in hepatocytes associated with inflammatory liver infiltrates in the portal tracts. In an in vitro model, we infected an HBV-infected hepatocyte cell line with HIV, followed by interferon-γ stimulation. HBV-infected cells lines produced significantly more CXCL10 than uninfected cells lines and this significantly increased in the presence of an increasing multiplicity of HIV infection. Conclusion: Enhanced production of CXCL10 following co-infection of hepatocytes with both HIV and HBV may contribute to accelerated liver disease in the setting of HIV-HBV co-infection.


Subject(s)
Chemokine CXCL10/metabolism , Coinfection/complications , HIV Infections/complications , HIV/isolation & purification , Hepatitis B virus/isolation & purification , Hepatitis B/complications , Liver Cirrhosis/epidemiology , Adult , Australia/epidemiology , Cohort Studies , Coinfection/virology , Female , HIV Infections/virology , Hepatitis B/virology , Humans , Incidence , Liver Cirrhosis/metabolism , Liver Cirrhosis/virology , Male , Netherlands/epidemiology , Prognosis , Thailand/epidemiology
6.
Intern Med J ; 52(1): 37-41, 2022 Jan.
Article in English | MEDLINE | ID: mdl-34524710

ABSTRACT

BACKGROUND: Venous thromboembolic (VTE) complications appear common in hospitalised COVID-19 patients, particularly among critically ill patients in intensive care units. However, there is significant heterogeneity in the reported use of thromboprophylaxis. AIMS: The primary objective was to determine rates of symptomatic VTE in hospitalised COVID-19 patients. Secondary objectives were to assess adherence to an institutional risk-adapted thromboprophylaxis guideline, and rates of bleeding complications. METHODS: A retrospective, single-centre, cohort study was performed in consecutive hospitalised COVID-19 patients over a 6-month period (March to August 2020). Enoxaparin was used as thromboprophylaxis in all patients without a contraindication, with dose adjusted according to disease severity, weight and renal function. RESULTS: Among 86 hospitalised COVID-19 patients, no VTE were identified. Eighty-one (94%) patients received anticoagulation, with 90% adherence to institutional thromboprophylaxis guidelines. Four bleeding events occurred, with one clinically relevant non-major bleeding event and three minor bleeding events. CONCLUSION: Low rates of VTE were identified in hospitalised COVID-19 patients using a risk-adapted thromboprophylaxis protocol.


Subject(s)
COVID-19 , Venous Thromboembolism , Anticoagulants/adverse effects , Australia/epidemiology , Cohort Studies , Humans , Retrospective Studies , SARS-CoV-2 , Venous Thromboembolism/epidemiology , Venous Thromboembolism/prevention & control
7.
Intern Med J ; 52(7): 1129-1134, 2022 07.
Article in English | MEDLINE | ID: mdl-35066963

ABSTRACT

BACKGROUND: The COVID-19 pandemic has affected different parts of Australia in distinct ways across 2020 and 2021. In 2020, Melbourne was the epicentre of COVID-19. As one of the key tertiary centres caring for the patients affected by the outbreaks, the Royal Melbourne Hospital (RMH) managed the majority of the Victorian inpatient caseload. AIMS: To review the demographics, management and outcomes of patients with COVID-19 cared for by the RMH services in 2020. METHODS: A single health service retrospective cohort analysis of demographics, interventions and outcomes was conducted to characterise the RMH experience in 2020. RESULTS: From January to December 2020, 433 patients required admission more than 24 h. The demographics of affected patients and outcomes changed over the course of the study. Overall, 47% (203/433) required oxygen, most frequently (36%; 154/433) with low-flow devices (nasal prongs or hudson mask), and 11% (47/433) of patients required admission to intensive care. We recorded a 30-day mortality of 24% (104/433) mortality overall, rising to over 50% in patients aged over 80 years. CONCLUSIONS: The experience of this health service in 2020 demonstrated changing demographics over time, with associated differences in outcomes; notably marked mortality in older populations, frequent complications and limited inter-site transfer possible with mobilised resources.


Subject(s)
COVID-19 , Aged , Aged, 80 and over , Critical Care , Hospitals , Humans , Pandemics , Retrospective Studies
8.
Health Expect ; 23(6): 1431-1440, 2020 12.
Article in English | MEDLINE | ID: mdl-32918523

ABSTRACT

BACKGROUND: Tuberculosis (TB) elimination strategies in Australia require a focus on groups who are at highest risk of TB infection, such as immigrants from high-burden settings. Understanding attitudes to different strategies for latent TB infection (LTBI) screening and treatment is an important element of justifiable elimination strategies. METHOD: Two community panels were conducted in Melbourne with members of the Vietnamese (n = 11), Sudanese and South Sudanese communities (n = 9). Panellists were provided with expert information about LTBI and different screening and health communication strategies, then deliberated on how best to pursue TB elimination in Australia. FINDINGS: Both panels unanimously preferred LTBI screening to occur pre-migration rather than in Australia. Participants were concerned that post-migration screening would reach fewer migrants, noted that conducting LTBI screening in Australia could stigmatize participants and that poor awareness of LTBI would hamper participation. If targeted screening was to occur in Australia, the Vietnamese panel preferred 'place-based' communication strategies, whereas the Sudanese and South Sudanese panel emphasized that community leaders should lead communication strategies to minimize stigma. Both groups emphasized the importance of maintaining community trust in Australian health service providers, and the need to ensure targeting did not undermine this trust. CONCLUSION: Pre-migration screening was preferred. If post-migration screening is necessary, the potential for stigma should be reduced, benefit and risk profile clearly explained and culturally appropriate communication strategies employed. Cultural attitudes to health providers, personal health management and broader social vulnerabilities of targeted groups need to be considered in the design of screening programs.


Subject(s)
Emigrants and Immigrants , Latent Tuberculosis , Transients and Migrants , Asian People , Australia , Female , Humans , Incidence , Male , Mass Screening
9.
BMC Pulm Med ; 19(1): 152, 2019 Aug 14.
Article in English | MEDLINE | ID: mdl-31412895

ABSTRACT

BACKGROUND: The phase III REMoxTB study prospectively enrolled HIV-positive (with CD4+ count > 250 cells, not on anti-retroviral therapy) and HIV-negative patients. We investigated the incidence of adverse events and cure rates according to HIV status for patients receiving standard TB therapy in the trial. METHODS: Forty-two HIV-positive cases were matched to 220 HIV-negative controls by age, gender, ethnicity, and trial site using coarsened exact matching. Grade 3 and 4 adverse events (AEs) were summarised by MedDRA System Organ Class. Kaplan-Meier curves for time to first grade 3 or 4 AE were constructed according to HIV status with hazard ratios calculated. Patients were considered cured if they were culture negative 18 months after commencing therapy with ≥2 consecutive negative culture results. RESULTS: Twenty of 42 (47.6%) HIV-positive and 34 of 220 (15.5%) HIV-negative patients experienced ≥1 grade 3 or 4 AE, respectively. The majority of these were hepatobiliary disorders that accounted for 12 of 40 (30.0%) events occurring in 6 of 42 (14.3%) HIV-positive patients and for 15 of 60 (25.0%) events occurring in 9 of 220 (4.1%) HIV-negative patients. The median time to first grade 3 or 4 AE was 54 days (IQR 15.5-59.0) for HIV-positive and 29.5 days (IQR 9.0-119.0) for HIV-negative patients, respectively. The hazard ratio for experiencing a grade 3 or 4 AE among HIV-positive patients was 3.25 (95% CI 1.87-5.66, p < 0.01). Cure rates were similar, with 38 of 42 (90.5%) HIV-positive and 195 of 220 (88.6%) HIV-negative patients (p = 0.73) cured at 18 months. CONCLUSIONS: HIV-positive patients receiving standard TB therapy in the REMoxTB study were at greater risk of adverse events during treatment but cure rates were similar when compared to a matched sample of HIV-negative patients.


Subject(s)
Antitubercular Agents/adverse effects , HIV Seropositivity , Tuberculosis, Pulmonary/drug therapy , Adult , Antitubercular Agents/therapeutic use , Ethambutol/adverse effects , Ethambutol/therapeutic use , Female , Humans , Incidence , Isoniazid/adverse effects , Isoniazid/therapeutic use , Linear Models , Male , Multivariate Analysis , Prospective Studies , Pyrazinamide/adverse effects , Pyrazinamide/therapeutic use , Rifampin/adverse effects , Rifampin/therapeutic use , Risk Factors , Treatment Outcome , United Kingdom
10.
BMC Med ; 16(1): 73, 2018 05 21.
Article in English | MEDLINE | ID: mdl-29779492

ABSTRACT

BACKGROUND: Chest radiographs are used for diagnosis and severity assessment in tuberculosis (TB). The extent of disease as determined by smear grade and cavitation as a binary measure can predict 2-month smear results, but little has been done to determine whether radiological severity reflects the bacterial burden at diagnosis. METHODS: Pre-treatment chest x-rays from 1837 participants with smear-positive pulmonary TB enrolled into the REMoxTB trial (Gillespie et al., N Engl J Med 371:1577-87, 2014) were retrospectively reviewed. Two clinicians blinded to clinical details using the Ralph scoring system performed separate readings. An independent reader reviewed discrepant results for quality assessment and cavity presence. Cavitation presence was plotted against time to positivity (TTP) of sputum liquid cultures (MGIT 960). The Wilcoxon rank sum test was performed to calculate the difference in average TTP for these groups. The average lung field affected was compared to log 10 TTP by linear regression. Baseline markers of disease severity and patient characteristics were added in univariable regression analysis against radiological severity and a multivariable regression model was created to explore their relationship. RESULTS: For 1354 participants, the median TTP was 117 h (4.88 days), being 26 h longer (95% CI 16-30, p < 0.001) in patients without cavitation compared to those with cavitation. The median percentage of lung-field affected was 18.1% (IQR 11.3-28.8%). For every 10-fold increase in TTP, the area of lung field affected decreased by 11.4%. Multivariable models showed that serum albumin decreased significantly as the percentage of lung field area increased in both those with and without cavitation. In addition, BMI and logged TTP had a small but significant effect in those with cavitation and the number of severe TB symptoms in the non-cavitation group also had a small effect, whilst other factors found to be significant on univariable analysis lost this effect in the model. CONCLUSIONS: The radiological severity of disease on chest x-ray prior to treatment in smear positive pulmonary TB patients is weakly associated with the bacterial burden. When compared against other variables at diagnosis, this effect is lost in those without cavitation. Radiological severity does reflect the overall disease severity in smear positive pulmonary TB, but we suggest that clinicians should be cautious in over-interpreting the significance of radiological disease extent at diagnosis.


Subject(s)
Thoracic Wall/diagnostic imaging , Tuberculosis, Pulmonary/diagnostic imaging , X-Rays/adverse effects , Adult , Female , Humans , Male , Tuberculosis, Pulmonary/diagnosis , Young Adult
11.
BMC Med ; 16(1): 46, 2018 03 28.
Article in English | MEDLINE | ID: mdl-29592805

ABSTRACT

BACKGROUND: Drug-induced liver injury (DILI) is a common complication of tuberculosis treatment. We utilised data from the REMoxTB clinical trial to describe the incidence of predisposing factors and the natural history in patients with liver enzyme levels elevated in response to tuberculosis treatment. METHODS: Patients received either standard tuberculosis treatment (2EHRZ/4HR), or a 4-month regimen in which moxifloxacin replaced either ethambutol (isoniazid arm, 2MHRZ/2MHR) or isoniazid (ethambutol arm, 2EMRZ/2MR). Hepatic enzymes were measured at 0, 2, 4, 8, 12 and 17 weeks and as clinically indicated during reported adverse events. Patients included were those receiving at least one dose of drug and with two or more hepatic enzyme measurements. RESULTS: A total of 1928 patients were included (639 2EHRZ/4HR, 654 2MHRZ/2MHR and 635 2EMRZ/2MR). DILI was defined as peak alanine aminotransferase (ALT) ≥ 5 times the upper limit of normal (5 × ULN) or ALT ≥ 3 × ULN with total bilirubin > 2 × ULN. DILI was identified in 58 of the 1928 (3.0%) patients at a median time of 28 days (interquartile range IQR 14-56). Of 639 (6.4%) patients taking standard tuberculosis therapy, 41 experienced clinically significant enzyme elevations (peak ALT ≥ 3 × ULN). On standard therapy, 21.1% of patients aged >55 years developed a peak ALT/aspartate aminotransferase (AST) ≥ 3 × ULN (p = 0.01) and 15% of HIV-positive patients experienced a peak ALT/AST ≥ 3 × ULN compared to 9% of HIV-negative patients (p = 0.160). The median peak ALT/AST was higher in isoniazid-containing regimens vs no-isoniazid regimens (p < 0.05), and lower in moxifloxacin-containing arms vs no-moxifloxacin arms (p < 0.05). Patients receiving isoniazid reached a peak ALT ≥ 3 × ULN 9.5 days earlier than those on the ethambutol arm (median time of 28 days vs 18.5 days). Of the 67 Asian patients with a peak ALT/AST ≥ 3 × ULN, 57 (85.1%) were on an isoniazid-containing regimen (p = 0.008). CONCLUSIONS: Our results provide evidence of the risk of DILI in tuberculosis patients on standard treatment. Older patients on standard therapy, HIV-positive patients, Asian patients and those receiving isoniazid were at higher risk of elevated enzyme levels. Monitoring hepatic enzymes during the first 2 months of standard therapy detected approximately 75% of patients with a peak enzyme elevation ≥3 × ULN, suggesting this should be a standard of care. These results provide evidence for the potential of moxifloxacin in hepatic sparing.


Subject(s)
Chemical and Drug Induced Liver Injury/etiology , Tuberculosis/complications , Adolescent , Adult , Female , Humans , Incidence , Male , Middle Aged , Tuberculosis/drug therapy , Young Adult
12.
BMC Infect Dis ; 18(1): 317, 2018 07 11.
Article in English | MEDLINE | ID: mdl-29996783

ABSTRACT

BACKGROUND: The incidence and severity of tuberculosis chemotherapy toxicity is poorly characterised. We used data available from patients in the REMoxTB trial to provide an assessment of the risks associated with the standard regimen and two experimental regimens containing moxifloxacin. METHODS: All grade 3 & 4 adverse events (AEs) and their relationship to treatment for patients who had taken at least one dose of therapy in the REMoxTB clinical trial were recorded. Univariable logistic regression was used to test the relationship of baseline characteristics to the incidence of grade 3 & 4 AEs and significant characteristics (p < 0.10) were incorporated into a multivariable model. The timing of AEs during therapy was analysed in standard therapy and the experimental arms. Logistic regression was used to investigate the relationship between AEs (total and related-only) and microbiological cure on treatment. RESULTS: In the standard therapy arm 57 (8.9%) of 639 patients experienced ≥1 related AEs with 80 of the total 113 related events (70.8%) occurring in the intensive phase of treatment. Both four-month experimental arms ("isoniazid arm" with moxifloxacin substituted for ethambutol & "ethambutol arm" with moxifloxacin substituted for isoniazid) had a lower total of related grade 3 & 4 AEs than standard therapy (63 & 65 vs 113 AEs). Female gender (adjOR 1.97, 95% CI 0.91-1.83) and HIV-positive status (adjOR 3.33, 95% CI 1.55-7.14) were significantly associated with experiencing ≥1 related AE (p < 0.05) on standard therapy. The most common adverse events on standard therapy related to hepatobiliary, musculoskeletal and metabolic disorders. Patients who experienced ≥1 related AE were more likely to fail treatment or relapse (adjOR 3.11, 95% CI 1.59-6.10, p < 0.001). CONCLUSIONS: Most AEs considered related to standard therapy occurred in the intensive phase of treatment with female patients and HIV-positive patients demonstrating a significantly higher risk of AEs during treatment. Almost a tenth of standard therapy patients had a significant side effect, whereas both experimental arms recorded a lower incidence of toxicity. That patients with one or more AE are more likely to fail treatment suggests that treatment outcomes could be improved by identifying such patients through targeted monitoring.


Subject(s)
Antitubercular Agents/adverse effects , Ethambutol/adverse effects , Isoniazid/adverse effects , Moxifloxacin/adverse effects , Tuberculosis, Pulmonary/drug therapy , Adult , Clinical Protocols , Female , HIV Seropositivity , Humans , Incidence , Male , Treatment Outcome
13.
BMC Med ; 15(1): 192, 2017 10 27.
Article in English | MEDLINE | ID: mdl-29073910

ABSTRACT

BACKGROUND: The use of early morning sputum samples (EMS) to diagnose tuberculosis (TB) can result in treatment delay given the need for the patient to return to the clinic with the EMS, increasing the chance of patients being lost during their diagnostic workup. However, there is little evidence to support the superiority of EMS over spot sputum samples. In this new analysis of the REMoxTB study, we compare the diagnostic accuracy of EMS with spot samples for identifying Mycobacterium tuberculosis pre- and post-treatment. METHODS: Patients who were smear positive at screening were enrolled into the study. Paired sputum samples (one EMS and one spot) were collected at each trial visit pre- and post-treatment. Microscopy and culture on solid LJ and liquid MGIT media were performed on all samples; those missing corresponding paired results were excluded from the analyses. RESULTS: Data from 1115 pre- and 2995 post-treatment paired samples from 1931 patients enrolled in the REMoxTB study were analysed. Patients were recruited from South Africa (47%), East Africa (21%), India (20%), Asia (11%), and North America (1%); 70% were male, median age 31 years (IQR 24-41), 139 (7%) co-infected with HIV with a median CD4 cell count of 399 cells/µL (IQR 318-535). Pre-treatment spot samples had a higher yield of positive Ziehl-Neelsen smears (98% vs. 97%, P = 0.02) and LJ cultures (87% vs. 82%, P = 0.006) than EMS, but there was no difference for positivity by MGIT (93% vs. 95%, P = 0.18). Contaminated and false-positive MGIT were found more often with EMS rather than spot samples. Surprisingly, pre-treatment EMS had a higher smear grading and shorter time-to-positivity, by 1 day, than spot samples in MGIT culture (4.5 vs. 5.5 days, P < 0.001). There were no differences in time to positivity in pre-treatment LJ culture, or in post-treatment MGIT or LJ cultures. Comparing EMS and spot samples in those with unfavourable outcomes, there were no differences in smear or culture results, and positive results were not detected earlier in Kaplan-Meier analyses in either EMS or spot samples. CONCLUSIONS: Our data do not support the hypothesis that EMS samples are superior to spot sputum samples in a clinical trial of patients with smear positive pulmonary TB. Observed small differences in mycobacterial burden are of uncertain significance and EMS samples do not detect post-treatment positives any sooner than spot samples.


Subject(s)
Mycobacterium tuberculosis , Sputum/microbiology , Tuberculosis, Pulmonary/diagnosis , Adult , Africa, Eastern , Asia , CD4 Lymphocyte Count , Female , HIV Infections/complications , Humans , India , Male , Microscopy/methods , Middle Aged , North America , Sensitivity and Specificity , South Africa , Specimen Handling , Time Factors , Tuberculosis, Pulmonary/complications , Young Adult
16.
EBioMedicine ; 102: 105054, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38518655

ABSTRACT

BACKGROUND: In people living with HIV-HBV, liver fibrosis progression can occur even with suppressive antiretroviral therapy (ART). We investigated the relationship between liver fibrosis and biomarkers of inflammation, apoptosis, and microbial translocation. METHODS: In this observational cohort study adults living with HIV-HBV already on effective ART were recruited in Australia and Thailand and followed for 3 years including 6 monthly clinical review and blood tests and annual transient elastography. Differences in clinical and laboratory predictors of liver fibrosis progression were tested followed by regression analysis adjusted for CD4+ T-cells at study entry. A linear mixed model was fitted to longitudinal data to explore changes over time. FINDINGS: 67 participants (85% male, median age 49 y) were followed for 175 person-years. Median duration of ART was 10 years (interquartile range (IQR) 8-16 years). We found 11/59 (19%) participants during 3-years follow-up (6/100 person-years) met the primary endpoint of liver disease progression, defined as increased Metavir stage from baseline to final scan. In regression analysis, progressors compared to non-progressors had higher levels of high mobility group box 1 protein (HGMB1), (median (IQR) 3.7 (2.6-5.0) and 2.4 ng/mL (1.5-3.4) respectively, adjusted relative risk 1.47, 95% CI [1.00, 2.17]) and lower nadir CD4+ T-cell percentage (median 4% (IQR 2-8) and 11% (4-15) respectively (relative risk 0.93, 95% CI [0.88, 0.98]). INTERPRETATION: Progression in liver fibrosis occurs in people with HIV-HBV on suppressive ART. Fibrosis progression was associated with higher HMGB1 and lower percentage nadir CD4+ T-cell count, highlighting the importance of early initiation of HBV-active ART. FUNDING: This work was supported by NHMRC project grant 1101836; NHMRC practitioner fellowship 1138581 and NHMRC program grant 1149990. The funder had no role in study design, data collection, data analysis, interpretation, writing of this manuscript or decision to submit for publication.


Subject(s)
Coinfection , HIV Infections , Adult , Humans , Male , Middle Aged , Female , Hepatitis B virus , HIV Infections/complications , HIV Infections/drug therapy , Liver Cirrhosis/complications , Liver Cirrhosis/diagnosis , Disease Progression , CD4 Lymphocyte Count
17.
Cureus ; 15(11): e48219, 2023 Nov.
Article in English | MEDLINE | ID: mdl-38050506

ABSTRACT

The COVID-19 pandemic caused significant stress and anxiety among the general population and healthcare workers (HCWs) worldwide. India is one of the countries severely impacted by the pandemic. This review explores the gender perspective of mental health conditions among HCWs and job loss during the pandemic in India. Electronic databases (PubMed, Scopus, and Web of Science) were searched for articles published till March 2021. Studies that reported the prevalence of depression, anxiety, stress, and worry among HCWs in India during the pandemic and job loss in both males and females due to COVID-19 were included. We used a random-effects model to estimate pooled prevalence rates with 95% CIs. We assessed heterogeneity using the I2 statistic. The meta-analysis included 11 studies; the pooled prevalence of depression, anxiety, stress, and worry among HCWs was 34.9% (95%CI 27.33, 42.47), 35.4% (95%CI 24.46, 46.33), 32.9% (95%CI 25.43, 40.37), and 42.87% (95%CI 25.83, 59.91), respectively. The pooled prevalence of job loss due to COVID-19 was 16.6% (95%CI 8.34, 19.66). We employed meta-regression and Egger's regression for publication bias. The meta-analysis findings suggest that the prevalence of depression, anxiety, stress, and worry among HCWs in India during COVID-19 was high. Furthermore, job loss due to COVID-19 has also been prevalent in India. These findings emphasize the need for mental health support for HCWs and those who have lost their jobs during the pandemic. It is essential to prioritize mental health and job creation policies in India to support individuals affected by COVID-19.

18.
PLoS One ; 18(3): e0282884, 2023.
Article in English | MEDLINE | ID: mdl-36943855

ABSTRACT

BACKGROUND: Regionality is often a significant factor in tuberculosis (TB) management and outcomes worldwide. A wide range of context-specific factors may influence these differences and change over time. We compared TB treatment in regional and metropolitan areas, considering demographic and temporal trends affecting TB diagnosis and outcomes. METHODS: Retrospective analyses of data for patients notified with TB in Victoria, Australia, were conducted. The study outcomes were treatment delays and treatment outcomes. Multivariable Cox proportional hazard model analyses were performed to investigate the effect of regionality in the management of TB. Six hundred and eleven (7%) TB patients were notified in regional and 8,163 (93%) in metropolitan areas between 1995 and 2019. Of the 611 cases in the regional cohort, 401 (66%) were overseas-born. Fifty-one percent of the overseas-born patients in regional Victoria developed TB disease within five years of arrival in Australia. Four cases of multidrug-resistant tuberculosis were reported in regional areas, compared to 97 cases in metropolitan areas. A total of 3,238 patients notified from 2012 to 2019 were included in the survival analysis. The time follow-up for patient delay started at symptom onset date, and the event was the presentation to the healthcare centre. For healthcare system delay, follow-up time began at the presentation to the healthcare centre, and the event was commenced on TB treatment. Cases with extrapulmonary TB in regional areas have a non-significantly longer healthcare system delay than patients in metropolitan (median 64 days versus 54 days, AHR = 0.8, 95% CI 0.6-1.0, P = 0.094). CONCLUSION: Tuberculosis in regional Victoria is common among the overseas-born population, and patients with extrapulmonary TB in regional areas experienced a non-significant minor delay in treatment commencement with no apparent detriment to treatment outcomes. Improving access to LTBI management in regional areas may reduce the burden of TB.


Subject(s)
Tuberculosis, Extrapulmonary , Tuberculosis , Humans , Victoria/epidemiology , Retrospective Studies , Incidence , Public Health , Tuberculosis/drug therapy , Tuberculosis/epidemiology , Tuberculosis/diagnosis
19.
AIDS ; 37(3): 401-411, 2023 03 01.
Article in English | MEDLINE | ID: mdl-36384811

ABSTRACT

OBJECTIVE: Liver disease is accelerated in people with HIV (PWH) with hepatitis B virus (HBV) coinfection. We hypothesized that liver fibrosis in HIV-HBV is triggered by increased hepatocyte apoptosis, microbial translocation and/or HIV/HBV viral products. DESIGN: Sera from PWH with HBV coinfection versus from those with HBV only or putative mediators were used to examine the pathogenesis of liver disease in HIV-HBV. METHODS: We applied sera from PWH and HBV coinfection versus HBV alone, or putative mediators (including HMGB1), to primary human hepatic stellate cells (hHSC) and examined pro-fibrogenic changes at the single cell level using flow cytometry. High mobility group box 1 (HMGB1) levels in the applied sera were assessed according to donor fibrosis stage. RESULTS: Quantitative flow cytometric assessment of pro-fibrogenic and inflammatory changes at the single cell level revealed an enhanced capacity for sera from PWH with HBV coinfection to activate hHSC. This effect was recapitulated by lipopolysaccharide, HIV-gp120, hepatocyte conditioned-media and the alarmin HMGB1. Induction of hepatocyte cell death increased their pro-fibrogenic potential, an effect blocked by HMGB1 antagonist glycyrrhizic acid. Consistent with a role for this alarmin, HMGB1 levels were elevated in sera from PWH and hepatitis B coinfection compared to HBV alone and higher in those with HIV-HBV with liver fibrosis compared to those without. CONCLUSIONS: Sera from PWH and HBV coinfection have an enhanced capacity to activate primary hHSC. We identified an increase in circulating HMGB1 which, in addition to HIV-gp120 and translocated microbial products, drove pro-fibrogenic changes in hHSC, as mechanisms contributing to accelerated liver disease in HIV-HBV.


Subject(s)
Coinfection , HIV Infections , HMGB1 Protein , Hepatitis B , Humans , Hepatitis B virus , Alarmins , Hepatitis B/complications , Liver Cirrhosis/pathology
20.
EBioMedicine ; 87: 104391, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36502576

ABSTRACT

BACKGROUND: HIV can infect multiple cells in the liver including hepatocytes, Kupffer cells and infiltrating T cells, but whether HIV can persist in the liver in people with HIV (PWH) on suppressive antiretroviral therapy (ART) remains unknown. METHODS: In a prospective longitudinal cohort of PWH and hepatitis B virus (HBV) co-infection living in Bangkok, Thailand, we collected blood and liver biopsies from 18 participants prior to and following ART and quantified HIV and HBV persistence using quantitative (q)PCR and RNA/DNAscope. Antiretroviral (ARV) drug levels were quantified using mass spectroscopy. FINDINGS: In liver biopsies taken prior to ART, HIV DNA and HIV RNA were detected by qPCR in 53% (9/17) and 47% (8/17) of participants respectively. Following a median ART duration of 3.4 years, HIV DNA was detected in liver in 61% (11/18) of participants by either qPCR, DNAscope or both, but only at very low and non-quantifiable levels. Using immunohistochemistry, HIV DNA was observed in both hepatocytes and liver infiltrating CD4+ T cells on ART. HIV RNA was not detected in liver biopsies collected on ART, by either qPCR or RNAscope. All ARVs were clearly detected in liver tissue. INTERPRETATION: Persistence of HIV DNA in liver in PWH on ART represents an additional reservoir that warrants further investigation. FUNDING: National Health and Medical Research Council of Australia (Project Grant APP1101836, 1149990, and 1135851); This project has been funded in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. 75N91019D00024.


Subject(s)
Coinfection , HIV Infections , Hepatitis B , Humans , Prospective Studies , Thailand , Hepatitis B/complications , HIV Infections/complications , HIV Infections/drug therapy , Hepatitis B virus/genetics , Anti-Retroviral Agents/pharmacology , Anti-Retroviral Agents/therapeutic use , DNA, Viral/genetics , Hepatocytes
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