National trends in retreatment of HCV due to reinfection or treatment failure in Australia

Background & Aims: Population-level uptake of direct-acting antiviral (DAA) treatment for hepatitis C virus (HCV) infection, including retreatment, can be estimated through administrative pharmaceutical dispensation data. However, the reasons for retreatment are not captured in these data. We developed a machine learning model to classify retreatments as reinfection or treatment failure at a national level. Methods: Retreatment data from the REACH-C cohort (n = 10,843 treated with DAAs; n = 320 retreatments with known reason), were used to train a random forest model. Nested cross validation was undertaken to assess model performance and to optimise hyperparameters. The model was applied to data on DAA retreatment dispensed during 2016-2021 in Australia, to identify the reason for retreatment (treatment failure or reinfection). Results: Average predictive accuracy, precision, sensitivity, specificity and F1-score for the model were 96.3%, 96.5%, 96.3%, 96.3% and 96.3%, respectively. Nationally, 95,272 individuals initiated DAAs, with treatment uptake declining from 32,454 in 2016 to 6,566 in 2021. Of those treated, 6,980 (7%) were retreated. Our model classified 51.8% (95% CI 46.7–53.6%; n = 3,614) of cases as reinfection and 48.2% (95% CI 46.4–53.3%; n = 3,366) as treatment failure. Retreatment for reinfection increased steadily over the study period from 14 in 2016 to 1,092 in 2020, stabilising in 2021. Retreatment for treatment failure increased from 73 in 2016 to 1,077 in 2019, then declined to 515 in 2021. Among individuals retreated for treatment failure, 50% had discontinued initial treatment. Conclusions: We used a novel methodology with high classification accuracy to evaluate DAA retreatment patterns at a national level. Increases in retreatment uptake for treatment failure corresponded to the availability of pangenotypic and salvage regimens. Increasing retreatment uptake for reinfection likely reflects increasing reinfection incidence. Impact and implications: This study used machine learning methodologies to analyse national administrative data and characterise trends in HCV retreatment due to reinfection and treatment failure. Retreatment for reinfection increased over time, reflecting increasing numbers of people at risk for reinfection following HCV cure. Increased retreatment for treatment failure corresponded to the availability of pangenotypic and salvage DAA regimens. The findings of this study can be used by public health agencies and policy makers to guide and assess HCV elimination strategies, while the novel methodology for monitoring trends in HCV retreatment has the potential to be used in other settings, and health conditions

Maximum levels of hepatitis C virus lipoviral particles are associated with early and persistent infection

Background & Aims: Hepatitis C virus (HCV) is bound to plasma lipoproteins and circulates as an infectious lipoviral particle (LVP). Experimental evidence indicates that LVPs have decreased susceptibility to antibody-mediated neutralisation and higher infectivity. This study tested the hypothesis that LVPs are required to establish persistent infection, and conversely, low levels of LVP in recent HCV infection increase the probability of spontaneous HCV clearance. Methods: LVP in non-fasting plasma was measured using the concentration of HCV RNA bound to large >100 nm sized lipoproteins after ex vivo addition of a lipid emulsion, that represented the maximum concentration of LVP (maxi-LVP). This method correlated with LVP in fasting plasma measured using iodixanol density gradient ultracentrifugation. Maxi-LVP was measured in a cohort of 180 HCV participants with recent HCV infection and detectable HCV RNA from the Australian Trial in Acute Hepatitis C (ATAHC) and Hepatitis C Incidence and Transmission Study in prison (HITS-p) cohorts. Results: Spontaneous clearance occurred in 15% (27 of 180) of individuals. In adjusted analyses, low plasma maxi-LVP level was independently associated with spontaneous HCV clearance (≤827 IU/ml; adjusted odds ratio 3.98, 95% CI: 1.02, 15.51, P = 0.047), after adjusting for interferon lambda-3 rs8099917 genotype, estimated duration of HCV infection and total HCV RNA level. Conclusions: Maxi-LVP is a biomarker for the maximum concentration of LVP in non-fasting samples. Low maxi-LVP level is an independent predictor of spontaneous clearance of acute HCV

Effectiveness of direct-acting antiviral therapy among Aboriginal and Torres Strait Islander peoples with HCV infection in Australia: A national real-world cohort (REACH-C)

Aboriginal and Torres Strait Islander peoples experience a disproportionate burden of hepatitis C virus (HCV) infection. This study assessed the effectiveness of direct-acting antiviral (DAA) therapy among Aboriginal peoples in the three years following universal access in Australia. REACH-C, a national multicentre prospective cohort study, evaluated HCV treatment outcomes from sequential DAA initiations across 33 health services between March 2016 and June 2019. DAA effectiveness was assessed by sustained virological response (SVR) in the total (full analysis set) and effectiveness (modified analysis set excluding those lost to follow-up) populations. Overall, 915 (10%) Aboriginal and 8095 (90%) non-Indigenous people commenced DAA therapy, of whom 30% and 16% reported current injecting drug use and 73% and 42% were treated in primary care, respectively. SVR in the total and effectiveness populations was 74% and 94% among Aboriginal people and 82% and 94% among non-Indigenous people, with loss to follow-up contributing to lower SVR in the total population analysis (22% Aboriginal, 13% non-Indigenous). Among Aboriginal people, returning for follow-up was positively associated with older age (aOR 1.20; 95% CI 1.04, 1.39) and SVR was negatively associated with cirrhosis (aOR 0.39; 95% CI 0.19, 0.80) and prior DAA treatment (aOR 0.14; 95% CI 0.04, 0.49). Factors reflecting higher vulnerability or inequity were not associated with returning for testing or SVR. DAA therapy was highly effective among Aboriginal peoples with HCV treated through primary and tertiary services. Tailored community-led interventions are necessary to optimize follow-up and engagement. Sustained DAA uptake and equitable access to care, treatment and prevention are required for HCV elimination

稲垣足穂『少年愛の美学』の読書論的研究 --念者としての語り--

千葉大学大学院人文社会科学研究科研究プロジェクト報告書第144集 『パフォーマンスの民族誌的研究』橋本裕之

Neprilysin inhibition for pulmonary arterial hypertension: a randomized, double-blind, placebo-controlled, proof-of-concept trial

This is the peer reviewed version of the following article: Hobbs AJ, Moyes AJ, Baliga RS, et al. Neprilysin inhibition for pulmonary arterial hypertension: a randomized, double‐blind, placebo‐controlled, proof‐of‐concept trial. Br J Pharmacol. 2019. https://doi.org/10.1111/bph.14621, which has been published in final form at https://doi.org/10.1111/bph.14621. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived VersionsThis work was supported by a British Heart Foundation Project Grant (PG/11/88/28992) and the National Institutes for Health Research, Comprehensive Biomedical Research Centre award to UC

An HIV epidemic is ready to emerge in the Philippines

<p>Abstract</p> <p>Background</p> <p>The state of the HIV epidemic in the Philippines has been described as "low and slow", which is in stark contrast to many other countries in the region. A review of the conditions for HIV spread in the Philippines is necessary.</p> <p>Methods</p> <p>We evaluated the current epidemiology, trends in behaviour and public health response in the Philippines to identify factors that could account for the current HIV epidemic, as well as to review conditions that may be of concern for facilitating an emerging epidemic.</p> <p>Results</p> <p>The past control of HIV in the Philippines cannot be attributed to any single factor, nor is it necessarily a result of the actions of the Filipino government or other stakeholders. Likely reasons for the epidemic's slow development include: the country's geography is complicated; injecting drug use is relatively uncommon; a culture of sexual conservatism exists; sex workers tend to have few clients; anal sex is relatively uncommon; and circumcision rates are relatively high.</p> <p>In contrast, there are numerous factors suggesting that HIV is increasing and ready to emerge at high rates, including: the lowest documented rates of condom use in Asia; increasing casual sexual activity; returning overseas Filipino workers from high-prevalence settings; widespread misconceptions about HIV/AIDS; and high needle-sharing rates among injecting drug users.</p> <p>There was a three-fold increase in the rate of HIV diagnoses in the Philippines between 2003 and 2008, and this has continued over the past year. HIV diagnoses rates have noticeably increased among men, particularly among bisexual and homosexual men (114% and 214% respective increases over 2003-2008). The average age of diagnosis has also significantly decreased, from approximately 36 to 29 years.</p> <p>Conclusions</p> <p>Young adults, men who have sex with men, commercial sex workers, injecting drug users, overseas Filipino workers, and the sexual partners of people in these groups are particularly vulnerable to HIV infection. There is no guarantee that a large HIV epidemic will be avoided in the near future. Indeed, an expanding HIV epidemic is likely to be only a matter of time as the components for such an epidemic are already present in the Philippines.</p

Projections of the healthcare costs and disease burden due to hepatitis C infection under different treatment policies in Malaysia, 2018-2040

The World Health Organisation (WHO) has set ambitious goals to reduce the global disease burden associated with, and eventually eliminate, viral hepatitis

Bridging the data gaps in the epidemiology of hepatitis C virus infection in Malaysia using multi-parameter evidence synthesis

BACKGROUND: Collecting adequate information on key epidemiological indicators is a prerequisite to informing a public health response to reduce the impact of hepatitis C virus (HCV) infection in Malaysia. Our goal was to overcome the acute data shortage typical of low/middle income countries using statistical modelling to estimate the national HCV prevalence and the distribution over transmission pathways as of the end of 2009. METHODS: Multi-parameter evidence synthesis methods were applied to combine all available relevant data sources - both direct and indirect - that inform the epidemiological parameters of interest. RESULTS: An estimated 454,000 (95% credible interval [CrI]: 392,000 to 535,000) HCV antibody-positive individuals were living in Malaysia in 2009; this represents 2.5% (95% CrI: 2.2-3.0%) of the population aged 15-64 years. Among males of Malay ethnicity, for 77% (95% CrI: 69-85%) the route of probable transmission was active or a previous history of injecting drugs. The corresponding proportions were smaller for male Chinese and Indian/other ethnic groups (40% and 71%, respectively). The estimated prevalence in females of all ethnicities was 1% (95% CrI: 0.6 to 1.4%); 92% (95% CrI: 88 to 95%) of infections were attributable to non-drug injecting routes of transmission. CONCLUSIONS: The prevalent number of persons living with HCV infection in Malaysia is estimated to be very high. Low/middle income countries often lack a comprehensive evidence base; however, evidence synthesis methods can assist in filling the data gaps required for the development of effective policy to address the future public health and economic burden due to HCV. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-014-0564-6) contains supplementary material, which is available to authorized users

Neurocognitive function in HIV infected patients on antiretroviral therapy

OBJECTIVE To describe factors associated with neurocognitive (NC) function in HIV-positive patients on stable combination antiretroviral therapy. DESIGN We undertook a cross-sectional analysis assessing NC data obtained at baseline in patients entering the Protease-Inhibitor-Monotherapy-Versus-Ongoing-Triple therapy (PIVOT) trial. MAIN OUTCOME MEASURE NC testing comprised of 5 domains. Raw results were z-transformed using standard and demographically adjusted normative datasets (ND). Global z-scores (NPZ-5) were derived from averaging the 5 domains and percentage of subjects with test scores >1 standard deviation (SD) below population means in at least two domains (abnormal Frascati score) calculated. Patient characteristics associated with NC results were assessed using multivariable linear regression. RESULTS Of the 587 patients in PIVOT, 557 had full NC results and were included. 77% were male, 68% Caucasian and 28% of Black ethnicity. Mean (SD) baseline and nadir CD4+ lymphocyte counts were 553(217) and 177(117) cells/µL, respectively, and HIV RNA was <50 copies/mL in all. Median (IQR) NPZ-5 score was -0.5 (-1.2/-0) overall, and -0.3 (-0.7/0.1) and -1.4 (-2/-0.8) in subjects of Caucasian and Black ethnicity, respectively. Abnormal Frascati scores using the standard-ND were observed in 51%, 38%, and 81%, respectively, of subjects overall, Caucasian and Black ethnicity (p<0.001), but in 62% and 69% of Caucasian and Black subjects using demographically adjusted-ND (p = 0.20). In the multivariate analysis, only Black ethnicity was associated with poorer NPZ-5 scores (P<0.001). CONCLUSIONS In this large group of HIV-infected subjects with viral load suppression, ethnicity but not HIV-disease factors is closely associated with NC results. The prevalence of abnormal results is highly dependent on control datasets utilised. TRIAL REGISTRY ClinicalTrials.gov, NCT01230580