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Abstract: Surveillance case definitions are utilised to understand the epidemiology of communicable diseases and to inform public health actions. We report a case of hepatitis B infection that meets the case definition for newly acquired infection. However, further investigation revealed that this was most likely past resolved hepatitis B infection with subsequent reactivation secondary to immunosuppression, rather than a newly acquired infection. This case highlights the importance of thorough case and clinician interviews, in combination with detailed assessment of pathology results in collaboration with treating clinicians, to determine the most appropriate public health actions.
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Hepatite B , Saúde Pública , Humanos , Hepatite B/epidemiologia , Masculino , Vírus da Hepatite B/imunologia , Pessoa de Meia-Idade , Feminino , Vigilância da PopulaçãoRESUMO
Newly formed local public health units in Victoria have been established to support a place-based approach that tailors and delivers public health initiatives and responds to public health incidents and issues. Initially, post-establishment of these units, public health activities focused on the prevention and control of communicable diseases. In 2022, mpox emerged as a global public health threat. As case numbers rose across Australia, local public health units in Victoria were engaged by the Department of Health to support a localized response to this new threat. The South East Public Health Unit, Monash Health, developed a number of targeted initiatives to control the local spread of mpox, ranging from capacity building of health professionals to increase early diagnosis, contact tracing, facilitating vaccine delivery, and community engagement. This contributed to effective local elimination within 6 months, demonstrating how LPHUs are well placed to engage with local communities and health care providers to respond rapidly to newly emerging public health threats.
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Mpox , Humanos , Saúde PúblicaRESUMO
Background: Well tolerated antivirals administered early in the course of COVID-19 infection when the viremia is highest could prevent progression to severe disease. Favipiravir inhibits SARS-CoV-2 viral replication in vitro with evidence of clinical benefit in open label trials. Placebo controlled studies of people with early symptomatic COVID-19 with regular assessments of SARS-CoV-2 viral load can determine if it has an antiviral effect and improves clinical outcomes. Methods: People with PCR-confirmed COVID-19 and 5 days or less of symptoms were randomised 1:1 to favipiravir 1800 mg on day 1, then 800 mg twice daily or matched placebo for 14 days. SARS-CoV-2 viral load was quantitated from second daily self-collected nose-throat swabs while receiving study drug. The primary endpoint was time to virological cure defined as 2 successive swabs negative for SARS-CoV-2 by PCR and secondary outcomes were progression of disease severity, symptom resolution and safety. Findings: Between 31 July 2020 and 19 September 2021, 200 people were enrolled (199 in the community, 1 in hospital) with 190 receiving one or more doses of drug (modified intention to treat [mITT] population). There was no difference in time to virological cure (Log-rank p=0.6 comparing Kaplan Meier curves), progression to hospitalisation (14 favipiravir, 9 placebo; p=0.38), time to symptom resolution (cough, fever, sore throat) and there were no deaths. 51 people related an adverse event that was possibly drug related, but these were evenly distributed (n=24 favipiravir, n=27 placebo). Sensitivity analyses where the definition of virological cure was changed to: a single negative PCR, exclude datapoints based on the presence or absence of human DNA in the swab, a SARS-CoV-2 viral load < 300 copies/mL being considered negative all demonstrated no difference between arms. Interpretation: Favipiravir does not improve the time to virological cure or clinical outcomes and shows no evidence of an antiviral effect when treating early symptomatic COVID-19 infection. Funding: The study was supported in part by grants from the Commonwealth Bank Australia, the Lord Mayor's Charitable Foundation, Melbourne Australia and the Orloff Family Charitable Trust, Melbourne, Australia. JHM is supported by the Medical Research Future Fund, AYP, JT are supported by the Australian National Health and Medical Research Council.
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COVID-19 , Viroses , Humanos , Hospedeiro Imunocomprometido , Sistema Respiratório , SARS-CoV-2RESUMO
Background: Pre-exposure prophylaxis (PrEP) is the use of HIV anti-retroviral therapy to prevent HIV transmission in people at high risk of HIV acquisition. PrEP is highly efficacious when taken either daily, or in an on-demand schedule. In Australia co-formulated tenofovir-emtricitabine is registered for daily use for PrEP, however, this co-formulation is not listed yet on the national subsidized medicines list. We describe a study protocol that aims to demonstrate if the provision of PrEP to up to 3800 individuals at risk of HIV in Victoria, Australia reduces HIV incidence locally by 25% generally and 30% among GBM. Methods: PrEPX is a population level intervention study in Victoria, Australia in which generic PrEP will be delivered to 3800 individuals for up to 36 months. Study eligibility is consistent with the recently updated 2017 Australian PrEP guidelines. Participants will attend study clinics, shared care clinics, or outreach clinics for quarterly HIV/STI screening, biannual renal function tests and other clinical care as required. Study visits and STI diagnoses will be recorded electronically through the ACCESS surveillance system. At each study visit participants will be invited to complete behavioral surveys that collect demographics and sexual risk data. Diagnosis and behavioral data will be compared between PrEPX participants and other individuals testing within the ACCESS surveillance system. A subset of participants will complete in depth surveys and interviews to collect attitudes, beliefs and acceptability data. Participating clinics will provide clinic level data on implementation and management of PrEPX participants. The population level impact on HIV incidence will be assessed using Victorian HIV notification data. Discussion: This study will collect evidence on the real world impact of delivery of PrEP to 3800 individuals at risk of acquiring HIV in Victoria. This study will provide important information for the broader implementation of PrEP planning upon listing of the tenofovir-emtricitabine on the national subsidized list of medicines. The study is registered on the Australian New Zealand Clinical Trials Registry (ACTRN12616001215415).
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OBJECTIVES: Completion rates for HIV postexposure prophylaxis (PEP) are often low. We investigated the adherence and safety of dolutegravir (DTG; 50âmg daily) with tenofovir disoproxil fumarate-emtricitabine (TDF-FTC; 300/200âmg, respectively) as three-drug PEP in gay and bisexual men. DESIGN: Open-label, single-arm study at three sexual health clinics and two emergency departments in Australia. METHODS: In total, 100 HIV-uninfected gay and bisexual men requiring PEP received DTG and TDF-FTC for 28 days. The primary end point was PEP failure (premature PEP cessation or primary HIV infection through week 12). Additional end points were adherence by self-report (nâ=â98) and pill count (nâ=â55), safety, and plasma drug levels at day 28. RESULTS: PEP completion was 90% (95% confidence interval 84-96%). Failures (occurring at a median 9 days, interquartile range 3-16) comprised loss to follow-up (9%) and adverse event resulting in study drug discontinuation (headache, 1%). No participant was found to acquire HIV through week 12. Adherence to PEP was 98% by self-report and in the 55 participants with corresponding pill count data. The most common clinical adverse events were fatigue (26%), nausea (25%), diarrhoea (21%), and headache (10%). There were only four grade 3-4 subjective adverse events. The most common laboratory adverse event was raised alanine aminotransferase (22%), but there was no case of clinical hepatitis. At day 28, the mean estimated glomerular filtration rate decrease was 14âml/min/1.73m (SD 17, Pâ=â0.001); an estimated glomerular filtration rate of less than 60âml/min/1.73m occurred in 3%. CONCLUSIONS: DTG with TDF-FTC is a well tolerated option for once-daily PEP.
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Fármacos Anti-HIV/administração & dosagem , Quimioprevenção/métodos , Emtricitabina/administração & dosagem , Infecções por HIV/prevenção & controle , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , Profilaxia Pós-Exposição/métodos , Tenofovir/administração & dosagem , Fármacos Anti-HIV/efeitos adversos , Austrália , Quimioprevenção/efeitos adversos , Transmissão de Doença Infecciosa/prevenção & controle , Emtricitabina/efeitos adversos , Infecções por HIV/transmissão , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Humanos , Masculino , Adesão à Medicação , Oxazinas , Piperazinas , Piridonas , Minorias Sexuais e de Gênero , Tenofovir/efeitos adversos , Falha de TratamentoRESUMO
Background International non-occupational post-exposure prophylaxis (NPEP) guidelines recommend routine use of three drug NPEP regimens, despite absence of evidence for greater prevention efficacy compared with two drug regimens. This study examines the potential for excess HIV seroconversions among high-risk men who have sex with men (MSM) reporting receptive anal intercourse with a source of unknown HIV serostatus (RAIU) following a two-drug versus a three-drug NPEP regimen. METHODS: Data for MSM in the Victorian NPEP service database between 10 August 2005 and 31 December 2012 were linked with all Victorian HIV notifications up to 31 December 2013. The primary outcome was NPEP failure following NPEP presentation among MSM reporting RAIU, stratified by the number of drugs prescribed. RESULTS: Among 1482 MSM reporting 2002 episodes of RAIU and prescribed two- or three-drug NPEP, 70 seroconverted to HIV, but only 19 were considered possible NPEP failures. HIV diagnosis incidence among men reporting RAIU was 1.2/100 person years (PY) (95%CI=1.0-1.6); 1.1/100 PY (95%CI=0.8-1.4) among MSM prescribed two drugs and 2.2/100 PY (95%CI=1.4-3.7) among MSM prescribed three drugs (P<0.01). Of the 19 possible NPEP failures, 13 (0.7%) were prescribed two drugs and six (2.7%) three drugs (P<0.001). CONCLUSIONS: This study suggests that two-drug NPEP regimens do not result in excess seroconversions compared with three-drug regimens when used following RAIU. Clinical services should carefully consider their use of three drug NPEP and whether resources might be better invested in other prevention strategies, particularly pre-exposure prophylaxis (PrEP).
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Fármacos Anti-HIV/administração & dosagem , Infecções por HIV/prevenção & controle , Homossexualidade Masculina , Vigilância da População , Profilaxia Pós-Exposição/métodos , Comportamento Sexual/estatística & dados numéricos , Adulto , Quimioterapia Combinada , Infecções por HIV/epidemiologia , Humanos , Masculino , Sistema de Registros , Resultado do Tratamento , Vitória/epidemiologiaRESUMO
BACKGROUND: Completion rates for human immunodeficiency virus (HIV) postexposure prophylaxis (PEP) are low. We investigated the adherence and safety of coformulated emtricitabine (FTC), rilpivirine (RPV), and tenofovir disoproxil fumarate (TDF) as a 3-drug, single-tablet regimen for PEP in men who have sex with men (MSM). METHODS: In an open-label, single-arm study at 2 public sexual health clinics and 2 hospital emergency departments in urban Australia, 100 HIV-uninfected MSM requiring 3-drug PEP received single-tablet FTC-RPV-TDF once daily for 28 days. The primary endpoint was premature PEP cessation or primary HIV infection through week 12. Additional endpoints were adherence (by self-report of doses missed or not ingested with a meal, by pill count, and by plasma concentrations of tenofovir and FTC at week 4); and safety (clinical and laboratory adverse events [AEs]). RESULTS: PEP completion was 92% (95% confidence interval, 85%-96%); premature cessation resulted from loss to follow-up (6%), AEs (1%), or study burden (1%). No participant was found to acquire HIV through week 12. Adherence was 98.6% (standard deviation [SD], 2.4) by pill count and 98.5% (SD, 2.7) by self-report; 86% reported taking all doses with food, and 88% of the subset tested had plasma tenofovir levels suggesting full adherence (>40 ng/mL). Eighty-eight participants experienced at least 1 clinical AE; 4 had grade 3 AEs or higher, possibly attributable to study drug. Fifty-six participants experienced at least 1 laboratory AE; 4 had AEs of grade 3 or higher, possibly attributable to study drug. CONCLUSIONS: A single-tablet regimen of FTC-RPV-TDF was well tolerated as once-daily PEP, with high levels of adherence and completion. CLINICAL TRIALS REGISTRATION: NCT01715636.
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Fármacos Anti-HIV/administração & dosagem , Combinação Emtricitabina, Rilpivirina e Tenofovir/administração & dosagem , Infecções por HIV/prevenção & controle , Homossexualidade Masculina , Profilaxia Pós-Exposição , Adulto , Fármacos Anti-HIV/sangue , Fármacos Anti-HIV/uso terapêutico , Austrália , Esquema de Medicação , Combinação Emtricitabina, Rilpivirina e Tenofovir/sangue , Combinação Emtricitabina, Rilpivirina e Tenofovir/uso terapêutico , Humanos , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Comprimidos , Adulto JovemRESUMO
OBJECTIVE: To develop a guideline for the management of potential exposures to hepatitis B virus (HBV) at The Alfred Hospital, based on results of clinical audit, database analysis and literature review. METHODS: i) Retrospective record review of all histories of patients who received HBV immunoglobulin (HBIG) at The Alfred between 1/1/2007 and 30/9/2011. ii) Analysis of HBV serological results of men who have sex with men (MSM) on Victorian NPEP Service (VNPEPS) database between 10/8/2005 and 31/12/2011. iii) Literature review to determine risks of HBV transmission and best practice for prevention of HBV transmission. RESULTS: A total of 48 patients were potentially exposed to HBV and given HBIG, with sexual exposure the most common indication (n=20). The source was reported to be HBsAg positive in one case only. Of the MSM on the VNPEPS database, 63% were immune to HBV, and only 0.5% of patients tested had evidence of chronic HBV infection. The recommendations for use of HBIG in The Australian Immunisation Guidelines are ambiguous and differ from other international guidelines. CONCLUSION: This audit at a tertiary referral hospital identified problems with the management of those potentially exposed to HBV. In those non-immune patients exposed to HBV, the combination of HBIG plus vaccination provides the best protection against infection. The risk of transmission of HBV is highly variable; rates of chronic HBV in PWID and MSM in Australia are low and do not warrant use of HBIG unless the source is known to be HBsAg positive.
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Guias como Assunto , Vacinas contra Hepatite B/administração & dosagem , Hepatite B/diagnóstico , Hepatite B/prevenção & controle , Hepatite B/transmissão , Imunoglobulinas/administração & dosagem , Austrália , Medicina Baseada em Evidências , Feminino , Antígenos de Superfície da Hepatite B/sangue , Vírus da Hepatite B , Humanos , Masculino , Auditoria Médica , Estudos Retrospectivos , Centros de Atenção TerciáriaRESUMO
BACKGROUND: Human immunodeficiency virus (HIV)-infected patients on combination active antiretroviral therapy (cART) are at increased risk of age-related complications. We hypothesized that nucleos(t)ide reverse transcriptase inhibitors (NRTI) may contribute to accelerated aging in HIV-infected individuals on cART via inhibition of telomerase activity. METHODS: Telomerase activity and telomere length (TL) were measured by quantitative polymerase chain reaction in vitro in activated peripheral blood mononuclear cells (PBMCs) cultured with NRTI and ex vivo in PBMCs from uninfected patients exposed to NRTI and from HIV-infected patients on NRTI-containing cART. RESULTS: Lamivudine, abacavir, zidovudine, emtricitabine, and tenofovir significantly inhibited telomerase activity in activated PBMCs in vitro. Tenofovir was the most potent inhibitor of telomerase activity and caused greatest shortening of TL in vitro at the therapeutic concentration of 0.3 µM. PBMCs from HIV-infected patients receiving NRTI-containing cART (n = 39) had significantly lower telomerase activity than HIV-uninfected patients (n = 47; P = .011) and HIV-infected patients receiving non-NRTI-containing cART (n = 11; P < .001). TL was significantly inversely associated with age (P = .009) and the total duration on any NRTI (P = .01). CONCLUSIONS: NRTIs and, specifically tenofovir at therapeutic concentrations, inhibit telomerase activity leading to accelerated shortening of TL in activated PBMCs. The relationship between NRTI, reduced telomerase activity, and accelerated aging requires further investigation in HIV-infected individuals on cART.
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Adenina/análogos & derivados , Envelhecimento/efeitos dos fármacos , Fármacos Anti-HIV/efeitos adversos , Infecções por HIV/tratamento farmacológico , Organofosfonatos/efeitos adversos , Inibidores da Transcriptase Reversa/efeitos adversos , Telomerase/antagonistas & inibidores , Adenina/efeitos adversos , Adulto , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Estudos de Casos e Controles , Células Cultivadas , Desoxicitidina/efeitos adversos , Desoxicitidina/análogos & derivados , Didesoxinucleosídeos/efeitos adversos , Emtricitabina , Ativação Enzimática/efeitos dos fármacos , Feminino , HIV/patogenicidade , Infecções por HIV/patologia , Infecções por HIV/virologia , Humanos , Lamivudina/efeitos adversos , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/enzimologia , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Análise de Regressão , Fatores de Risco , Telomerase/metabolismo , Telômero/efeitos dos fármacos , Telômero/enzimologia , Encurtamento do Telômero , Tenofovir , Fatores de Tempo , Adulto Jovem , Zidovudina/efeitos adversosRESUMO
BACKGROUND: Despite widespread prescription of non-occupational post-exposure prophylaxis (NPEP) in Victoria, little is known about subsequent HIV acquisition among NPEP users. We linked the Victorian NPEP Service (VNPEPS) database and the Victorian HIV Surveillance Registry to determine the number, incidence rate and predictive factors of HIV seroconversions among users of the VNPEPS. METHODS: Records from male patients that received NPEP in the VNPEPS database (n = 1420) between January 2001 and February 2008 were linked with all entries in the Victorian HIV Surveillance Registry up to May 2008. RESULTS: Sixty-one men who presented to the VNPEPS were identified as HIV seropositive; 16 of these were diagnosed at initial presentation for NPEP. The incidence of HIV seroconversion in males who were HIV seronegative at first presentation for NPEP was 1.27 (95% confidence interval 0.95-1.70) per 100 person-years. There was no association between HIV seroconversion and number of NPEP presentations or age. The median age of seroconversion was 34.6 years. CONCLUSION: The incidence of HIV infection among men presenting to the VNPEPS is slightly lower than the HIV incidence in NPEP users in a recent Australian cohort study of men who have sex with men, but higher than HIV incidence in general gay male populations. Frequency of NPEP use was not associated with risk of HIV seroconversion. Examination of risk behaviour before and after NPEP use in this population is required to further assess the impact of NPEP availability and use on HIV incidence rates and risk behaviour in Australia.