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1.
Medicine (Baltimore) ; 100(12): e25110, 2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33761674

RESUMO

ABSTRACT: Oral direct-acting antiviral (DAA) treatment leads to >95% sustained virological response (SVR) and could be clinically useful in regression of liver fibrosis in chronic hepatitis C virus (HCV) infection. We evaluated if ledipasvir/sofosbuvir or sofosbuvir + ribavirin is associated with regression of fibrosis in HCV patients who achieved SVR.In this prospective cohort study performed at 3 sites in Japan, patients with genotype 1 and genotype 2 were given standard treatment of ledipasvir 90 mg/sofosbuvir 400 mg and sofosbuvir 400 mg + 200-1000 mg/day ribavirin, respectively, for 12 weeks. Liver fibrosis was assessed using Mac-2-binding protein glycosylation isomer (M2BPGi) and other fibrosis markers (platelet count, Fib-4 index, liver stiffness measurement [LSM]) in patients who achieved SVR.A total of 98.1% of (n = 101/103) patients in genotype 1 cohort and 100% (n = 16/16) in the genotype 2 cohort achieved SVR12. Based on per-protocol analysis, M2BPGi levels showed a significant decrease (-2.2  cut-off index [COI], P < .0001) at week 48 after treatment initiation. Forty-three patients showed a significant decrease in Fib-4 index (-1.2, P < .0001), and 44 patients showed improvement in LSM (-5.9 kPa, P < .0001).Achievement of SVR after antiviral therapy was associated with fibrosis regression. M2BPGi correlated well with LSM at week 48 after treatment initiation, supporting the sustainable benefit of HCV therapy.


Assuntos
Benzimidazóis/administração & dosagem , Fluorenos/administração & dosagem , Hepacivirus/efeitos dos fármacos , Hepatite C Crônica/tratamento farmacológico , Cirrose Hepática/tratamento farmacológico , Ribavirina/administração & dosagem , Sofosbuvir/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Combinada , Feminino , Hepatite C Crônica/complicações , Humanos , Fígado/efeitos dos fármacos , Fígado/virologia , Cirrose Hepática/virologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resposta Viral Sustentada , Resultado do Tratamento
2.
BMC Infect Dis ; 21(1): 239, 2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33673828

RESUMO

BACKGROUND: Hepatitis C Virus (HCV) is a leading cause for chronic liver diseases worldwide. The European Union and World Health Organization aspire to eliminate HCV by 2030. However, among at-risk populations, including, homeless people, prisoners and People Who Inject Drugs, access to diagnosis and treatment is challenging. Hepcare Europe is an integrated model of care developed to address this by assessing potential reasons for these restrictions and determining measures needed to improve HCV diagnosis, treatment and access to care within different communities. OBJECTIVES: HepCare Europe is an EU-supported project involving collaboration between five institutions in: Ireland, United Kingdom, Spain and Romania. We aim to explore the journey of care experienced by those living with HCV with a focus on previous care disruptions (loss to follow up) and the new HepCare Europe Programme. METHODS: Research teams conducted semi-structured interviews with patients who accessed services through HepCare Europe thus, patients were recruited by purposeful sampling. Patients interviewed had received, or were in the final weeks of receiving, treatment. The interviews were audio recorded, transcribed and translated into English, and sent to the Dublin team for inductive thematic analysis. Researchers from the HepCare Europe research team coded the data separately, then together. RESULTS: Common themes are introduced to present similarities, following individual site themes to highlight the importance of tailored interventions for each country. Key themes are: 1) Hepatitis C patients lost to follow up 2) HepCare improved access to treatment and 3) the need for improved HCV education. Individual themes also emerged for each site. These are: Ireland: New opportunities associated with achieving Sustained Virologic Responses (SVR). Romania: HCV is comparatively less crucial in light of Human Immunodeficiency Viruses (HIV) coinfections. UK: Patients desire support to overcome social barriers and Spain: Improved awareness of HCV, treatment and alcohol use. CONCLUSION: This study identified how the tailored HepCare interventions enabled improved HCV testing and linkage to care outcomes for these patients. Tailored interventions that targeted the needs of patients, increased the acceptability and success of treatment by patients. HepCare demonstrated the need for flexibility in treatment delivery, and provided additional supports to keep patients engaged and educated on new treatment therapies.


Assuntos
Assistência à Saúde , Hepatite C/diagnóstico , Hepatite C/terapia , Adulto , Usuários de Drogas , Europa (Continente) , Feminino , Hepacivirus , Pessoas em Situação de Rua , Humanos , Irlanda , Masculino , Pessoa de Meia-Idade , Prisioneiros , Romênia , Espanha , Resposta Viral Sustentada , Reino Unido
4.
Lancet Glob Health ; 9(4): e431-e445, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33639097

RESUMO

BACKGROUND: Increasing access to hepatitis C virus (HCV) care and treatment will require simplified service delivery models. We aimed to evaluate the effects of decentralisation and integration of testing, care, and treatment with harm-reduction and other services, and task-shifting to non-specialists on outcomes across the HCV care continuum. METHODS: For this systematic review and meta-analysis, we searched PubMed, Embase, WHO Global Index Medicus, and conference abstracts for studies published between Jan 1, 2008, and Feb 20, 2018, that evaluated uptake of HCV testing, linkage to care, treatment, cure assessment, and sustained virological response at 12 weeks (SVR12) in people who inject drugs, people in prisons, people living with HIV, and the general population. Randomised controlled trials, non-randomised studies, and observational studies were eligible for inclusion. Studies with a sample size of ten or less for the largest denominator were excluded. Studies were categorised according to the level of decentralisation: full (testing and treatment at same site), partial (testing at decentralised site and referral elsewhere for treatment), or none. Task-shifting was categorised as treatment by specialists or non-specialists. Data on outcomes across the HCV care continuum (linkage to care, treatment uptake, and SVR12) were pooled using random-effects meta-analysis. FINDINGS: Our search identified 8050 reports, of which 132 met the eligibility criteria, and an additional ten reports were identified from reference citations and grey literature. Therefore, the final synthesis included 142 studies from 34 countries (20 [14%] studies from low-income and middle-income countries) and a total of 489 996 patients (239 446 [49%] from low-income and middle-income countries). Rates of linkage to care were higher with full decentralisation compared with partial or no decentralisation among people who inject drugs (full 72% [95% CI 57-85] vs partial 53% [38-67] vs none 47% [11-84]) and among people in prisons (full 94% [79-100] vs partial 50% [29-71]), although the CIs overlap for people who inject drugs. Similarly, treatment uptake was higher with full decentralisation compared with partial or no decentralisation (people who inject drugs: full 73% [65-80] vs partial 66% [55-77] vs none 35% [23-48]; people in prisons: full 72% [48-91] vs partial 39% [17-63]), although CIs overlap for full versus partial decentralisation. The results in the general population studies were more heterogeneous. SVR12 rates were high (≥90%) across different levels of decentralisation in all populations. Task-shifting of care and treatment to a non-specialist was associated with similar SVR12 rates to treatment delivered by specialists. There was a severe or critical risk of bias for 46% of studies, and heterogeneity across studies tended to be very high (I2>90%). INTERPRETATION: Decentralisation and integration of HCV care to harm-reduction sites or primary care showed some evidence of improved access to testing, linkage to care, and treatment, and task-shifting of care and treatment to non-specialists was associated with similarly high cure rates to care delivered by specialists, across a range of populations and settings. These findings provide support for the adoption of decentralisation and task-shifting to non-specialists in national HCV programmes. FUNDING: Unitaid.


Assuntos
Prestação Integrada de Cuidados de Saúde/organização & administração , Acesso aos Serviços de Saúde/organização & administração , Hepatite C/diagnóstico , Hepatite C/tratamento farmacológico , Modelos Organizacionais , Antivirais/uso terapêutico , Prestação Integrada de Cuidados de Saúde/estatística & dados numéricos , Acesso aos Serviços de Saúde/estatística & dados numéricos , Hepacivirus/isolamento & purificação , Humanos , Programas Nacionais de Saúde/organização & administração , Programas Nacionais de Saúde/estatística & dados numéricos , Estudos Observacionais como Assunto , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Ensaios Clínicos Controlados Aleatórios como Assunto , Resposta Viral Sustentada
5.
AIDS Patient Care STDS ; 35(2): 39-46, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33571047

RESUMO

Viral suppression and postpartum retention in care have far-reaching health implications for pregnant women living with HIV and their children, yet remain public health challenges. Prenatal care presents a unique opportunity to engage pregnant women in care. The purpose of this study is to evaluate whether group prenatal care is effective in impacting these outcomes for pregnant women living with HIV. A retrospective cohort study was performed of all women living with HIV who obtained prenatal care from a community-based health center between 2013 and 2019. Women who spoke English or Spanish, remained within the system, and had not participated in group prenatal care previously were included. Women self-selected a prenatal care model: 85 selected group care and 109 elected individual care. Group prenatal care followed a standard Centering Pregnancy® curriculum with the addition of HIV-related topics. The primary outcomes of the study were viral suppression (viral load <20 copies/mL) and postpartum retention in care (attending at least one or two visits with HIV primary care within 12 months postpartum). After adjusting for potential confounding factors, women who participated in group prenatal care were significantly more likely to have at least one HIV primary care visit postpartum {adjusted odds ratio (aOR) = 2.71 [95% confidence interval (CI 1.14-6.46)]; p = 0.024}, and had a trend for achieving viral suppression by the time of delivery [aOR = 2.29 (95% CI 0.94-5.55); p = 0.068]. We have demonstrated that group prenatal care for pregnant women living with HIV is feasible and effective, with positive impacts on retention in care and viral suppression, factors that affect long-term outcomes from patients living with HIV.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Serviços de Saúde Comunitária/organização & administração , Infecções por HIV/tratamento farmacológico , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Complicações Infecciosas na Gravidez/tratamento farmacológico , Retenção nos Cuidados , Adulto , Criança , Estudos de Coortes , Centros Comunitários de Saúde , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/virologia , Humanos , Cuidado Pós-Natal , Período Pós-Parto , Gravidez , Complicações Infecciosas na Gravidez/epidemiologia , Gestantes , Cuidado Pré-Natal , Estudos Retrospectivos , Resposta Viral Sustentada , Texas/epidemiologia , Carga Viral
6.
Acta Gastroenterol Belg ; 84(1): 25-32, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33639690

RESUMO

Background and study aims: Cirrhosis associated to chronic hepatitis C virus (HCV) is one of the leading cause of hepatocellular carcinoma (HCC). The goal of our study was to evaluate first the risk and determinants of HCC and second the evolution of fibrosis in patients treated for HCV with advanced fibrosis stages who achieved sustained virological response (SVR) after direct-acting antivirals (DAA) treatment. Patients and methods: We conducted a prospective study on HCV patients with F3 or F4 Metavir fibrosis scores treated with DAA between October 2014 and February 2017. The annual incidence rate for HCC was calculated. We used Cox regression model in order to identify factors associated with HCC. Transient elastography (TE) was performed 12 and 24 months after the end of DAA treatment and non-invasive liver fibrosis biomarkers were performed twice a year during follow-up. Results: 143 patients with severe fibrosis or cirrhosis were enrolled in the study. 6 patients developed HCC. The annual incidence rate of HCC in our cohort was 2.7 per 100 patients. Risk factors associated with HCC after DAA were genotype 2 and steatosis. Overall TE values significantly decreased after DAA treatment with a median value prior to treatment of 16.9 kPa to a median of 10.8 kPa 24 months after the end of the treatment. Biological fibrosis scores also significantly decreased following viral eradication. Conclusions: DAA treatment does not seem to be associated with HCC promotion after HCV eradication in patients with severe fibrosis stages. DAA-induced SVR is associated with a reduced estimation of fibrosis.


Assuntos
Carcinoma Hepatocelular , Hepatite C Crônica , Hepatite C , Neoplasias Hepáticas , Antivirais/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/etiologia , Hepatite C/tratamento farmacológico , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Humanos , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/epidemiologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/etiologia , Estudos Prospectivos , Resposta Viral Sustentada
7.
BMC Infect Dis ; 21(1): 60, 2021 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-33435861

RESUMO

BACKGROUND: Little evidence exists to comprehensively estimate adolescent viral suppression after initiation on antiretroviral therapy in sub-Saharan Africa. This study examines adolescent progression along the HIV care cascade to viral suppression for adolescents initiated on antiretroviral therapy in South Africa. METHODS: All adolescents ever initiated on antiretroviral therapy (n=1080) by 2015 in a health district of the Eastern Cape, South Africa, were interviewed in 2014-2015. Clinical records were extracted from 52 healthcare facilities through January 2018 (including records in multiple facilities). Mortality and loss to follow-up rates were corrected for transfers. Predictors of progression through the HIV care cascade were tested using sequential multivariable logistic regressions. Predicted probabilities for the effects of significant predictors were estimated by sex and mode of infection. RESULTS: Corrected mortality and loss to follow-up rates were 3.3 and 16.9%, respectively. Among adolescents with clinical records, 92.3% had ≥1 viral load, but only 51.1% of viral loads were from the past 12 months. Adolescents on ART for ≥2 years (AOR 3.42 [95%CI 2.14-5.47], p< 0.001) and who experienced decentralised care (AOR 1.39 [95%CI 1.06-1.83], p=0.018) were more likely to have a recent viral load. The average effect of decentralised care on recent viral load was greater for female (AOR 2.39 [95%CI 1.29-4.43], p=0.006) and sexually infected adolescents (AOR 3.48 [95%CI 1.04-11.65], p=0.043). Of the total cohort, 47.5% were recorded as fully virally suppressed at most recent test. Only 23.2% were recorded as fully virally suppressed within the past 12 months. Younger adolescents (AOR 1.39 [95%CI 1.06-1.82], p=0.017) and those on ART for ≥2 years (AOR 1.70 [95%CI 1.12-2.58], p=0.013) were more likely to be fully viral suppressed. CONCLUSIONS: Viral load recording and viral suppression rates remain low for ART-initiated adolescents in South Africa. Improved outcomes for this population require stronger engagement in care and viral load monitoring.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , HIV-1/genética , Adolescente , Criança , Continuidade da Assistência ao Paciente , Feminino , Seguimentos , Infecções por HIV/mortalidade , Infecções por HIV/virologia , Humanos , Modelos Logísticos , Estudos Longitudinais , Masculino , RNA Viral/genética , Estudos Retrospectivos , África do Sul/epidemiologia , Resposta Viral Sustentada , Carga Viral/efeitos dos fármacos , Adulto Jovem
8.
Am J Gastroenterol ; 116(3): 576-583, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33399360

RESUMO

INTRODUCTION: Despite recognized differences in the rates of cardiovascular and renal disease between men and women in the general population, studies of the downstream effects of antiviral treatment for hepatitis C (HCV) have not investigated differences in outcomes based on sex. We analyzed sex differences in risk of acute coronary syndrome (ACS), end-stage renal disease (ESRD), and ischemic stroke by treatment and response in a large US-based multisite cohort of HCV patients. METHODS: Observation started at the HCV diagnosis date (untreated) or last antiviral treatment start (treated). Treatment selection bias was addressed using an inverse probability-weighting approach. We estimated the effect of treatment on the cumulative incidence of outcomes using the Fine-Gray method (subdistribution hazard ratios [sHR] and 95% confidence intervals [95% CI]). Death was a competing risk. RESULTS: Roughly 40% of 15,295 HCV patients were women. After controlling for other risk factors, sustained virological response (SVR) (interferon-based [IFN] or direct-acting antiviral [DAA]) significantly reduced risk of all outcomes, particularly among female patients. Female patients who achieved SVR after IFN-based treatment had significantly lower risk of ACS compared with male patients with SVR from either treatment type (sHR 0.45 [95% CI 0.35-0.59] vs 0.81 [95% CI 0.69-0.96, for DAA SVR] and sHR 0.72 [95% 0.62, 0.85, for IFN SVR]). Successful treatment seemed to be most protective against ESRD; female patients who achieved SVR were at 66%-68% lower risk than untreated patients (sHR 0.32 [95% CI 0.17-0.60 for DAA SVR] and 0.34 [95% CI 0.20-0.58 for IFN SVR]), whereas men were at 38%-42% lower risk (sHR 0.62 [95% CI 0.46-0.85 for DAA SVR] and 0.58 [95% CI 0.43-0.76 for IFN SVR]). IFN treatment failure significantly increased risk of all outcomes by 50%-100% among female patients. Compared with no treatment, female patients who experienced IFN treatment failure were at 63% increased risk of ACS (sHR 1.63 [95% CI 1.35-1.96]), almost twice the risk of ESRD (sHR 1.95 [95% CI 1.43-2.66]) and 51% increased risk of stroke (sHR 1.49 [95%CI 1.11-2.00]). DISCUSSION: SVR reduced the risk of extrahepatic complications, particularly in females. The significantly increased risk associated with IFN TF in women-a subset who represented roughly 10% of that group-underscores the importance of prioritizing these patients for DAA treatment irrespective of the fibrosis stage.


Assuntos
Síndrome Coronariana Aguda/epidemiologia , Antivirais/uso terapêutico , Hepatite C/tratamento farmacológico , Falência Renal Crônica/epidemiologia , Síndrome Coronariana Aguda/virologia , Feminino , Hepatite C/complicações , Humanos , Incidência , Falência Renal Crônica/virologia , Masculino , Pessoa de Meia-Idade , Risco , Fatores Sexuais , Resposta Viral Sustentada , Resultado do Tratamento
9.
Afr J AIDS Res ; 19(4): 304-311, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33337979

RESUMO

Background: The human immunodeficiency virus (HIV) pandemic increased the demand for health care resources in South Africa. To decrease the burden on specialised facilities, the Department of Health decentralised antiretroviral (ARV) management. In the uMgungundlovu district, adult HIV primary care services reported lower rates of HIV viral load (VL) suppression after initiation of ARVs compared to other levels of care. The aim of the study was to evaluate paediatric HIV services in the same district. Methods: Four ARV clinics, at different levels of care, initiating and monitoring paediatric HIV infection treatment in uMgungundlovu district, KwaZulu Natal, were selected: primary healthcare services, general practitioner services, general paediatric services and subspecialist infectious diseases services were included. Paediatric patients newly diagnosed between January 2014 and June 2015 were included in the study. The rate of HIV VL suppression at one year after treatment initiation was the primary outcome measure. A total of 377 patients were included, 35 at the nurse-led primary care clinic, 25 at the general practitioner-led primary care clinic, 156 at the paediatrician-led secondary care clinic, and 161 at the HIV paediatric subspecialist-led tertiary care clinic. Of the 377 patients, 154 (59.9%) achieved VL suppression at one year, with 75% (18/24), 61.9% (13/21), 51.7% (60/116) and 66.7% (63/96) achieving HIV VL suppression at the four clinic types, respectively. Conclusion: HIV VL suppression rates were variable, but did not differ statistically across levels of health care. Outcomes were not improved by initiation in specialist or subspecialist-led clinics, which supports the strategy of increasing access by decentralising HIV care for paediatric patients.


Assuntos
Antirretrovirais/uso terapêutico , Assistência à Saúde/organização & administração , Infecções por HIV/tratamento farmacológico , Criança , Pré-Escolar , Assistência à Saúde/estatística & dados numéricos , Feminino , HIV/efeitos dos fármacos , Infecções por HIV/epidemiologia , Humanos , Lactente , Recém-Nascido , Masculino , Avaliação de Programas e Projetos de Saúde , África do Sul/epidemiologia , Resposta Viral Sustentada
10.
PLoS Negl Trop Dis ; 14(12): e0008931, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33326423

RESUMO

BACKGROUND: Despite direct-acting antivirals (DAA), aims to "eradicate" viral hepatitis by 2030 remain unlikely. In Nepal, an expert consortium was established to treat HCV through Nepal earthquakes aftermath offering a model for HCV treatment expansion in a resource-poor setting. METHODOLOGY/PRINCIPAL FINDINGS: In 2015, we established a network of hepatologists, laboratory experts, and community-based leaders at 6 Opioid Substitution Treatment (OST) sites from 4 cities in Nepal screening 838 patients for a treatment cohort of 600 individuals with HCV infection and past or current drug use. During phase 1, patients were treated with interferon-based regimens (n = 46). During phase 2, 135 patients with optimal predictors (HIV controlled, without cirrhosis, low baseline HCV viral load) were treated with DAA-based regimens. During phase 3, IFN-free DAA treatment was expanded, regardless of HCV disease severity, HIV viremia or drug use. Sustained virologic response (SVR) was assessed at 12 weeks. Median age was 37 years and 95.5% were males. HCV genotype was 3 (53.2%) or 1a (40.7%) and 32% had cirrhosis; 42.5% were HIV-HCV coinfected. The intention-to-treat (ITT) SVR rates in phase 2 and 3 were 97% and 81%, respectively. The overall per-protocol and ITT SVR rates were 97% and 85%, respectively. By multivariable analysis, treatment at the Kathmandu site was protective and substance use, treatment during phase 3 were associated with failure to achieve SVR. CONCLUSIONS/SIGNIFICANCE: Very high SVR rates may be achieved in a difficult-to-treat, low-income population whatever the patient's profile and disease severity. The excellent treatment outcomes observed in this real-life community study should prompt further HCV treatment initiatives in Nepal.


Assuntos
Antivirais/uso terapêutico , Infecções por HIV/complicações , Hepacivirus/efeitos dos fármacos , Hepatite C/tratamento farmacológico , Interferons/uso terapêutico , Cirrose Hepática/complicações , Adulto , Coinfecção , Quimioterapia Combinada , Feminino , Hepatite C/complicações , Hepatite C/virologia , Humanos , Cirrose Hepática/virologia , Masculino , Nepal , Resposta Viral Sustentada , Resultado do Tratamento
11.
BMC Infect Dis ; 20(1): 836, 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33176715

RESUMO

BACKGROUND: The KwaZulu-Natal (KZN) province of South Africa has the highest prevalence of HIV infection in the world. Viral load (VL) testing is a crucial tool for clinical and programmatic monitoring. Within uMkhanyakude district, VL suppression rates were 91% among patients with VL data; however, VL performance rates averaged only 38·7%. The objective of this study was to determine if enhanced clinic processes and community outreach could improve VL monitoring within this district. METHODS: A packaged intervention was implemented at three rural clinics in the setting of the KZN HIV AIDS Drug Resistance Surveillance Study. This included file hygiene, outreach, a VL register and documentation revisions. Chart audits were used to assess fidelity. Outcome measures included percentage VL performed and suppressed. Each rural clinic was matched with a peri-urban clinic for comparison before and after the start of each phase of the intervention. Monthly sample proportions were modelled using quasi-likelihood regression methods for over-dispersed binomial data. RESULTS: Mkuze and Jozini clinics increased VL performance overall from 33·9% and 35·3% to 75·8% and 72·4%, respectively which was significantly greater than the increases in the comparison clinics (RR 1·86 and 1·68, p < 0·01). VL suppression rates similarly increased overall by 39·3% and 36·2% (RR 1·84 and 1·70, p < 0·01). The Chart Intervention phase showed significant increases in fidelity 16 months after implementation. CONCLUSIONS: The packaged intervention improved VL performance and suppression rates overall but was significant in Mkuze and Jozini. Larger sustained efforts will be needed to have a similar impact throughout the province.


Assuntos
Síndrome de Imunodeficiência Adquirida/epidemiologia , Monitoramento Epidemiológico , HIV-1/genética , Saúde da População Rural , Carga Viral/métodos , Síndrome de Imunodeficiência Adquirida/tratamento farmacológico , Síndrome de Imunodeficiência Adquirida/virologia , Adulto , Antirretrovirais/uso terapêutico , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , População Rural , África do Sul/epidemiologia , Resposta Viral Sustentada , Carga Viral/efeitos dos fármacos
12.
PLoS One ; 15(10): e0239190, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33001986

RESUMO

BACKGROUND: People with HIV with co-occurring substance use and mental health diagnoses who are unstably housed have poorer outcomes for retention in care and viral suppression. Navigation models are a potential strategy to help this vulnerable population obtain the necessary medical and non-medical services across multiple service systems. The Health Resources and Services Administration's Special Projects of National Significance: "Building a Medical Home for Multiply-Diagnosed HIV-positive Homeless Populations initiative 2012-2017 found that navigation models may be an effective intervention to support people with HIV with unstable housing improve HIV health outcomes. However, there is limited information about the mechanisms by which this intervention works. In this article, we explore the participant and program factors for achieving stable housing at 6 months and how these factors influence HIV health outcomes. METHODS AND FINDINGS: This was a prospective study of 471 unstably housed people with HIV enrolled in a navigation intervention across nine sites in the United Stated from 2013-2017. All sites provided HIV primary medical care. Eight sites were located in urban areas and one site served a predominantly rural population. Two sites were federally qualified health centers, three were city or county health departments, one site was a comprehensive HIV/AIDS service organization, and three sites were outpatient or mobile clinics affiliated with a university -based or hospital system. Data were collected via interview and medical chart review at baseline, post 6 and 12 months. Type and dose of navigation activities were collected via a standardized encounter form. We used a path analysis model with housing stability at 6 months as the mediator to examine the direct and indirect effects of participant's socio-demographics and risk factors and navigation on viral suppression and retention in care at 12 months. Housing stability at 6 months was associated with male gender, younger age, viral suppression at baseline, having a lower risk for opiate use, recent homelessness, lower risk of food insecurity, and a longer length of time living with HIV. Participants who increased self-efficacy with obtaining help by 6 months had significantly higher odds of achieving housing stability. Stable housing, fewer unmet needs, moderate to high risk for opiate use, and viral suppression at baseline had a direct effect on viral suppression at 12 months. The intensity of navigation contact had no direct effect on housing stability and a mixed direct effect on viral suppression. Recent diagnosis with HIV, women, greater social support, increased self-efficacy and higher intensity of navigation contact had a direct effect on improved retention in HIV primary care at 12 months. CONCLUSIONS: In this sample of people with HIV who are experiencing homelessness, housing stability had a significant direct path to viral suppression. Navigation activities did not have a direct effect on the path to housing stability but were directly related to retention in care. These results identify key populations and factors to target resources and policies for addressing the health and social unmet needs of people with HIV to achieve housing stability and HIV health outcomes.


Assuntos
Infecções por HIV/terapia , Pessoas em Situação de Rua , Habitação , Assistência Centrada no Paciente , Adulto , Feminino , Infecções por HIV/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Navegação de Pacientes , Assistência Centrada no Paciente/organização & administração , Estudos Prospectivos , Retenção nos Cuidados , Apoio Social , Resposta Viral Sustentada , Estados Unidos
13.
BMC Infect Dis ; 20(1): 727, 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33023498

RESUMO

BACKGROUND: Viral load (VL) testing is the gold-standard approach for monitoring human immunodeficiency virus (HIV) treatment success and virologic failure, but uptake is suboptimal in resource-limited and rural settings. We conducted a cross-sectional study of risk factors for non-uptake of VL testing in rural Uganda. METHODS: We conducted a cross-sectional analysis of uptake of VL testing among randomly selected people with HIV (PWH) receiving anti-retroviral treatment (ART) for at least 6 months at all eight primary health centers in Gomba district, rural Uganda. Socio-demographic and clinical data were extracted from medical records for the period January to December 2017. VL testing was routinely performed 6 months after ART initiation and 12 months thereafter for PWH stable on ART. We used descriptive statistics and multivariable logistic regression to evaluate factors associated with non-uptake of VL testing (the primary outcome). RESULTS: Of 414 PWH, 60% were female, and the median age was 40 years (interquartile range [IQR] 31-48). Most (62.3%) had been on ART > 2 years, and the median duration of treatment was 34 months (IQR 14-55). Thirty three percent did not receive VL testing: 36% of women and 30% of men. Shorter duration of ART (≤2 years) (adjusted odds ratio [AOR] 2.38; 95% CI:1.37-4.12; p = 0.002), younger age 16-30 years (AOR 2.74; 95% CI:1.44-5.24; p = 0.002) and 31-45 years (AOR 1.92; 95% CI 1.12-3.27; p = 0.017), and receipt of ART at Health Center IV (AOR 2.85; 95% CI: 1.78-4.56; p < 0.001) were significantly associated with non-uptake of VL testing. CONCLUSIONS: One-in-three PWH on ART missed VL testing in rural Uganda. Strategies to improve coverage of VL testing, such as VL focal persons to flag missed tests, patient education and demand creation for VL testing are needed, particularly for recent ART initiates and younger persons on treatment, in order to attain the third Joint United Nations Program on HIV/AIDS (UNAIDS) 95-95-95 target - virologic suppression for 95% of PWH on ART.


Assuntos
Antirretrovirais/uso terapêutico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , HIV-1/imunologia , População Rural , Carga Viral/efeitos dos fármacos , Adolescente , Adulto , Criança , Pré-Escolar , Estudos Transversais , Feminino , Infecções por HIV/virologia , Humanos , Lactente , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fatores de Risco , Testes Sorológicos , Resposta Viral Sustentada , Uganda/epidemiologia , Adulto Jovem
14.
Medicine (Baltimore) ; 99(40): e22435, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33019424

RESUMO

Given that evidence supporting chronic hepatitis C (CHC) infection developed chance for hepatocellular carcinoma (HCC) following antiviral agents therapy is controversial. We conducted a meta-analysis to examine the risk.We evaluated 20 retrospective and prospective cohort studies published up to 31 December 2017 which investigated the association between sustained virological response (SVR) and incidence of HCC patients treated with monotherapy interferon (IFN) or IFN plus ribavirin (RBV) therapy. The primary outcome of the study was the cumulative incidence of HCC. Odds ratio (OR) was used to evaluate the index of effect size for the association between SVR and treatment with IFN alone or IFN/RBV in CHC patients.SVR patients demonstrated a lower incidence of HCC compared to non-SVR patients. Non-SVR patients had greater odds of HCC incidence compared to SVR patients in the treatment of IFN plus RBV (pooled OR = 7.405, 95% CI = 4.689 to 11.694, P < .001). Non-SVR patients had greater odds of HCC incidence compared to SVR patients in the treatment of IFN monotherapy (pooled OR = 4.135, 95% CI = 3.009 to 5.682, P < .001). Lack of SVR to IFN therapy was significantly associated with greater risk of HCC incidence (pooled OR = 5.035, 95% CI = 3.915 to 6.474, P < .001).SVR could be as a predictor of HCC in CHC patients treated with IFN or IFN plus RBV, and have important implications during HCC screening, whereby patients who fail to achieve SVR need to be screened more rigorously.


Assuntos
Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Resposta Viral Sustentada , Carcinoma Hepatocelular/virologia , Feminino , Humanos , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Estudos Observacionais como Assunto
15.
Medicine (Baltimore) ; 99(42): e21972, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33080669

RESUMO

Treatment of hepatitis C virus (HCV) infection in patients with chronic kidney disease was difficult in the past because of the use of interferon (IFN). It was associated with high risk IFN-related adverse reactions due to reduced renal clearance of IFN. This study aimed to evaluate the antiviral efficacy, safety, and tolerability of ombitasvir/paritaprevir/ritonavir/ribavirin in chronic kidney disease patients infected with chronic HCV.This observational, open-label prospective study was carried out on 103 patients infected chronic HCV with different grades of renal impairment. Paritaprevir/ritonavir and ombitasvir (75/50/12.5 mg) twice daily plus ribavirin were given to the patients for 12 weeks. Dose adjustment of ribavirin was done according to degree of renal impairment.Sustained virological response (12 weeks after the end of treatment) occurred in 101 patients (98.1%). Anemia occurred in 48 patients. No serious adverse events were observed in any patient.Paritaprevir/ritonavir and ombitasvir plus ribavirin for 12 weeks was considered to be safe and effective in the treatment of chronic HCV infected patients with varying degrees of renal impairment.


Assuntos
Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Falência Renal Crônica/complicações , Adulto , Idoso , Anilidas/uso terapêutico , Carbamatos/uso terapêutico , Quimioterapia Combinada , Egito , Feminino , Humanos , Compostos Macrocíclicos/uso terapêutico , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Ribavirina/uso terapêutico , Ritonavir/uso terapêutico , Resposta Viral Sustentada
16.
BMC Infect Dis ; 20(1): 802, 2020 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-33121439

RESUMO

BACKGROUND: Safe, highly curative, short course, direct acting antiviral (DAA) therapies are now available to treat chronic hepatitis C. DAA therapy is freely available to all adults chronically infected with the hepatitis C virus (HCV) in Australia. If left untreated, hepatitis C may lead to progressive hepatic fibrosis, cirrhosis and hepatocellular carcinoma. Australia is committed to eliminating hepatitis as a public health threat by 2030 set by the World Health Organization. However, since the introduction of funded DAA treatment, uptake has been suboptimal. Australia needs improved strategies for testing, treatment uptake and treatment completion to address the persisting hepatitis C public health problem. PLATINUM C is a HCV treatment registry and research platform for assessing the comparative effectiveness of alternative interventions for achieving virological cure. METHODS: PLATINUM C will prospectively enrol people with active HCV infection confirmed by recent detection of HCV ribonucleic acid (RNA) in blood. Those enrolled will agree to allow standardised collection of demographic, lifestyle, treatment, virological outcome and other relevant clinical data to better inform the future management of HCV infection. The primary outcome is virological cure evidenced by sustained virological response (SVR), which is defined as a negative HCV PCR result 6 to 18 months after initial prescription of DAA therapy and no less than 12 weeks after the completion of treatment. Study participants will be invited to opt-in to medication adherence monitoring and quality of life assessments using validated self-reported instruments (EQ-5D-5L). DISCUSSION: PLATINUM C is a treatment registry and platform for nesting pragmatic trials. Data collected will inform the design, development and implementation of pragmatic trials. The digital infrastructure, study procedures and governing systems established by the registry will allow PLATINUM C to support a wider research platform in the management of hepatitis C in primary care. TRIAL REGISTRATION: The trial is registered with the Australia and New Zealand Clinical Trials Register ( ACTRN12619000023156 ). Date of registration: 10/01/2019.


Assuntos
Antivirais/uso terapêutico , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Sistema de Registros , Austrália/epidemiologia , Genótipo , Hepatite C Crônica/epidemiologia , Hepatite C Crônica/virologia , Humanos , Estilo de Vida , Cirrose Hepática/diagnóstico , Reação em Cadeia da Polimerase , Estudos Prospectivos , RNA Viral/sangue , RNA Viral/genética , Resposta Viral Sustentada
17.
AIDS ; 34(15): 2328-2331, 2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-32910069

RESUMO

: The COVID-19 pandemic is expected to hinder US End the HIV Epidemic goals. We evaluated viral suppression and retention-in-care before and after telemedicine was instituted, in response to shelter-in-place mandates, in a large, urban HIV clinic. The odds of viral nonsuppression were 31% higher postshelter-in-place (95% confidence interval = 1.08-1.53) in spite of stable retention-in-care and visit volume, with disproportionate impact on homeless individuals. Measures to counteract the effect of COVID-19 on HIV outcomes are urgently needed.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Controle de Doenças Transmissíveis , Infecções por Coronavirus/prevenção & controle , Assistência à Saúde , Infecções por HIV/tratamento farmacológico , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Política Pública , Resposta Viral Sustentada , Telemedicina , Adulto , Afro-Americanos , Fatores Etários , Betacoronavirus , Grupo com Ancestrais do Continente Europeu , Feminino , Infecções por HIV/sangue , Acesso aos Serviços de Saúde , Pessoas em Situação de Rua/estatística & dados numéricos , Humanos , Masculino , Pacientes não Comparecentes/estatística & dados numéricos , Razão de Chances , Retenção nos Cuidados/estatística & dados numéricos , Provedores de Redes de Segurança , São Francisco , Carga Viral
18.
PLoS One ; 15(9): e0232649, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32986709

RESUMO

Emergence of HIV drug resistance poses a serious risk of inactivity to all currently approved antiretroviral drugs. Profiles of HIV drug resistance mutations (HIVDRM) and virological failure (VF) are not extensively studied in Tanzania. This study aimed to determine HIVDRM and predictors of VF in HIV-infected individuals failing first-line HIV drugs in Moshi, Northern Tanzania. A case-control study was conducted at Kilimanjaro Christian Medical Centre, Mawenzi, Pasua and Majengo health facilities with HIV-care and treatment clinics from October, 2017 to August, 2018. Cases and controls were HIV-infected individuals with VF and viral suppression (VS) respectively. HIV-1 reverse transcriptase and protease genes were amplified and sequenced. Stanford University's HIV drug resistance database and REGA subtyping tool 3.0 determined HIVDRM and HIV-1 subtypes respectively. Odds ratios (OR) with 95% confidence interval (95% CI) investigated predictors of VF. P-value < 5% was considered statistically significant. A total of 124 participants were recruited, of whom 63 (50.8%) had VF, 61 (49.2%) had VS and 82 (66.1%) were females. Median [IQR] age and duration on ART were 45 [35-52] years and 72 [48-104] months respectively. Twenty-five out of 26 selected samples from cases were successfully sequenced. Twenty-four samples (96%) had at least one major mutation conferring resistance to HIV drugs, with non-nucleoside analogue reverse transcriptase inhibitor (NNRTI)-resistance associated mutations as the majority (92%). Frequent NNRTI-resistance associated mutations were K103N (n = 11), V106M (n = 5) and G190A (n = 5). Prevalent nucleoside analogue reverse transcriptase inhibitors-resistance associated mutations were M184V (n = 17), K70R (n = 7) and D67N (n = 6). Dual-class resistance was observed in 16 (64%) samples. Thirteen samples (52%) had at least one thymidine analogue-resistance associated mutation (TAM). Three samples (12%) had T69D mutation with at least 1 TAM. Two samples (8%) had at least one mutation associated with protease inhibitor resistance. Age [aOR = 0.94, 95% CI (0.90-0.97), p < 0.001] and occupation [aOR = 0.35, 95% CI (0.12-1.04), p = 0.059] associated with VF. In conclusion, HIV drug resistance is common among people failing antiretroviral therapy. Resistance testing will help to guide switching of HIV drugs.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Farmacorresistência Viral/genética , Infecções por HIV/tratamento farmacológico , HIV-1/genética , Falha de Tratamento , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Infecções por HIV/epidemiologia , HIV-1/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Resposta Viral Sustentada , Tanzânia/epidemiologia , Carga Viral/efeitos dos fármacos , Adulto Jovem
19.
Medicine (Baltimore) ; 99(38): e22362, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32957410

RESUMO

Cytokines are extensively involved in the process of hepatitis C virus (HCV) infection and take a crucial part in host immune regulation. We aimed to explore the potential correlation of cytokine single nucleotide polymorphisms (SNPs) with HCV susceptibility and response rate of interferon (IFN)-based antiviral therapy in Chinese Han population.A case-control genetic association study was conducted between 198 patients with chronic HCV genotype 1b infection and 142 healthy controls. Genetic polymorphisms of TNF-α (rs1800629), TGF-ß (rs1800469), IL-10 (rs1800896, rs1800871, and rs1800872), IL-6 (rs1800795, rs1800796), IFN-γ (rs2430561), and IL-28B (rs12979860, rs12980275, and rs8099917) were analyzed by MassARRAY SNP technology. Patients were treated with IFNα-2b or pegylated-IFNα-2a plus ribavirin for 48 weeks. Sustained virological response (SVR) was assessed 6 months after the completion of the treatment.The IL-28B rs12979860-CC (odds ratio [OR] = 4.35, 95% confidence interval [CI]: 1.69-11.21, P = .001), rs12980275-AA (OR = 3.41, 95% CI: 1.08-10.76, P = .028), and rs8099917-TT (OR = 3.86, 95% CI: 1.49-10.12, P = .004) were significantly associated with SVR, and IL-10 rs1800871-TT (OR = .50, 95% CI: 0.25-1.00, P = .049) and rs1800872-AA (OR = .50, 95% CI: 0.25-1.00, P = .049) were also significant for SVR. No association was found between the cytokine SNPs and HCV susceptibility. Additionally, multivariate analysis showed that low baseline viral load (OR = 3.63, 95% CI: 1.01-13.02, P = .048), pegylated-IFN (OR = 9.68, 95% CI: 1.14-82.13, P = .037) and rs12979860-CC (OR = 6.08, 95% CI: 2.00-18.46, P = .001) were independent factors for SVR.IL-28 and IL-10 gene polymorphisms played an important role in predicting host response to IFN-based antiviral therapy in HCV genotype 1b infection.


Assuntos
Citocinas/genética , Hepatite C Crônica/tratamento farmacológico , Resposta Viral Sustentada , Adulto , Idoso , Antivirais/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Estudos Prospectivos , Carga Viral/genética
20.
Arch Virol ; 165(12): 2759-2766, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32885325

RESUMO

Oxidative stress (OS) and insulin resistance (IR) induced by hepatitis C virus (HCV) infection, are involved in the development of chronic hepatitis C (CHC) complications and progression to hepatocellular carcinoma. The aim of this study was to investigate the effect of pegylated interferon alpha (IFNα) + ribavirin (PegIFNα+RVB) or sofosbuvir + NS5A inhibitor (SOF+InNS5A) on IR and the components of OS. HCV was genotyped in 20 CHC patients grouped by treatment with either PegIFNα+RVB (n = 10) or SOF+InNS5A (n = 10). The treatment's effect on OS-induced damage to lipids (HNE-HDL), proteins (advanced glycation end products [AGEs]), and DNA (8-OHdG) as well as the concentrations of proinflammatory cytokines (IL-2, TNFα, IFNγ), ALT, AST, GSH and platelets was determined. Superoxide dismutase (SOD) and catalase activity as well as IR, determined by the HOMA1-IR index, was evaluated. The HCV genotypes (GT) found were GT1b (45%), GT1a (30%), GT2b (20%), and GT2a (5%). Viral RNA became undetectable by week 12 with SOF+InNS5A in 100% of the cases and with PegIFNα+RVB in 70% of the cases. After viral RNA became undetectable, regardless of treatment and GT, a significant increase in the platelet concentration and SOD activity was observed, whereas ALT, insulin, and IR decreased (p < 0.05). However, only for the SOF+InNS5A treated group was there an increase in oxidative damage to lipids (p < 0.017) and proteins (p < 0.05). None of the other parameters demonstrated any differences. These data confirm that OS persisted after treatment with either SOF+InNS5A or PegIFNα+RVB. IR could be considered a response biomarker to treatment with direct-acting antivirals.


Assuntos
Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Resistência à Insulina , Estresse Oxidativo/efeitos dos fármacos , RNA Viral/isolamento & purificação , Adulto , Quimioterapia Combinada , Feminino , Genótipo , Hepacivirus/efeitos dos fármacos , Hepatite C Crônica/virologia , Humanos , Interferon-alfa/uso terapêutico , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Ribavirina/uso terapêutico , Sofosbuvir/uso terapêutico , Resposta Viral Sustentada , Resultado do Tratamento , Proteínas não Estruturais Virais/antagonistas & inibidores
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