Servicii medicale integrate pentru pacienții coinfectați HIV/VHC din România ce provin din populațiile marginalizate – modelul Proiectului HepCare Europe implementat la Spitalul „Dr. Victor Babeș“ din București

Background. Proiectul HepCare Europe, cofinanţat de Comisia Europeană, a avut ca scop crearea şi implementarea unui model de management al VHC (screening, evaluare şi tratament) adresat pacienţilor ce provin din populaţiile vulnerabile. Ideea de bază a proiectului a fost creşterea accesului acestor pacienţi la servicii medicale integrate, prin implicarea cadrelor medicale din comunitate. Scopul acestui studiu a fost să evalueze caracteristicile socio-demografice şi clinice ale pacienţilor coinfectaţi HIV/VHC comparativ cu cei monoinfectaţi cu VHC înrolaţi în Proiectul HepCare Europe, în cadrul Spitalului Clinic de Boli Infecţioase şi Tropicale „Dr. Victor Babeş“ din Bucureşti. Metode. Studiu prospectiv efectuat la pacienţii cu anticorpi anti-VHC pozitivi (prin teste rapide orale), ce au fost evaluaţi la Spitalul „Dr. Victor Babeş“ din Bucureşti, România (SVB), în perioada aprilie 2016 – aprilie 2019. Caracteristicile socio-demografice şi clinice ale pacienţilor au fost comparate în funcţie de statusul de coinfectat HIV. Analiza statistică a datelor s-a realizat folosind programul SPSS versiunea 20.0. Rezultate. Screening-ul pentru hepatita cronică cu virus C s-a realizat la 525 de pacienţi, dintre care 230 (43,8%) au avut rezultat pozitiv. Majoritatea erau tineri, de sex masculin (85,2%) şi utilizatori de droguri injectabile (92,2%). 168 de pacienţi (73,0%) au fost evaluaţi la spital, din care 41,6% erau coinfectaţi HIV. Evaluarea gradului de fibroză hepatică s-a realizat pentru 82,1% dintre pacienţi, aproape o treime fiind identificaţi cu fibroză hepatică avansată (27,5%). ARN-VHC în plasmă a fost efectuat pentru jumătate din pacienţii luaţi în evidenţă, 80,9% din aceştia având încărcătură virală detectabilă. 24 de pacienţi au iniţiat tratamentul cu agenţi antivirali direcţi, din care 22 au obţinut răspuns viral susţinut, iar 2 au fost nonresponderi (utilizatori de droguri infectaţi cu genotip 3 ce nu au primit tratament cu regim pangenotipic). Infecţia HIV s-a asociat cu lipsa locuinţei (p < 0,0001), consumul de droguri injectabile (p = 0,001), consumul de etnobotanice în asociere cu opioidele (p < 0,0001), utilizarea de ace la comun (p < 0,0001) sau consumul de alcool (p < 0,0001). Valoarea mediană a limfocitelor CD4 la diagnostic a fost de 483/µl (IQR 290, 646), iar valoarea mediană a încărcăturii virale HIV în plasmă a fost de 2.74 log10copii/ml (IQR 1,27, 4,67). Încărcătura virală VHC în plasmă a fost semnificativ mai mare la pacienţii coinfectaţi HIV/VHC (p = 0,047). Concluzii. Coinfecţia HIV/VHC a fost frecventă la pacienţii ce provin din populaţiile vulnerabile. Infecţia HIV a fost asociată cu multipli factori de risc şi încărcătură virală VHC plasmatică mai ridicată. Barierele socio-economice şi accesul redus la tratamente pangenotipice cu agenţi antivirali direcţi (DAA) au limitat semnificativ iniţierea tratamentului la aceşti pacienţi. Acesta este primul studiu pilot din România despre managementul pacienţilor cu hepatită C care provin din populaţiile cheie

Integrating primary and secondary care to optimize hepatitis C treatment:development and evaluation of a multidisciplinary educational Masterclass series

[Background] It is increasingly being recognized that the elimination of HCV requires a multidisciplinary approach and effective cooperation between primary and secondary care.[Objectives] As part of a project (HepCare Europe) to integrate primary and secondary care for patients at risk of or infected with HCV, we developed a multidisciplinary educational Masterclass series for healthcare professionals (HCPs) working in primary care in Dublin and Bucharest. This article aims to describe and evaluate the series and examine how this model might be implemented into practice.[Methods] GPs and other HCPs working in primary care, addiction treatment services and NGOs were invited to eight 1 day symposia (HCV Masterclass series), examining the burden and management of HCV in key populations. Peer-support sessions were also conducted, to give people affected by HCV and community-based organizations working with those directly affected, an update on the latest developments in HCV treatment.[Results] One hundred percent of participants ‘strongly agreed’ or ‘agreed’ that the Masterclass helped them to appreciate the role of integrated services in ‘the management of patients with HCV’. One hundred percent of participants indicated the importance of a ‘designated nurse to liaise with hospital services’. An improvement of knowledge regarding HCV management of patients with high-risk behaviour was registered at the end of the course.[Conclusions] Integrated approaches to healthcare and improving the knowledge of HCPs and patients of the latest developments in HCV treatment are very important strategies that can enhance the HCV care pathway and treatment outcomes.This work was supported by the European Commission through its EU Third Health Programme (Grant Agreement Number 709844) and Ireland’s Health Services Executive.Peer reviewe

Integrating hepatitis C care for at-risk groups (HepLink):baseline data from a multicentre feasibility study in primary and community care

OBJECTIVES To examine HCV prevalence and management among people who inject drugs (PWID) attending primary care and community-based health services at four European sites using baseline data from a multicentre feasibility study of a complex intervention (HepLink). METHODS Primary care and community-based health services in Dublin, London, Bucharest and Seville were recruited from the professional networks of the HepLink consortium. Patients were eligible to participate if aged ≥18 years, on opioid substitution treatment or at risk of HCV (i.e. injecting drug use, homeless or incarcerated), and attended the service. Data on patient demographics and prior HCV management were collected on participants at baseline. RESULTS Twenty-nine primary care and community-based health services and 530 patients were recruited. Baseline data were collected on all participants. Participants' mean age ranged from 35 (Bucharest) to 51 years (London), with 71%-89% male. Prior lifetime HCV antibody testing ranged from 65% (Bucharest) to 95% (Dublin) and HCV antibody positivity among those who had been tested ranged from 78% (Dublin) to 95% (Bucharest). Prior lifetime HCV RNA testing among HCV antibody-positive participants ranged from 17% (Bucharest) to 84% (London). Among HCV antibody- or RNA-positive participants, prior lifetime attendance at a hepatology/infectious disease service ranged from 6% (London) to 50% (Dublin) and prior lifetime HCV treatment initiation from 3% (London) to 33% (Seville). CONCLUSIONS Baseline assessment of the HCV cascade of care among PWID attending primary care and community-based health services at four European sites identified key aspects of the care cascade at each site that need to be improved

A CHALLENGING NEUROLOGICAL COMPLICATION IN A YOUNG HIV-INFECTED WOMAN

Background: The management of HIV infected patients with immune reconstitution inflammatory syndrome (IRIS) represents a challenge, especially in those with cerebral opportunistic infections. Case description: We present a 26 year-old woman, diagnosed with HIV infection and admitted in our hospital with severe anemia, depression and anxiety. Lab screens showed severe anemia and immunosuppression (CD4 cell count 63 cells/mm3 ) and high plasma HIV-RNA (6.25 log10 copies/mL). After one month treatment with lamivudine 3TC, tenofovir (TDF) and raltegravir RAL and important immune recovery (CD4 192 cells/mm3 ) and significant decay in HIV viral load to 1.5 log10 copies/mL were noticed. The initial clinical evolution was unfavorable with the appearance of generalized seizures, movement disturbances, auditory hallucinations and right hemiparesis. CSF exam was normal with negative bacterial and fungal cultures but with detectable HIV-RNA – 82 copies/mL (1.90 log10 copies/mL). Brain MRI showed hyperintense lesions on T2 and FLAIR sequences and hypointense on T1 sequences, localized in fronto-temporal areas, right cerebellum and pons. In evolution, there was a continuing worsening of psychiatric and neurological symptoms with severe tremor, axial hypotonia, generalized weakness and severe sleep disturbances. Atypical brain MRI lesions in the presence of severe psychiatric symptoms raised difficulties in establishing the cause of the neurological complication. The important progression of the lesion in the white matter, the appearance of contrast enhancement and the presence of JC – DNA in CSF suggested the diagnosis of PML IRIS. The patient was treated with high doses of cortisone, antipsychotic drugs and continued cART, with a slow clinical recovery and brain MRI improvement starting with 4 months of treatment. Conclusion: The diagnosis of the neurological complication was difficult due to the atypical onset, the presence of concomitant psychiatric symptoms and the atypical initial brain imaging

COMPLICAŢIE NEUROLOGICĂ SEVERĂ LA O TÂNĂRĂ CU INFECŢIE HIV

Introducere: Managementul pacienţilor cu infecţie HIV şi sindrom inflamator de reconstituţie imună (IRIS) reprezintă încă o provocare, în special la pacienţii cu infecţii oportuniste cerebrale. Prezentare de caz: Prezentăm cazul unei tinere în vârstă de 26 de ani, diagnosticată cu infecţie HIV într-un serviciu de hematologie şi internată în clinică noastră cu anemie severă, anxietate şi depresie. Probele biologice la internare au evidenţiat o anemie importantă, imunodepresie severă (CD4+ 63/mm3 ) şi o viremie HIV crescută (6,25 log10 copii/mL). După o lună de la iniţierea terapiei antiretrovirale cu schemă lamivudina 3TC, tenofovir (TDF) şi raltegravir (RAL), s-a observat o creştere importantă a imunităţii celulare (limfocite CD4+ 192/mm3 ) şi o scădere semnificativă a încărcăturii virale HIV la 1.5 log10 copii/mL. Evoluţia clinică a fost dificilă, pacienta prezentând multiple episoade de convulsii tonico-clonice generalizate, halucinaţii auditive şi instalând hemipareză dreaptă. Examenul LCR a evidenţiat 2 celule/mmc, proteinorahie normală (0,42 g/l), ARN- HIV de 82 copii/mL iar culturile bacteriene şi fungice nu au fost crescute. Examenul IRM cerebral a evidenţiat leziuni hiperintense în secvenţele T2 şi FLAIR, hipointense în T1, localizate în ariile fronto-temporale, în emisferul cerebelos drept şi în punte. Deşi PCR ADN-JC a fost pozitiv în LCR, sugerând diagnosticul de leucoencefalopatie multifocală progresivă (PML), aspectul neuro-imagistic atipic şi simptomatologia psihiatrică asociată au făcut iniţial dificilă stabilirea diagnosticului. Starea generală s-a agravat treptat în special prin accentuarea simptomatologiei psihiatrice şi neurologice (tremor sever, hipotonie axială, slăbiciune musculară generalizată, insomnie şi anxietate marcată). Progresia semnificativă a leziunilor în substanţa albă subcorticală cu priză de contrast, în contextul ameliorării statusului imunologic, a scăderii importante a viremiei HIV şi a prezenţei ADN-JC în LCR, au orientat diagnosticul spre IRIS-PML. Pacienta a primit corticoterapie în doze mari, tratament antipsihotic şi a continuat terapia antiretrovirală, cu evoluţie clinică treptat favorabilă, cu ameliorarea treptată a simptomatologiei neuropsihice. Concluzii: Diagnosticul afecţiunii neurologice a fost dificil în special din cauza debutului atipic, a prezenţei concomitente a simptomelor psihice şi a aspectului neuro-imagistic necaracteristic

PARTICULARITĂŢI ÎN INFECŢIILE BACTERIENE SEVERE LA PACIENŢII CU INFECŢIE HIV, UTILIZATORI DE DROGURI INJECTABILE

Consumul de droguri injectabile a devenit în ultima perioadă o problemă majoră de sănătate publică atăt la nivel global, cât şi în România. Incidenţa infecţiei HIV şi a hepatitelor virale la utilizatorii de droguri injectabile a înregistrat în ţara noastră o creștere alarmantă, mai ales în contextul apariţiei unor noi substanţe (denumite etnobotanice) cu efect înalt adictiv, care asociază comportamente nesterile de injectare şi efecte nocive încă insuficient cunoscute. Pe fondul imunodepresiei secundare infecţiei HIV la acești pacienţi pot să apară complicaţii infecţioase severe, cu evoluţie clinică nefavorabilă şi risc crescut de deces. În acest articol vom prezenta principalele infecţii bacteriene care sunt mai frecvent diagnosticate la utilizatorii de droguri injectabile. Endocarditele bacteriene la IDU sunt produse cel mai frecvent prin infecţia valvelor tricuspide cu Staphylococcus aureus. Alte infecţii descrise mai frecvent la aceşti pacienţi sunt cele cu localizare la nivel cutanat/ţesuturi moi, infecţii ale tractului respirator (pe fondul alterării mecanismelor locale de apărare) şi infecţii cu transmitere sexuală, în contextul unui comportament sexual la risc, influenţat frecvent de consumul de droguri recreaţionale, practică cunoscută sub numele de „ChemSEX“, mai ales în rândul bărbaţilor care au raporturi sexuale cu persoane de același sex. La acești pacienţi, utilizatori de droguri injectabile, au fost descrise și cazuri de botulism și tetanos, cu poartă de intrare la nivelul plăgii de injectare şi chiar epidemii de antrax. Pacienţii seropozitivi HIV care utilizează droguri injectabile necesită îngrijiri complexe, deseori multidisciplinare și, uneori, intervenţie chirurgicală

LISTERIA MONOCYTOGENES OUTBREAK IN EUROPE – UPDATES IN 2018

Listeria monocytogenes is the pathogen responsible for one of the most common zoonosis spread through contaminated food. It is characterized by a high capacity to withstand poor environmental conditions and to form biofilm. In general population it is most often a food-born infection, but it affects especially pregnant women, newborns, elderly and immunosuppressed persons, causing meningoencephalitis in these patients, and rarely, cardiac or osteoarticular conditions etc. Over time, both sporadic and outbreaks with broad geographic distribution have been described in Africa, Europe, or in the United States of America. Over the last 3 years, Europe has faced an increased number of cases of listeriosis, spread due to frozen vegetables (especially corn). Using molecular tests, serotype IVb with the ST6 multilocular sequence was identified as prevalent during this outbreak. The contamination source is a Hungarian company that packed and sold frozen vegetables on the market. The infectious strain persisted despite cleansing and disinfection measures. It was subsequently spread to other European Union (EU) countries. Even if the frozen vegetables were largely distributed in Europe (including Romania), and the strain was isolated in more countries, human listerios linked to these strains were registered only in 5 states. Considerable efforts are being made in order to try to stop the spread of this outbreak by improving the hygiene, disinfection and control measures, and by withdrawing potentially contaminated products from the market

CHALLENGES AND PARTICULARITIES IN THE MANAGEMENT OF SEVERE BACTERIAL INFECTIONS IN HIV-INFECTED INJECTING DRUG USERS

Injecting drug use became during last decade a major health public issue, both in Romania and around the world. Incidence of HIV and viral hepatitis in injecting drug users (IDUs) has dramatically increased due to the appearance of new highly addictive drugs (called “ethnobotanicals”) with unknown effects and associated with increased use of unsterile injecting equipment. Severe bacterial infections with poor outcome often complicate the clinical evolution of these patients, especially in case of severe immunosuppression secondary to HIV. We will describe in this review the most common bacterial infections developed due to injecting drug use. Bacterial endocarditis in IDUs are usually right-sided, Staphylococcus aureus being the most common pathogen. These patients also develop skin/soft tissues and respiratory tract infections (due to altered local defense mechanisms), as well as sexually transmitted diseases due to high risk sexual behavior, usually determined by recreational drug use. This behavior is known as “ChemSEX” and is usually practiced by men having sex with men. There were also reported cases of wound botulism, tetanus and even anthrax epidemics among IDUs. HIV infected IDUs usually require complex management with multidisciplinary approach and sometimes surgical treatment

Hepatitis B Virus Genotypes and Antiviral Resistance Mutations in Romanian HIV-HBV Co-Infected Patients

Background and Objectives: Romania has one of the highest prevalence of hepatitis B virus (HBV) infection in human immunodeficiency virus (HIV) patients, mostly in those parenterally infected during childhood; nevertheless, there are scarce data on the virological profile of co-infection. The objective of this study was to assess the prevalence of HBV genotypes and antiviral resistance-associated mutations (RAMs) in these co-infected patients, in order to monitor the viral factors associated with the evolution of liver disease. Materials and Methods: HBV genotypes and RAMs were detected using nested PCR and line probe assays (INNO-LiPA HBV genotyping assay, and INNO-LiPA HBV DR v2, Innogenetics). Results: Out of 117 co-infected patients, 73.5% had detectable HBV-DNA, but only 38.5% presented an HBV viral load >1000 IU/mL. HBV genotype A was present in 66.7% of the cases and was dominant in patients parenterally infected during early childhood, who experienced multiple treatment regimens, with a mean therapy length of 15.25 years, and present numerous mutations associated with lamivudine (LAM) resistance, but very rarely active liver disease. HBV genotype D was detected in 33.3% of the cases, mostly in recently diagnosed injecting drug users who are treatment naïve, but, nevertheless, present RAMs in 63.5% of the cases, suggesting transmitted drug resistance, and display more frequently advanced liver fibrosis (36.1% vs. 12.3%; p = 0.033). The most frequently encountered RAMs are M204V/I: 48.8%, L180M: 33.3%, L80V: 28.8%, and V173L: 42.2%. There are no significant differences in the distribution of RAMs in patients infected with different HBV genotypes, except for the L80V and N236T mutations, which were more frequently found in HBV genotype A infections (p = 0.032 and p = 0.004, respectively). Conclusions: HBV genotypes A and D are the only genotypes present in HIV–HBV co-infected patients from Romania, with different distributions according to the infection route, and are frequently associated with multiple RAMs, conferring extensive resistance to LAM

HIV INFECTION AMONG ETHNOBOTANICALS IV DRUG USERS FOLLOWED IN „DR. VICTOR BABES” CLINICAL HOSPITAL FOR INFECTIONS AND TROPICAL DISEASES

HIV/HCV co-infection is permanently increasing in our country especially among intravenous drug users (IDUs) from low socio-economical risk categories. HIV/HCV co-infection among IDUs is associated with a complex pathology, including psychiatric disorders due to severe addiction syndrome, bacterial infection at the injection site and systemic bacterial infections of various degrees of severity. Due to HIV related immunosuppression, pulmonary or extra-pulmonary tuberculosis is frequently diagnosed, with major risk for dissemination Mycobacterium tuberculosis in the general population, including MDR or XDR TB strains