Cristiana Oprea

Ongoing outbreak of multiple blood-borne infections in injecting drug users in Romania.

In the recently published 2012 annual report on the state of the drugs problem in Europe, the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) underlined the continuous increase in the drug-related infectious diseases, with a special mention for human immunodeficiency virus (HIV) infection and hepatitis C virus (HCV). According to the last data released from the EMCDDA, Romania has experienced an increase in the lifetime use for all types of illicit drugs among subjects aged 15e64 years old, from 1.7% in 2007 to 4.3% in 2010. Central estimates for the capital city, Bucharest, show an increase with 5.37% in the number of problem drug users, in the 18e49-year old age group only: from 17 387 in 2008 to 18 316 in 2010, with a low number of treatment demands (between 10 and 15%); at the country level, these data are largely unknown. There are few published data on the prevalence of drug-related infectious diseases. Surveys using respondent-driven sampling or testing among those looking for medical assistance (both consisting on rather small samples of 200e500 drug users) reported high, although slightly decreasing levels, of HCV infection (from 72.6% in 2008 to 68.5% in 2011, with higher levels among those >34 years old); increasing rates of hepatitis B virus (HBV)

Cerebral toxoplasmosis in children and adolescents from “Dr. Victor Babeş” Hospital pediatric HIV-cohort

Cerebral toxoplasmosis (Toxo) is rarely described in children. The Romanian pediatric cohort consists of children that have been infected parenterally in the late ’80s. We aimed to describe the prevalence, clinical findings and outcome of Toxo in children and adolescents from the Romanian Pediatric Cohort, that have been diagnosed in the “Dr. Victor Babes” Hospital, one of the main reference centers for HIV from Romania n nCerebral toxoplasmosis was diagnosed based on CDC case definition (presumptive and definitive diagnosis). We reviewed retrospectively the charts of all 29 children diagnosed with Toxo starting 1996, recording the demographic, HIV markers, antiretroviral treatment, clinical and neuroimaging data, treatment and outcome of Toxo. n nThe prevalence of Toxo was 4.8% from 604 patients followed in the Hospital. Out of 29 patients diagnosed with Toxo, 19 were girls and 28 had parenterally and 1 had vertically acquired HIV. The mean age at HIV diagnosis was 11.5±6.5 years, and 15.6±5.3 years at Toxo diagnosis. In 10 patients HIV was diagnosed concomitantly with Toxo. At onset 89.7% patients had focal neurological signs and 62.1% had headache. Median CD4 count was 60 (95% CI for median 27-95) lf/cmm. 28 patients had positive T. gondii IgG antibodies in plasma and/or cerebrospinal fluid. Only 6 patients had treatment with cotrimoxazole, most of them being treated with pyrimethamine/sulphadoxine combination and alternatively with atovaquone. 69% of patients had any adverse reactions to Toxo treatment. Most adverse reactions were cutaneous in 10 patients (5 severe) and anemia in 7 patients. Nine patients had antiretroviral therapy (ART) before Toxo diagnosis, out of them 1 had mono, 1 dual therapy, 6 were failing cART and one patient had immune reconstitution syndrome. Ten patients (34.5%) died. The median survival time was 117 months. In univariate analysis survival was correlated with shorter time from onset to admission (p=0.04) while on multivariate analysis diagnosis in the post-cART period was the only factor associated with longer survival (p=0.03). 14 of 19 patients recovered with sequels, most of them motor deficits. n nCerebral toxoplasmosis in this particular pediatric cohort shared common features with that reported in adults pertaining to prevalence in pre-cART period and pathogenic mechanism. Survival was associated with a more rapid diagnosis of cerebral toxoplasmosis and with access to cART.

Impact of hepatitis C virus core mutations on the response to interferon-based treatment in chronic hepatitis C

AIM To determine whether hepatitis C virus (HCV) core substitutions play a role in the response to interferon-based treatment in Caucasian patients. METHODS One hundred eight HCV chronically infected patients initiating treatment with pegylated IFN plus ribavirin for 48 wk were tested for baseline substitutions at codons 70 and 91 of the viral core protein (BigDye Terminator vers.3.1, Applied Biosystems,) and for genetic polymorphisms in host IL28B gene rs12979860 (Custom TaqMan 5 allelic discrimination assay; Applied Biosystems). RESULTS Of the patients, all were infected with HCV genotype 1b, 44.4% had low baseline HCV viral load, and 37.9% had mild/moderate fibrosis. Only 38.9% achieved therapeutic success, defined as sustained virological response (SVR). Eighty-eight percent of the patients presented at least one substitution at core position 70 (R70Q/H) or/and position 91 (L91M). The favorable IL28B CC polymorphism was detected in only 17.6% of the patients. In the univariate analysis, young age (P < 0.001), urban residence (P = 0.004), IL28B CC genotype (P < 0.001), absence of core mutations (P = 0.005), achievement of rapid virologic response (P < 0.001) and early virological response (P < 0.001) were significantly correlated with SVR. A multivariate analysis revealed three independent predictors of therapeutic success: young age (P < 0.001), absence of core substitutions (P = 0.04) and IL28B CC genotype (P < 0.001); the model correctly classified 75.9% of SVR cases with a positive predictive value of 80.7%. CONCLUSION HCV core mutations can help distinguish between patients who can still benefit from the affordable IFN-based therapy from those who must be treated with DAAs to prevent the evolution towards end-stage liver disease.

HCV non-1b genotypes in injecting drug users from Romania

INTRODUCTIONnChronic hepatitis C cases diagnosed in Romania were mostly related to unsafe parenteral treatments and blood transfusions; HCV genotype 1b was prevalent. During the last decade, an increasing number of HCV infections was reported among people who inject drugs (PWID). The aim of the current study was to test if this epidemiological shift triggered a diversification of the circulating viral strains.nnnMETHODOLOGYnHCV genotypes were determined by reverse hybridization in 130 HCV-infected PWID (87.7% males; mean age 27.9 ± 6.7 years, injecting drugs for 8.1 ± 4.8 years).nnnRESULTSnHIV-HCV co-infection was diagnosed in 80.8% of the subjects and 26.9% were HIV-HCV-HBV triple infected. Active HCV viral replication was present in 104 PWID (80%), more frequently in those HIV-co-infected (91.4% vs. 52% in HCV mono-infected, and 77.148.5% in HIV-HCV-HBV triple-infected, p = 0.0001). Non-1b genotypes were prevalent (54.8%), with subtype 1a the most commonly detected (24%), followed by genotypes 3a (14.4%) and 4 (7.7%). Mixed infections with genotypes 1a and 1b were found in nine subjects (8.7%). There was no difference in the genotypes frequencies based on HIV or HBV co-infection status, length of drug usage, or associated risk factors (tattoos, piercing, detention).nnnCONCLUSIONnThe continuous surveillance of HCV genotypes in PWID from Romania will add valuable information to the overall European epidemiological picture, with important therapeutic implications.

Alarming increase in tuberculosis and hepatitis C virus (HCV) among HIV infected intravenous drug users

In the last years, we observed an alarming increase in the number of newly diagnosed HIV infected intravenous drug users (IDUs) co‐infected with hepatitis viruses or with severe bacterial infections. The aim of our study was to assess the incidence, the demographic and clinical characteristics of IDUs diagnosed with HIV, HCV and tuberculosis (TB).

Screening for osteo-renal involvement in the Romanian HIV cohort

Background When assessing comorbidities in HIV-infected patients, the bone and the kidney represent important target organs that can potentially be affected by both virus and antivirals. Given the particular characteristics of the Romanian HIV cohort [1], most of the patients have experienced HIV infection in childhood and have received multiple therapeutic regimens since the advent of antiretroviral (ARV) therapy. Thus, the need to screen for osteo-renal impairment in these patients is high on the priority list [2].

HIV care in Central and Eastern Europe: How close are we to the target?

OBJECTIVESnThe aim of this survey was to describe the current status of HIV care in the countries of Central and Eastern Europe and to investigate how close the region is to achieving the UNAIDS 2020 target of 90-90-90.nnnMETHODSnIn 2014, data were collected from 24 Central and Eastern European countries using a 38-item questionnaire.nnnRESULTSnAll countries reported mandatory screening of blood and organ donors for HIV. Other groups subjected to targeted screening included people who inject drugs (PWID) (15/24, 62.5%), men who have sex with men (MSM) (14/24, 58.3%), and sex workers (12/24, 50.0%). Only 14 of the 24 countries (58.3%) screened pregnant women. The percentages of late presentation and advanced disease were 40.3% (range 14-80%) and 25.4% (range 9-50%), respectively. There was no difference between countries categorized by income or by region in terms of the percentages of persons presenting late or with advanced disease. The availability of newer antiretroviral drugs (rilpivirine, etravirine, darunavir, maraviroc, raltegravir, dolutegravir) tended to be significantly better with a higher country income status. Ten countries reported initiating antiretroviral therapy (ART) regardless of CD4+ T cell count (41.7%), five countries (20.8%) used the threshold of <500 cells/μl, and nine countries (37.5%) used the threshold of <350cells/μl. Initiation of ART regardless of the CD4+ T cell count was significantly more common among high-income countries than among upper-middle-income and lower-middle-income countries (100% vs. 27.3% and 0%, respectively; p=0.001). Drugs were provided free of charge in all countries and mostly provided by governments. There were significant discrepancies between countries regarding the follow-up of people living with HIV.nnnCONCLUSIONSnThere are major disparities in the provision of HIV care among sub-regions in Europe, which should be addressed. More attention in terms of funding, knowledge and experience sharing, and capacity building is required for the resource-limited settings of Central and Eastern Europe. The exact needs should be defined and services scaled up in order to achieve a standard level of care and provide an adequate and sustainable response to the HIV epidemic in this region.

Increasing Incidence of HIV-associated tuberculosis in Romanian injecting drug users

A high prevalence of tuberculosis (TB) among HIV‐positive injecting drug users (IDUs) may fuel the TB epidemic in the general population of Romania. We determined the frequency and characteristics of TB in HIV‐infected IDUs referred to a national centre.

Hepcare Europe - bridging the gap in the treatment of hepatitis C: study protocol

ABSTRACT Background: Hepatitis C (HCV) infection is highly prevalent among people who inject drugs (PWID). Many PWID are unaware of their infection and few have received HCV treatment. Recent developments in treatment offer cure rates >90%. However, the potential of these treatments will only be realised if HCV identification among PWID with linkage to treatment is optimised. This paper describes the Hepcare Europe project, a collaboration between five institutions across four member states (Ireland, UK, Spain, Romania), to develop, implement and evaluate interventions to improve the identification, evaluation and treatment of HCV among PWID. Methods: A service innovation project and a mixed-methods, pre-post intervention study, Hepcare will design and deliver interventions in Dublin, London, Seville and Bucharest to enhance PWID engagement and retention in the cascade of HCV care. Results: The feasibility, acceptability, potential efficacy and cost-effectiveness of these interventions to improve care processes and outcomes among PWID will be evaluated. Conclusion: Hepcare has the potential to make an important impact on patient care for marginalised populations who might otherwise go undiagnosed and untreated. Lessons learned from the study can be incorporated into national and European guidelines and strategies for HCV.

Extrapulmonary tuberculosis in HIV infected patients from the cohort of “Dr Victor Babeş” Hospital, Bucharest, Romania

The infection with Mycobacterium tuberculosis remains the most frequent opportunistic infection in HIV seropositive patients. In Romania the incidence of tuberculosis (TB) in general population is the highest in Europe with 70.9 per 10,000 inhabitants. n nWe investigated the incidence of extrapulmonary tuberculosis in “Dr Victor Babes” Hospital cohort and its epidemiological, clinical and outcome particularities. n nWe performed an observational retrospective study during 2003-2013 among the HIV infected patients from our cohort. We selected the patients with extrapulmonary tuberculosis. The data was obtained from the medical charts and outpatient records. n nFrom 280 cases of confirmed infection we found 55 cases of extrapulmonary tuberculosis. The HIV transmission route was parenteral in 72.55% (95%CI 58.75 to 87.40) of cases. The median age at TB diagnosis was 24 years (95%, CI 20.16 to 25.03) with male/female ratio of 1,21. At the time of TB diagnosis the median CD4 count was 87 cells/cmm (95% CI 72.87 to 131.31). The percent of patients with concomitant pulmonary and extrapulmonary localization was 57.7% (95% CI 40.79 to 72.78). The number of patients with recurrent TB was 17 and 5 had more than one extrapulmonary TB in the studied period. The most frequent extrapulmonary involvement was ganglionar 35/51 (69.7% 95% CI 54.91 to 79.74). The commonest manifestations were fever (57.5% 95% CI 40.79 to 72.78), weight loss (30% 95% CI 17.25 to 47.46) and adenopathy (24.2% 95% CI 12.60 to 41.25) and the median time from the onset to diagnosis was 4 weeks (95% CI 2.611 to 5.209). In 54.5% (95% CI 40.79 to 72.78) of cases the smear was positive, cultures were positive in 69.7% (95% CI 55.61 to 85.10) and in 30% (95% CI 17.25 to 47.46) of cases the diagnosis was made on histopathologic examination. In 45.5% (95% CI 32.50 to 64.78) we obtained an antibiogram that confirmed MDR TB in 11.5% (95% CI 2.37 to 24.34). All patients received treatment and 7.84% (95% CI 6.17 to 31.40) abandoned treatment and 11.76% (95% CI 2.37 to 23.4) died. n nAlthough the extrapulmonary involvement is not very frequent, the diagnosis can be challenging and can take a lot of time especially when it is difficult to obtain a specimen. In a febrile immunodepressed patient extrapulmonary TB should be always considered.