Simona Ruta | University of Medicine and Pharmacy "Carol Davila" Bucharest (original) (raw)
Papers by Simona Ruta
Roumanian archives of microbiology and immunology, 2018
Biomedicines
HIV-HBV coinfected patients have higher rates of liver-related morbidity, hospitalizations, and m... more HIV-HBV coinfected patients have higher rates of liver-related morbidity, hospitalizations, and mortality compared to HBV or HIV mono-infected ones. Clinical studies have shown an accelerated progression of liver fibrosis and an increased incidence of HCC, resulting from the combined action of HBV replication, immune-mediated hepatocytolysis, and HIV-induced immunosuppression and immunosenescence. Antiviral therapy based on dually active antiretrovirals is highly efficient, but late initiation, global disparities in accessibility, suboptimal regimens, and adherence issues may limit its impact on the development of end-stage liver disease. In this paper, we review the mechanisms of liver injuries in HIV-HBV coinfected patients and the novel biomarkers that can be used for treatment monitoring in HIV-HBV coinfected persons: markers that assess viral suppression, markers for liver fibrosis evaluation, and predictors of oncogenesis.
Infectious Diseases
In the genomic medicine era, the emergence of SARS-CoV-2 was immediately followed by viral genome... more In the genomic medicine era, the emergence of SARS-CoV-2 was immediately followed by viral genome sequencing and world-wide sequences sharing. Almost in real-time, based on these sequences, resources were developed and applied around the world, such as molecular diagnostic tests, informed public health decisions, and vaccines. Molecular SARS-CoV-2 variant surveillance was a normal approach in this context yet, considering that the viral genome modification occurs commonly in viral replication process, the challenge is to identify the modifications that significantly affect virulence, transmissibility, reduced effectiveness of vaccines and therapeutics or failure of diagnostic tests. However, assessing the importance of the emergence of new mutations and linking them to epidemiological trend, is still a laborious process and faster phenotypic evaluation approaches, in conjunction with genomic data, are required in order to release timely and efficient control measures.
Biomedicines
The continuous variability of SARS-CoV-2 and the rapid waning of specific antibodies threatens th... more The continuous variability of SARS-CoV-2 and the rapid waning of specific antibodies threatens the efficacy of COVID-19 vaccines. We aimed to evaluate antibody kinetics one year after SARS-CoV-2 vaccination with an mRNA vaccine in healthcare workers (HCW), with or without a booster. A marked decline in anti-Spike(S)/Receptor Binding Domain (RBD) antibody levels was registered during the first eight months post-vaccination, followed by a transitory increase after the booster. At three months post-booster an increased antibody level was maintained only in HCW vaccinated after a prior infection, who also developed a higher and long-lasting level of anti-S IgA antibodies. Still, IgG anti-nucleocapsid (NCP) fades five months post-SARS-CoV-2 infection. Despite the decline in antibodies one-year post-vaccination, 68.2% of HCW preserved the neutralization capacity against the ancestral variant, with a decrease of only 17.08% in the neutralizing capacity against the Omicron variant. Neverthe...
Medicina
Background and Objectives: Romania has one of the highest prevalence of hepatitis B virus (HBV) i... more 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 r...
The predictive value of two easy-to-determine serum biomarkers: IP-10 (Interferon-gamma inducible... more The predictive value of two easy-to-determine serum biomarkers: IP-10 (Interferon-gamma inducible protein-10 kD) and sCD26 (soluble CD26) on the virological response of interferon-based therapy was assessed in 119 patients with chronic hepatitis C. Patients who obtained sustained virological response (SVR) had significantly decreased baseline IP-10 concentrations as compared to non-responders (mean IP-10 = 338 ± 200 pg/mL vs. 472.7 ± 254 g/mL; p=0.003). Correlation of this inexpensive serological marker with IL2B genotype and baseline HCV viral load can be used in the selection of patients who might benefit from interferon-based therapies, which are currently available in developing economies. On the contrary, there was no correlation between the baseline concentration of sCD26 and the outcome of treatment. IP-10 might be a suitable biomarker to predict virological success after pegylated interferon alpha and ribavirin treatment.
Romanian Biotechnological Letters, 2020
Balkan Medical Journal, 2018
Journal of NeuroVirology, 2019
Objectives: HIV-associated neurocognitive disorder (HAND) is characterized by chronic immune acti... more Objectives: HIV-associated neurocognitive disorder (HAND) is characterized by chronic immune activation. We aimed to identify biomarkers associated with HAND and to investigate their association with cognitive function and sex, in a homogenous cohort of HIV infected (HIV+) young adults, parenterally infected during early childhood. Methods: 144 HIV+ Romanian participants (51% women) without major confounders underwent standardized neurocognitive and medical evaluation in a cross-sectional study. IFN-γ, IL-1β, IL-6, CCL2, CXCL8, CXCL10, and TNF-α were measured in plasma in all participants and in cerebrospinal fluid (CSF) in a subgroup of 56 study participants. Biomarkers were compared to neurocognitive outcomes, and the influence of sex and HIV disease biomarkers were assessed. Results: In this cohort of young adults (median age of 24 years), the rate of neurocognitive impairment (NCI) was 36.1%. Median current CD4+ count was 479 cells/mm 3 and 36.8% had detectable plasma viral load. Women had better HIV-associated overall status. In plasma,
Hepatitis Monthly, 2019
Objectives: The study aimed to investigate the role of miR-125b as a non-invasive biomarker in ch... more Objectives: The study aimed to investigate the role of miR-125b as a non-invasive biomarker in chronic hepatitis C. Methods: An observational study was conducted on 94 treatment-naïve HCV-infected patients (mean age 49.8 ± 11.5 years, 59.6% females). Liver fibrosis was assessed by transient elastography (TE) and the expression of miR-125b in plasma was quantified by real-time PCR. Results: All patients were infected with HCV genotype 1b and had active viral replication, 42.6% had significant cytolysis, and 73.4% had increased serum gamma-glutamyl transferase (GGT) values. Significant fibrosis (liver stiffness measured by TE of > 7.1 kPa) was present in 61.7% of the patients. No significant associations were found between miR-125b expression and baseline HCV viral load (P = 0.56), IL28B polymorphisms (P = 0.5), alpha-fetoprotein levels (P = 0.27), and patients' gender (P = 0.13) or age (P = 0.5). In a univariate analysis, the miR-125b expression level was significantly correlated with ALT (P = 0.001) and GGT levels (P < 0.0001). An up-regulated expression of miR-125b was found in plasma samples from patients with advanced liver fibrosis as compared to those with mild/moderate fibrosis [mean miR-125b value = 0.002 versus 0.001 (P = 0.02)]. In a multiple regression analysis, an upregulated miR-125b expression level remained independently in association only with significant fibrosis and increased GGT level (P = 0.026; R 2 = 0.242). Conclusions: An up-regulated miR-125b expression might be an indicator of severe liver fibrosis in patients with chronic hepatitis C, independent of the viral replication level.
AIDS (London, England), Jan 14, 2018
Sex differences in cognition of HIV positive (HIV) patients are controversial. We aimed to invest... more Sex differences in cognition of HIV positive (HIV) patients are controversial. We aimed to investigate the relationship between cognition, HIV status, and sex, in a highly homogenous cohort of young Romanians parenterally infected during early childhood. In total, 250 HIV participants were compared with age-matched HIV negative (HIV) controls (n = 72) in a cross-sectional study. After standardized neurocognitive, psychological testing and medical evaluation, linear regression was used to assess the effect of sex and HIV on neurocognitive outcomes. Study participants were on average 23 years old with balanced sex distribution (% women = 52% vs. 43%). HIV were more educated (12.7 vs. 11.6 years, P = 0.002).HIV status was associated with a lower global performance (β = -0.22, P < 0.001), after controlling for age and education. HIV women had better previous and current HIV-associated markers. The effect of HIV on global cognition did not differ between sexes in most cognitive domain...
Journal of Neuroimmunology, 2016
We evaluated the impact of latent toxoplasmosis (LT) on neurocognitive (NC) and neurobehavioural ... more We evaluated the impact of latent toxoplasmosis (LT) on neurocognitive (NC) and neurobehavioural functioning in young adults with and without chronic HIV infection, using a standardised NC test battery, self-reported Beck Depression Inventory, Frontal System Behaviour Scale, MINI-International Neuropsychiatric Interview and risk-assessment battery. 194 young adults (median age 24 years, 48.2% males) with chronic HIV infection (HIV+) since childhood and 51 HIV seronegative (HIV-) participants were included. HIV+ individuals had good current immunological status (median CD4: 479 cells/μL) despite a low CD4 nadir (median: 93 cells/μL). LT (positive anti-Toxoplasma IgG antibodies) was present in one third of participants. The impairment rates in the HIV-with and without Toxo were not significantly different (p=0.17). However, we observed an increasing trend (p<0.001) in impairment rates with HIV and LT status: HIV-/LT-(6.1%); HIV-/LT+ (22%), HIV+/LT-(31%), HIV+/LT+ (49%). In a multivariable analysis using the entire study group there were main effects on cognition for HIV and also for LT. Within the HIV+ group LT was associated with worse performance globally (p=0.006), in memory (p=0.009), speed of information processing (p=0.01), verbal (p=0.02) and learning (p=0.02) domains. LT was not associated with depressive symptoms, frontal systems dysfunction or risk behaviors in any of the groups. HIV participants with lower Toxoplasma antibody concentration had worse NC performance, with higher GDS values (p=0.03) and worse learning (p=0.002), memory (p=0.006), speed of information processing (p=0.01) T scores. Latent Toxoplasmosis may contribute to NC impairment in young adults, including those with and without chronic HIV infection.
Current Organic Chemistry, 2016
Hemoglobinopathies, such as β-thalassemia and sickle cell disease (SCD), are among the most commo... more Hemoglobinopathies, such as β-thalassemia and sickle cell disease (SCD), are among the most common congenital diseases in the world, with high mortality and morbidity rates. The most straightforward approach to correct the main culprit in hemoglobinopathies-the imbalance between the amounts of alpha-like globins/beta-like globins-will need to target directly the gene structure or their regulatory elements in order to obtain a sustained therapeutic effect. Finding effective methods to deliver the genetic " blueprints " of the correct and functional protein or, even better, the " DNA repairing kit " able to do the job in situ, remains a major challenge, despite the fact that gene therapy is already used in different diseases. Members of several viral families were employed as " Trojan horses " using the virus ability to deliver a modified genetic material inside the cell and to manipulate the host replication machinery to produce the encoded proteins. Recently, non-viral vectors are gaining advantages for genome correction, especially after the exponential development of the genome editing approaches that can provide precise in situ modifications. This review summarizes the recent advances in the viral and non-viral delivery strategies and emphasizes the therapeutic potential of different approaches designed to correct the genetic defects responsible for the most common hemoglobinopathies.
GERMS, 2015
Background The Romanian HIV epidemic is characterized by a high prevalence among children born in... more Background The Romanian HIV epidemic is characterized by a high prevalence among children born in the late '80s, perinatally infected. The impact of long-term treatment on their offspring is unknown. We evaluated the influence of prenatal care on the rate of premature birth among the HIV-exposed children of heavily treated HIV-infected mothers in two Romanian centers. Methods We retrospectively analyzed data on all patients born by HIV-infected mothers between 2006 and 2012 followed up in two main regional centers. We compared the rate of premature birth and the differences between the sites regarding children and maternal demographic characteristics and antiretroviral exposure in pregnant women. Results A total of 358 children born to 315 women were enrolled between 2006-2012, 262 children from the National Institute for Infectious Diseases "Prof. Dr. Matei Balș" Bucharest (NIID) and 96 children from the Clinical Infectious Diseases Hospital Constanța (IDHC). Gender rate in newborns and mean age in mothers were similar. We recorded statistically significant differences between centers in the rate of HIV vertical transmission (16.8% vs. 6.2%, p=0.002) and prematurity (25.2 vs. 14.6%, p=0.023). The most used antiretroviral combination during pregnancy in IDHC was boosted lopinavir and fixed dose zidovudine-lamivudine (66% of cases), while in NIID a greater diversity of antiretrovirals were used. Women from IDHC were more frequently treated during pregnancy (83.3% vs. 68.6%, p=0.004). HCV coinfection and illegal drug use were associated with prematurity in the NIID cohort (p=0.037, p=0.024). Conclusion We found a higher rate of premature birth and HIV infection in NIID. In IDHC we found a higher rate of low birth weight in children and a higher rate of heavily treated women. Prematurity was associated with hepatitis C infection and illegal drug use in the NIID cohort. Keywords HIV exposure, antiretroviral drugs, prematurity Background 1 Starting with 1990 Romania faced a particular HIV epidemic, characterized by a large number of
Romanian journal of virology
Hepatitis C is and will be a major public health concern. Confirmed infections were reported from... more Hepatitis C is and will be a major public health concern. Confirmed infections were reported from all Romanian counties but important differences between regions raise several explanations. Differences may reflect the different levels of testing, the performances of laboratories in confirming initially reactive samples or the risk factors higher prevalence. We have suggested that the prevalence of anti HCV infections can be a surrogate marker for the quality of parenteral medical or paramedical interventions. Present report identified additional problems in the surveillance of HCV infection in children. We screened 1787 samples from children hosted in orphanages (children under three years old) or in preschool children institutions (between 3-7 years old). We detected 31 repeatedly reactive samples with two EIA screening kits but confirmed only 8 in WB anti HCV. Four confirmed samples come from children under four months old suggesting maternally transmitted antibodies. In highly en...
Journal of medicine and life, Jan 14, 2011
The central nervous system can act as a compartment in which HIV can replicate independently from... more The central nervous system can act as a compartment in which HIV can replicate independently from plasma, and also as a sanctuary in which, under suboptimal drug pressure, HIV antiretroviral genetic variants can occur. Continuous replication of HIV in brain can contribute to neurocognitive impairment. Therefore, reaching adequate concentrations of antiretrovirals in the central nervous system might be essential in providing neuroprotection and improving neurocognition. Antiretrovirals have a restricted entry into the brain, due to several factors: the unique structure of the blood-brain barrier, and the existence of efficient efflux mechanisms. However, there is a high variability of antiretrovirals in reaching therapeutic drug concentrations in cerebrospinal fluid, that depend on the characteristics of the antiretrovirals (molecular weight, lipophilicity, protein binding) and on their capacity to be substrate for efflux transporters. The review aims to discuss the main mechanisms t...
Romanian journal of virology
Variability is a hallmark of HIV viruses both at the genetic and the phenotypic level. Viral sequ... more Variability is a hallmark of HIV viruses both at the genetic and the phenotypic level. Viral sequencing and phylogenetic analysis of many isolates revealed specific distribution of HIV-1 subtypes according to the geographic location and route of transmission. In Romania, the currently available data coming from the study of pediatric HIV infection suggest the predominance of subtype F. However, there are few data concerning the distribution of HIV-1 subtypes among adults. We investigated the changes in the distribution of different HIV-1 subtypes among HIV-1 infected adult patients from Bucharest over a 6 years period (1992-1998) by means of V3 binding assays. The analysis of the relative incidence of different HIV-1 serotypes revealed the steady predominance of serotype F (50-75%) among the adults from Bucharest and a small but constant increase of the number of samples with serotype B- from 5% in 1994 to 14% in 1998. In contrast, the serotype E is either absent or weakly represent...
Romanian biotechnological letters, 2011
BACKGROUND AND OBJECTIVE: As available data on HIV-1 strains from Romania indicate the prevalence... more BACKGROUND AND OBJECTIVE: As available data on HIV-1 strains from Romania indicate the prevalence of a particular subtype- F, not found in other European countries, we aimed at investigating the impact on drug susceptibility of mutations associated with drug resistance and their correlation with the virological and immune response to therapy. METHODS: 38 long term survivors, HIV-1 parenterally infected in childhood, with repeated virological failures, were genotyped for drug resistance and subtype determination. A phylogenetic tree of aligned reversetranscriptase sequences was built. RESULTS: 94.7% of all the patients'strains were subtype F1, clustering together with other Romanian and Angolan F1 strains. Despite the long and complex treatments, 15.8% of patients had wild type virus, 68.4% were fully susceptible to protease inhibitors, 47.3% to non-nucleoside reverstranscriptase inhibitors, 28.9% to nucleoside reverstranscriptase inhibitors. Only 13.2% were resistant to all anti...
BMC Infectious Diseases, 2014
Hepatitis Monthly, 2013
Background: Due to a recent alarming increase in the number of HIV-HCV co-infected patients in Ro... more Background: Due to a recent alarming increase in the number of HIV-HCV co-infected patients in Romania. Objectives: A cross sectional study was conducted to assess the baseline predictors of liver disease evolution. Patients and Methods: 83 HIV-HCV co-infected patients, untreated for HCV infection, were evaluated for viral replication, liver fibrosis (estimated by a noninvasive marker-FIB4), and plasma levels of IP-10 (interferon-gamma inducible protein 10)-a cytokine associated with an unfavorable outcome of HCV infection. Results: The median value for HCV viral load was high (6.3 log10 IU/mL), 98.8% of the patients were infected with HCV genotype 1. Although 53% of the patients received antiretroviral therapy (cART), only 31.8% of these achieved undetectable HIV levels. HCV viral load was significantly higher in patients with AIDS (6.4 vs. 6.1 log10IU/mL; P = 0.04), and in those naïve for cART (6.5 vs. 5.9 log10 IU/mL; P = 0.04). Severe fibrosis was directly correlated with immunosupression (56% vs. 17.4%, P = 0.03), HCV replication (6.1 vs. 4.9 log10IU/mL P = 0.008), and IP-10 median values (312 vs. 139 pg/ml, P=0.008). A serum IP-10 level higher than 400 pg/mL was significantly associated with FIB-4 median values (4.09 vs. 1.7, P = 0.004), HCV viral load (6.4 vs. 6.1 log10 IU/mL, P = 0.02) and ALT level (206.8 vs. 112.4 IU/L, P = 0.05). Conclusions: An important part of the HIV-HCV co-infected patients had negative baseline predictors for the evolution of HCV infection; their therapeutical management must be conducted with special attention towards adherence and potential overlapping drug toxicities. High concentrations of plasma IP-10 are reliable markers for the severity of liver disease.
Roumanian archives of microbiology and immunology, 2018
Biomedicines
HIV-HBV coinfected patients have higher rates of liver-related morbidity, hospitalizations, and m... more HIV-HBV coinfected patients have higher rates of liver-related morbidity, hospitalizations, and mortality compared to HBV or HIV mono-infected ones. Clinical studies have shown an accelerated progression of liver fibrosis and an increased incidence of HCC, resulting from the combined action of HBV replication, immune-mediated hepatocytolysis, and HIV-induced immunosuppression and immunosenescence. Antiviral therapy based on dually active antiretrovirals is highly efficient, but late initiation, global disparities in accessibility, suboptimal regimens, and adherence issues may limit its impact on the development of end-stage liver disease. In this paper, we review the mechanisms of liver injuries in HIV-HBV coinfected patients and the novel biomarkers that can be used for treatment monitoring in HIV-HBV coinfected persons: markers that assess viral suppression, markers for liver fibrosis evaluation, and predictors of oncogenesis.
Infectious Diseases
In the genomic medicine era, the emergence of SARS-CoV-2 was immediately followed by viral genome... more In the genomic medicine era, the emergence of SARS-CoV-2 was immediately followed by viral genome sequencing and world-wide sequences sharing. Almost in real-time, based on these sequences, resources were developed and applied around the world, such as molecular diagnostic tests, informed public health decisions, and vaccines. Molecular SARS-CoV-2 variant surveillance was a normal approach in this context yet, considering that the viral genome modification occurs commonly in viral replication process, the challenge is to identify the modifications that significantly affect virulence, transmissibility, reduced effectiveness of vaccines and therapeutics or failure of diagnostic tests. However, assessing the importance of the emergence of new mutations and linking them to epidemiological trend, is still a laborious process and faster phenotypic evaluation approaches, in conjunction with genomic data, are required in order to release timely and efficient control measures.
Biomedicines
The continuous variability of SARS-CoV-2 and the rapid waning of specific antibodies threatens th... more The continuous variability of SARS-CoV-2 and the rapid waning of specific antibodies threatens the efficacy of COVID-19 vaccines. We aimed to evaluate antibody kinetics one year after SARS-CoV-2 vaccination with an mRNA vaccine in healthcare workers (HCW), with or without a booster. A marked decline in anti-Spike(S)/Receptor Binding Domain (RBD) antibody levels was registered during the first eight months post-vaccination, followed by a transitory increase after the booster. At three months post-booster an increased antibody level was maintained only in HCW vaccinated after a prior infection, who also developed a higher and long-lasting level of anti-S IgA antibodies. Still, IgG anti-nucleocapsid (NCP) fades five months post-SARS-CoV-2 infection. Despite the decline in antibodies one-year post-vaccination, 68.2% of HCW preserved the neutralization capacity against the ancestral variant, with a decrease of only 17.08% in the neutralizing capacity against the Omicron variant. Neverthe...
Medicina
Background and Objectives: Romania has one of the highest prevalence of hepatitis B virus (HBV) i... more 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 r...
The predictive value of two easy-to-determine serum biomarkers: IP-10 (Interferon-gamma inducible... more The predictive value of two easy-to-determine serum biomarkers: IP-10 (Interferon-gamma inducible protein-10 kD) and sCD26 (soluble CD26) on the virological response of interferon-based therapy was assessed in 119 patients with chronic hepatitis C. Patients who obtained sustained virological response (SVR) had significantly decreased baseline IP-10 concentrations as compared to non-responders (mean IP-10 = 338 ± 200 pg/mL vs. 472.7 ± 254 g/mL; p=0.003). Correlation of this inexpensive serological marker with IL2B genotype and baseline HCV viral load can be used in the selection of patients who might benefit from interferon-based therapies, which are currently available in developing economies. On the contrary, there was no correlation between the baseline concentration of sCD26 and the outcome of treatment. IP-10 might be a suitable biomarker to predict virological success after pegylated interferon alpha and ribavirin treatment.
Romanian Biotechnological Letters, 2020
Balkan Medical Journal, 2018
Journal of NeuroVirology, 2019
Objectives: HIV-associated neurocognitive disorder (HAND) is characterized by chronic immune acti... more Objectives: HIV-associated neurocognitive disorder (HAND) is characterized by chronic immune activation. We aimed to identify biomarkers associated with HAND and to investigate their association with cognitive function and sex, in a homogenous cohort of HIV infected (HIV+) young adults, parenterally infected during early childhood. Methods: 144 HIV+ Romanian participants (51% women) without major confounders underwent standardized neurocognitive and medical evaluation in a cross-sectional study. IFN-γ, IL-1β, IL-6, CCL2, CXCL8, CXCL10, and TNF-α were measured in plasma in all participants and in cerebrospinal fluid (CSF) in a subgroup of 56 study participants. Biomarkers were compared to neurocognitive outcomes, and the influence of sex and HIV disease biomarkers were assessed. Results: In this cohort of young adults (median age of 24 years), the rate of neurocognitive impairment (NCI) was 36.1%. Median current CD4+ count was 479 cells/mm 3 and 36.8% had detectable plasma viral load. Women had better HIV-associated overall status. In plasma,
Hepatitis Monthly, 2019
Objectives: The study aimed to investigate the role of miR-125b as a non-invasive biomarker in ch... more Objectives: The study aimed to investigate the role of miR-125b as a non-invasive biomarker in chronic hepatitis C. Methods: An observational study was conducted on 94 treatment-naïve HCV-infected patients (mean age 49.8 ± 11.5 years, 59.6% females). Liver fibrosis was assessed by transient elastography (TE) and the expression of miR-125b in plasma was quantified by real-time PCR. Results: All patients were infected with HCV genotype 1b and had active viral replication, 42.6% had significant cytolysis, and 73.4% had increased serum gamma-glutamyl transferase (GGT) values. Significant fibrosis (liver stiffness measured by TE of > 7.1 kPa) was present in 61.7% of the patients. No significant associations were found between miR-125b expression and baseline HCV viral load (P = 0.56), IL28B polymorphisms (P = 0.5), alpha-fetoprotein levels (P = 0.27), and patients' gender (P = 0.13) or age (P = 0.5). In a univariate analysis, the miR-125b expression level was significantly correlated with ALT (P = 0.001) and GGT levels (P < 0.0001). An up-regulated expression of miR-125b was found in plasma samples from patients with advanced liver fibrosis as compared to those with mild/moderate fibrosis [mean miR-125b value = 0.002 versus 0.001 (P = 0.02)]. In a multiple regression analysis, an upregulated miR-125b expression level remained independently in association only with significant fibrosis and increased GGT level (P = 0.026; R 2 = 0.242). Conclusions: An up-regulated miR-125b expression might be an indicator of severe liver fibrosis in patients with chronic hepatitis C, independent of the viral replication level.
AIDS (London, England), Jan 14, 2018
Sex differences in cognition of HIV positive (HIV) patients are controversial. We aimed to invest... more Sex differences in cognition of HIV positive (HIV) patients are controversial. We aimed to investigate the relationship between cognition, HIV status, and sex, in a highly homogenous cohort of young Romanians parenterally infected during early childhood. In total, 250 HIV participants were compared with age-matched HIV negative (HIV) controls (n = 72) in a cross-sectional study. After standardized neurocognitive, psychological testing and medical evaluation, linear regression was used to assess the effect of sex and HIV on neurocognitive outcomes. Study participants were on average 23 years old with balanced sex distribution (% women = 52% vs. 43%). HIV were more educated (12.7 vs. 11.6 years, P = 0.002).HIV status was associated with a lower global performance (β = -0.22, P < 0.001), after controlling for age and education. HIV women had better previous and current HIV-associated markers. The effect of HIV on global cognition did not differ between sexes in most cognitive domain...
Journal of Neuroimmunology, 2016
We evaluated the impact of latent toxoplasmosis (LT) on neurocognitive (NC) and neurobehavioural ... more We evaluated the impact of latent toxoplasmosis (LT) on neurocognitive (NC) and neurobehavioural functioning in young adults with and without chronic HIV infection, using a standardised NC test battery, self-reported Beck Depression Inventory, Frontal System Behaviour Scale, MINI-International Neuropsychiatric Interview and risk-assessment battery. 194 young adults (median age 24 years, 48.2% males) with chronic HIV infection (HIV+) since childhood and 51 HIV seronegative (HIV-) participants were included. HIV+ individuals had good current immunological status (median CD4: 479 cells/μL) despite a low CD4 nadir (median: 93 cells/μL). LT (positive anti-Toxoplasma IgG antibodies) was present in one third of participants. The impairment rates in the HIV-with and without Toxo were not significantly different (p=0.17). However, we observed an increasing trend (p<0.001) in impairment rates with HIV and LT status: HIV-/LT-(6.1%); HIV-/LT+ (22%), HIV+/LT-(31%), HIV+/LT+ (49%). In a multivariable analysis using the entire study group there were main effects on cognition for HIV and also for LT. Within the HIV+ group LT was associated with worse performance globally (p=0.006), in memory (p=0.009), speed of information processing (p=0.01), verbal (p=0.02) and learning (p=0.02) domains. LT was not associated with depressive symptoms, frontal systems dysfunction or risk behaviors in any of the groups. HIV participants with lower Toxoplasma antibody concentration had worse NC performance, with higher GDS values (p=0.03) and worse learning (p=0.002), memory (p=0.006), speed of information processing (p=0.01) T scores. Latent Toxoplasmosis may contribute to NC impairment in young adults, including those with and without chronic HIV infection.
Current Organic Chemistry, 2016
Hemoglobinopathies, such as β-thalassemia and sickle cell disease (SCD), are among the most commo... more Hemoglobinopathies, such as β-thalassemia and sickle cell disease (SCD), are among the most common congenital diseases in the world, with high mortality and morbidity rates. The most straightforward approach to correct the main culprit in hemoglobinopathies-the imbalance between the amounts of alpha-like globins/beta-like globins-will need to target directly the gene structure or their regulatory elements in order to obtain a sustained therapeutic effect. Finding effective methods to deliver the genetic " blueprints " of the correct and functional protein or, even better, the " DNA repairing kit " able to do the job in situ, remains a major challenge, despite the fact that gene therapy is already used in different diseases. Members of several viral families were employed as " Trojan horses " using the virus ability to deliver a modified genetic material inside the cell and to manipulate the host replication machinery to produce the encoded proteins. Recently, non-viral vectors are gaining advantages for genome correction, especially after the exponential development of the genome editing approaches that can provide precise in situ modifications. This review summarizes the recent advances in the viral and non-viral delivery strategies and emphasizes the therapeutic potential of different approaches designed to correct the genetic defects responsible for the most common hemoglobinopathies.
GERMS, 2015
Background The Romanian HIV epidemic is characterized by a high prevalence among children born in... more Background The Romanian HIV epidemic is characterized by a high prevalence among children born in the late '80s, perinatally infected. The impact of long-term treatment on their offspring is unknown. We evaluated the influence of prenatal care on the rate of premature birth among the HIV-exposed children of heavily treated HIV-infected mothers in two Romanian centers. Methods We retrospectively analyzed data on all patients born by HIV-infected mothers between 2006 and 2012 followed up in two main regional centers. We compared the rate of premature birth and the differences between the sites regarding children and maternal demographic characteristics and antiretroviral exposure in pregnant women. Results A total of 358 children born to 315 women were enrolled between 2006-2012, 262 children from the National Institute for Infectious Diseases "Prof. Dr. Matei Balș" Bucharest (NIID) and 96 children from the Clinical Infectious Diseases Hospital Constanța (IDHC). Gender rate in newborns and mean age in mothers were similar. We recorded statistically significant differences between centers in the rate of HIV vertical transmission (16.8% vs. 6.2%, p=0.002) and prematurity (25.2 vs. 14.6%, p=0.023). The most used antiretroviral combination during pregnancy in IDHC was boosted lopinavir and fixed dose zidovudine-lamivudine (66% of cases), while in NIID a greater diversity of antiretrovirals were used. Women from IDHC were more frequently treated during pregnancy (83.3% vs. 68.6%, p=0.004). HCV coinfection and illegal drug use were associated with prematurity in the NIID cohort (p=0.037, p=0.024). Conclusion We found a higher rate of premature birth and HIV infection in NIID. In IDHC we found a higher rate of low birth weight in children and a higher rate of heavily treated women. Prematurity was associated with hepatitis C infection and illegal drug use in the NIID cohort. Keywords HIV exposure, antiretroviral drugs, prematurity Background 1 Starting with 1990 Romania faced a particular HIV epidemic, characterized by a large number of
Romanian journal of virology
Hepatitis C is and will be a major public health concern. Confirmed infections were reported from... more Hepatitis C is and will be a major public health concern. Confirmed infections were reported from all Romanian counties but important differences between regions raise several explanations. Differences may reflect the different levels of testing, the performances of laboratories in confirming initially reactive samples or the risk factors higher prevalence. We have suggested that the prevalence of anti HCV infections can be a surrogate marker for the quality of parenteral medical or paramedical interventions. Present report identified additional problems in the surveillance of HCV infection in children. We screened 1787 samples from children hosted in orphanages (children under three years old) or in preschool children institutions (between 3-7 years old). We detected 31 repeatedly reactive samples with two EIA screening kits but confirmed only 8 in WB anti HCV. Four confirmed samples come from children under four months old suggesting maternally transmitted antibodies. In highly en...
Journal of medicine and life, Jan 14, 2011
The central nervous system can act as a compartment in which HIV can replicate independently from... more The central nervous system can act as a compartment in which HIV can replicate independently from plasma, and also as a sanctuary in which, under suboptimal drug pressure, HIV antiretroviral genetic variants can occur. Continuous replication of HIV in brain can contribute to neurocognitive impairment. Therefore, reaching adequate concentrations of antiretrovirals in the central nervous system might be essential in providing neuroprotection and improving neurocognition. Antiretrovirals have a restricted entry into the brain, due to several factors: the unique structure of the blood-brain barrier, and the existence of efficient efflux mechanisms. However, there is a high variability of antiretrovirals in reaching therapeutic drug concentrations in cerebrospinal fluid, that depend on the characteristics of the antiretrovirals (molecular weight, lipophilicity, protein binding) and on their capacity to be substrate for efflux transporters. The review aims to discuss the main mechanisms t...
Romanian journal of virology
Variability is a hallmark of HIV viruses both at the genetic and the phenotypic level. Viral sequ... more Variability is a hallmark of HIV viruses both at the genetic and the phenotypic level. Viral sequencing and phylogenetic analysis of many isolates revealed specific distribution of HIV-1 subtypes according to the geographic location and route of transmission. In Romania, the currently available data coming from the study of pediatric HIV infection suggest the predominance of subtype F. However, there are few data concerning the distribution of HIV-1 subtypes among adults. We investigated the changes in the distribution of different HIV-1 subtypes among HIV-1 infected adult patients from Bucharest over a 6 years period (1992-1998) by means of V3 binding assays. The analysis of the relative incidence of different HIV-1 serotypes revealed the steady predominance of serotype F (50-75%) among the adults from Bucharest and a small but constant increase of the number of samples with serotype B- from 5% in 1994 to 14% in 1998. In contrast, the serotype E is either absent or weakly represent...
Romanian biotechnological letters, 2011
BACKGROUND AND OBJECTIVE: As available data on HIV-1 strains from Romania indicate the prevalence... more BACKGROUND AND OBJECTIVE: As available data on HIV-1 strains from Romania indicate the prevalence of a particular subtype- F, not found in other European countries, we aimed at investigating the impact on drug susceptibility of mutations associated with drug resistance and their correlation with the virological and immune response to therapy. METHODS: 38 long term survivors, HIV-1 parenterally infected in childhood, with repeated virological failures, were genotyped for drug resistance and subtype determination. A phylogenetic tree of aligned reversetranscriptase sequences was built. RESULTS: 94.7% of all the patients'strains were subtype F1, clustering together with other Romanian and Angolan F1 strains. Despite the long and complex treatments, 15.8% of patients had wild type virus, 68.4% were fully susceptible to protease inhibitors, 47.3% to non-nucleoside reverstranscriptase inhibitors, 28.9% to nucleoside reverstranscriptase inhibitors. Only 13.2% were resistant to all anti...
BMC Infectious Diseases, 2014
Hepatitis Monthly, 2013
Background: Due to a recent alarming increase in the number of HIV-HCV co-infected patients in Ro... more Background: Due to a recent alarming increase in the number of HIV-HCV co-infected patients in Romania. Objectives: A cross sectional study was conducted to assess the baseline predictors of liver disease evolution. Patients and Methods: 83 HIV-HCV co-infected patients, untreated for HCV infection, were evaluated for viral replication, liver fibrosis (estimated by a noninvasive marker-FIB4), and plasma levels of IP-10 (interferon-gamma inducible protein 10)-a cytokine associated with an unfavorable outcome of HCV infection. Results: The median value for HCV viral load was high (6.3 log10 IU/mL), 98.8% of the patients were infected with HCV genotype 1. Although 53% of the patients received antiretroviral therapy (cART), only 31.8% of these achieved undetectable HIV levels. HCV viral load was significantly higher in patients with AIDS (6.4 vs. 6.1 log10IU/mL; P = 0.04), and in those naïve for cART (6.5 vs. 5.9 log10 IU/mL; P = 0.04). Severe fibrosis was directly correlated with immunosupression (56% vs. 17.4%, P = 0.03), HCV replication (6.1 vs. 4.9 log10IU/mL P = 0.008), and IP-10 median values (312 vs. 139 pg/ml, P=0.008). A serum IP-10 level higher than 400 pg/mL was significantly associated with FIB-4 median values (4.09 vs. 1.7, P = 0.004), HCV viral load (6.4 vs. 6.1 log10 IU/mL, P = 0.02) and ALT level (206.8 vs. 112.4 IU/L, P = 0.05). Conclusions: An important part of the HIV-HCV co-infected patients had negative baseline predictors for the evolution of HCV infection; their therapeutical management must be conducted with special attention towards adherence and potential overlapping drug toxicities. High concentrations of plasma IP-10 are reliable markers for the severity of liver disease.