Factors Influencing HIV Infection in Children Born to HIV-Infected Mothers in Turkey

Background: Human immunodeficiency virus (HIV) is still a challenge for children. About 15 to 45% of the HIV positive pregnant women can transmit the virus to their children during pregnancy, delivery and/or breastfeeding. The risk of transmission can be decreased my several measures. Aims: To identify factors associated with HIV infection in children born to HIV-infected mothers. Study Design: A multi-center retrospective cohort study. Methods: A ten-year retrospective cohort study in five dedicated HIV centers was conducted. The 325 women in our cohort were between the ages of 18 and 45. During the study period, 44 (13.5%) of these women gave birth and 51 babies were born. Of the 51 infants, 7 (13.7%) were HIV/AIDS positive. Results: Among the factors studied, breastfeeding, having a HIV-positive sibling and being on antiretroviral treatment during pregnancy and detectable HIV-RNA during delivery were found statistically significant. A multivariable logistic regression analysis showed that being on antiretroviral treatment during pregnancy is the most important predictor of mother-to-child transmission. Conclusion: Mother-to-child transmission appears to be an important route of HIV transmission in Turkey. Lack of antiretroviral treatment during pregnancy appears to be a key factor in transmission.

Efficacy and Safety of Direct-Acting Antivirals in Elderly Patients with Chronic Hepatitis C: A Nationwide Real-Life, Observational, Multicenter Study from Turkey.

BACKGROUND: The number and proportion of elderly patients living with chronic hepatitis C are expected to increase in the coming years. We aimed to compare the real-world efficacy and safety of direct-acting antiviral treatment in elderly and younger Turkish adults infected with chronic hepatitis C. METHODS: In this multicenter prospective study, 2629 eligible chronic hepatitis C patients treated with direct-acting antivirals between April 2017 and December 2019 from 37 Turkish referral centers were divided into 2 age groups: elderly (≥65 years) and younger adults (<65 years) and their safety was compared between 2 groups in evaluable population. Then, by matching the 2 age groups for demographics and pretreatment risk factors for a non-sustained virological response, a total of 1516 patients (758 in each group) and 1244 patients (622 in each group) from the modified evaluable population and per-protocol population were included in the efficacy analysis and the efficacy was compared between age groups. RESULTS: The sustained virological response in the chronic hepatitis C patients was not affected by the age and the presence of cirrhosis both in the modified evaluable population and per-protocol population (P = .879, P = .508 for modified evaluable population and P = .058, P = .788 for per-protocol population, respectively). The results of the per-protocol analysis revealed that male gender, patients who had a prior history of hepatocellular carcinoma, patients infected with non-genotype 1 hepatitis C virus, and patients treated with sofosbuvir+ribavirin had a significantly lower sustained virological response 12 rates (P < .001, P = .047, P = .013, and P = .025, respectively). CONCLUSION: Direct-acting antivirals can be safely used to treat Turkish elderly chronic hepatitis C patients with similar favorable efficacy and safety as that in younger adults.

Fibrosis scores that can be used in follow-up of after direct-acting antiviral treatment: APRI, FIB-4, King score and GUCI.

INTRODUCTION: Sustained virologic response in the treatment of chronic hepatitis C can be achieved with direct-acting antivirals (DAA) in recent years. Monitoring virologic and histologic response to treatment is essential and noninvasive methods are preferred. In our study, we aimed to determine the regression of fibrosis following DAA treatment with serum fibrosis indices constituting a noninvasive method. METHOD: Patients with chronic hepatitis C to whom DAA treatment is started between January 2016 and January 2018 in our clinic are evaluated retrospectively. The fibrosis scores [fibrosis 4 index (FIB-4), aminotransferase platelet ratio (APRI), Fibro QKing score, age platelet index, Goteburg University Cirrhosis Index (GUCI), aspartate transaminase/alanine transaminase ratio (AAR)] are calculated with routine biochemical and hematologic tests of DAA-treated patients before treatment, at the end of treatment, and in the 12th and 24th weeks of treatment. In total, the course of seven scores calculated at four separate times including baseline was recorded and compared. RESULTS: In total 91 patients are included in the study. The average age was 51.16 ± 13.78 and 59.3% (n = 54) of patients were women. According to the baseline FIB-4 values, the patients were grouped as cirrhotic or noncirrhotic, and 11 of them were cirrhotic (12.1%). Statistically significant regression in APRI, FIB-4, GUCI and King scores is seen in all groups regardless of their cirrhotic status, treatment experience or genotype (P < 0.001). Specified scores had a positive, significant correlation with pretreatment biopsy results [area under curve (AUC): 0.800, 0.782, 0.749 and 0.746]. CONCLUSION: APRI, FIB-4, GUCI and King scores that have a positive correlation with biopsy can also be used for fibrosis recovery follow-up after treatment with DAAs.

Adherence to Treatment with Oral Nucleoside/Nucleotide Analogs in Patients with Chronic Hepatitis B.

Objectives: Adherence to antiviral treatment is important for treatment success and prevention of resistance. It was aimed to determine treatment adherence to nucleoside/nucleotide analogs and factors influencing on adherence. Methods: The study included 168 patients who received oral nucleoside/nucleotide analog with diagnosis of chronic hepatitis for at least 1 year. Data regarding demographic characteristics and missed drug were collected using a survey, while list of medication within prior year were extracted from pharmacy registry and Medication Possession Rate (MPR) was calculated. Results: There were 60 women (35.7%) and 108 men (64.3%) in the study. Mean age was calculated as 43.61±10.35 years. It was found that 29.2% of patients were non-adherent based on MPR (MPR<0.90). It was observed that adherence was improved on middle age. Treatment adherence was found to be higher in patients receiving medication due to disorders other than hepatitis B. It was found that there was no significant difference in adherence according to age, gender, occupation status, marital status, smoking or alcohol consumption habits, type of antiviral treatment, time and mode of drug intake, and biopsy finding at time of drug prescription. The most common cause was identified as forgetfulness for missed drug. Other common causes were inoccupation and alteration in daily routine. Conclusion: In our study, the treatment adherence determined by MPR was 70.8%. This rate was lower than those reported for chronic hepatitis B in the literature. It is important to monitor and encourage treatment adherence in patients with chronic hepatitis B by clinicians.

Cognitive Assessment of Young Adults Before and After Initiation of Combination Antiretroviral Therapy.

Objective: In the determination and monitoring of neurocognitive disorders in human immunodeficiency virus (HIV)-positive individuals, there is a need for significantly more practical methods which provide results in a shorter time than the tests that require challenging and specialized expertise. This study aimed to evaluate cognitive functions and the factors affecting them in naïve HIV-positive patients using by Montreal Cognitive Assessment (MoCA) test before and after the initiation of combination antiretroviral therapy. Materials and Methods: HIV-positive, treatment-naïve patients monitored between January-June 2017 were included in the study. The MoCA test was performed at the beginning and the sixth month of the treatment. Results: Forty male patients were included in the study. The mean age was calculated as 29.1±4.0. When the factors affecting the MoCA score were examined, there was a significant relationship between the education level and the MoCA score. Smoking, using alcohol, and substance did not have a significant impact on baseline MoCA values. A significant correlation was found between cluster differentiation 4 (CD4) count and HIV RNA level and attention function. There was a significant increase in the total MoCA score and the MoCA subgroup scores at the end of the sixth month of the treatment. Conclusion: MoCA test is one of the most practical tests that can be applied in a short time period, and it was found useful in evaluating the changes in the cognitive functions of HIV-positive patients during antiretroviral treatment.

Prevalence and mortality of cancer among people living with HIV and AIDS patients: a large cohort study in Turkey.

BACKGROUND: Cancer is responsible for elevated human immunodeficiency virus (HIV)-related mortality but there are insufficient data about cancer in HIV-positive patients in Turkey. AIMS: We aimed to investigate the prevalence and mortality of cancer among people living with HIVand AIDS patients in Istanbul, Turkey. METHODS: Between January 1998 and December 2016, people living with HIVand AIDS patients were enrolled in this study by the ACTHIV-IST Study Group, which consists of 5 centres to follow-up HIV-positive patients in Istanbul. The cancer diagnoses included AIDS-defining cancers (ADCs) and non AIDS-defining cancers (NADCs). RESULTS: Among 1872 patients, 37 (1.9%) were diagnosed with concurrent cancer. Eleven patients were diagnosed during follow-up; the prevalence of cancer among people living with HIVand AIDS patients was 2.6%. Among 48 cancer patients, 35 patients had ADCs, and 32 of them were diagnosed at their first hospital admission. There were 1007 late presenters and 39 of them had cancer (29 were ADCs). The most prevalent NADCs were gastrointestinal, genitourinary, and pulmonary cancers. NADCs were mostly diagnosed during follow-up of patients. The mortality of this group was significantly higher than that of patients with ADCs (53.9% vs 22.9%). CONCLUSIONS: These results indicate the importance of cancer screening at diagnosis and during follow-up of HIV infection. A detailed physical examination contributes to diagnosis of the most prevalent ADCs (Kaposi's sarcoma and non-Hodgkin's lymphoma), especially in late presenters. For NADCs, individual risk factors should be considered.

Diagnostic accuracy of different noninvasive scores for detecting advanced fibrosis in chronic hepatitis B.

OBJECTIVES: The liver biopsy is the gold standard for determining the level of fibrosis in chronic hepatitis B infection (CHBI). Nonetheless, it is possible to predict liver fibrosis through some noninvasive methods such as noninvasive scoring (NIS) of some serum biomarkers obtained from routine blood tests. We aimed to evaluate the diagnostic accuracy of nine NIS for detecting advanced fibrosis in CHBI. PATIENTS AND METHODS: We reviewed the hospital records of CHBI cases with liver biopsy between January 2011 and December 2016 retrospectively. Using Ishak scoring method, we classified fibrosis stage 1-2 as mild and 3-6 as advanced fibrosis. We calculated the NIS by considering the age, platelet count, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltransferase, platelet, and international normalized ratio values at the time of the biopsy. RESULTS: The mean age of 202 patients was 37.69± 11.33 years. In cases with advanced fibrosis, the age, gammaglutamyltransferase, and international normalized ratio values were higher and platelet count was lower (P < 0.05). Mean platelet volume was not different between the two groups (P = 0.499). The median values of γ-glutamyl peptidase-platelet ratio (GPR), FibroQ, Goteborg University Cirrhosis Index, fibrosis-4 (FIB-4), aspartate aminotransferase-platelet ratio index, age-platelet index, and King scoring were significantly higher in the advanced fibrosis group. The highest area under the curve value was in GPR [AUC = 0.731 (0.639-0.788); P = 0.000] in the receiver operating characteristic curve analysis. Cirrhosis Discriminant Score and Aspartate aminotransferase-to-alanine aminotransferase ratio tests were not valuable in detecting advanced fibrosis. FIB-4 had the highest (0.678) diagnostic accuracy rate. CONCLUSION: We found that the calculation of NIS before liver biopsy, especially GPR and FIB-4, may be useful for predicting advanced fibrosis in cases with CHBI.

Genotypes of hepatitis a virus in Turkey: first report and clinical profile of children infected with sub-genotypes IA and IIIA.

BACKGROUND: Hepatitis A virus (HAV) is a food and water-borne virus causing clinical (mainly hepatitis) and subclinical disease in humans. It is important to characterize circulating strains of HAV in order to prevent HAV infections using efficacious vaccines. The aim of this study was the detection and characterization of the circulating strains of HAV in Turkey by performing serology, RT-PCR, sequencing and phylogenetic analysis. METHODS: In this study, 355 HAV suspected cases were analysed by ELISA for the presence of antibodies to HAV. RNA was extracted from 54 HAV IgM positive human sera. None of the suspect cases were vaccinated against HAV and they never received blood transfusions. Samples found positive by RT-PCR using primers targeting the VP1/VP2A junction and VP1/VP3 capsid region of HAV, were subjected to sequencing and phylogenetic analyses. RESULTS: IgM type antibodies to HAV were detected in 54 patients. Twenty one of them were students. The age of IgM positive cases was between 3 and 60 years. IgM positivity differed in age groups and was higher in the age group 3 to 10 years. Phylogenetic analysis showed that the majority of HAV strains detected in this study belong to the "HAV 1B" cluster. In addition, the HAV sub-genotypes IA (KT874461.1) and IIIA (KT222963.1) were found in 2 children. These sub-genotypes were not previously reported in Turkey. The child who carried sub-genotype IIIA travelled to Afghanistan and presented with abdominal pain, icterus and vomitus. He was positive for anti-HAV IgM and IgG but negative for hepatitis B and C. Liver enzymes like aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma-glutamyl transferase and lactate dehydrogenase were severely elevated. Bilirubin levels were also increased. White blood cells, neutrophils and hemoglobin were decreased while lymphocytes and monocytes were increased. Similar clinical signs and laboratory findings were reported for the child infected with sub-genotype IA but aspartate aminotransferase and alanine aminotransferase were not severely elevated. CONCLUSIONS: The results indicate that molecular studies determining the HAV genotype variation in Turkey are timely and warranted. The majority of IgM positive cases in 3-10 year old patients indicate that childhood vaccination is important. Sub-genotype IB is the most prevalant genotype in Turkey. Surprisingly, sub-genotype IA and IIIA are also present in Turkey; future diagnostic efforts need to include diagnostic methods which can identify this emerging HAV genotypes. Our results also show that one important risk factor for contracting hepatitis A virus is international travel since genotype IIIA was detected in a child who had travelled to Afghanistan.

An Evaluation of Surgical Prophylaxis Procedures in Turkey: A Multi-Center Point Prevalence Study.

OBJECTIVE: The purpose of this study was to evaluate compliance with guidelines in surgical prophylaxis (SP) procedures in Turkey. MATERIALS AND METHODS: A point prevalence study involving 4 university, 5 education and research and 7 public hospitals was performed assessing compliance with guidelines for antibiotic use in SP. Compliance was based on the "Clinical Practice Guidelines for Antimicrobial Surgery (CPGAS) 2013" guideline. RESULTS: Sixteen centers were included in the study, with 166 operations performed at these being evaluated. Parenteral antibiotic for SP was applied in 161 (96.9%) of these. Type of antibiotic was inappropriate in 66 (40.9%) cases and duration of use in 47 (29.1%). The main antibiotics used inappropriately in SP were ceftriaxone, glycopeptides and aminoglycosides. No significant difference was observed between secondary and tertiary hospitals in terms of inappropriate selection. Duration of prophylaxis was also incompatible with guideline recommendations in approximately half of surgical procedures performed in both secondary and tertiary hospitals, however statistical significance was observed between institutions in favor of tertiary hospitals. CONCLUSION: Antibiotics are to a considerable extent used in a manner incompatible with guidelines even in tertiary hospitals in Turkey. It must not be forgotten that several pre-, intra- and postoperative factors can be involved in the development of surgical site infections (SSI), and antibiotics are not the only option available for preventing these. A significant improvement can be achieved in prophylaxis with close observation, educational activities, collaboration with the surgical team and increasing compliance with guidelines. All health institutions must establish and apply their own SP consensus accompanied by the guidelines in order to achieve success in SP.

Serum soluble urokinase-type plasminogen activator receptor and interferon-γ-induced protein 10 levels correlate with significant fibrosis in chronic hepatitis B.

BACKGROUND: Hepatitis B virus (HBV) presents an important public health problem. Liver biopsy is currently the gold standard for assessing the degree of intrahepatic inflammation and for staging liver fibrosis. However, the value of liver biopsies is limited by sampling errors, understaging and interobserver variability in interpretation. There is, therefore, a need to identify novel, non-invasive serologic biomarkers for the development of new predictive models of fibrosis. METHODS: We enrolled patients with chronic hepatitis B infection (CHB) and examined the relationships between serum soluble urokinase plasminogen activator receptor (suPAR) and interferon-induced protein-10 (IP-10), and the results of liver biopsies. Healthy volunteers with normal aminotransferase levels and negative serological results for HBV, hepatitis C virus and human immunodeficiency virus were recruited as controls. RESULTS: Mean platelet volume, serum suPAR and IP-10 were significantly elevated in patients with CHB compared with controls. Median serum suPAR and IP-10 levels were significantly higher in patients with liver fibrosis compared with patients with mild fibrosis. There was no significant difference in mean platelet volume or aspartate aminotransferase-to-platelet ratio index scores between patients with mild and significant fibrosis. CONCLUSION: suPAR and IP-10 were able to distinguish between significant and mild fibrosis with good sensitivity and specificity, and may thus represent useful biomarkers for identifying patients with significant fibrosis.

Predictors of fatality in pandemic influenza A (H1N1) virus infection among adults.

BACKGROUND: The fatality attributed to pandemic influenza A H1N1 was not clear in the literature. We described the predictors for fatality related to pandemic influenza A H1N1 infection among hospitalized adult patients. METHODS: This is a multicenter study performed during the pandemic influenza A H1N1 [A(H1N1)pdm09] outbreak which occurred in 2009 and 2010. Analysis was performed among laboratory confirmed patients. Multivariate analysis was performed for the predictors of fatality. RESULTS: In the second wave of the pandemic, 848 adult patients were hospitalized because of suspected influenza, 45 out of 848 (5.3%) died, with 75% of fatalities occurring within the first 2 weeks of hospitalization. Among the 241 laboratory confirmed A(H1N1)pdm09 patients, the case fatality rate was 9%. In a multivariate logistic regression model that was performed for the fatalities within 14 days after admission, early use of neuraminidase inhibitors was found to be protective (Odds ratio: 0.17, confidence interval: 0.03-0.77, p=0.022), nosocomial infections (OR: 5.7, CI: 1.84-18, p=0.013), presence of malignant disease (OR: 3.8, CI: 0.66-22.01, p=0.133) significantly increased the likelihood of fatality. CONCLUSIONS: Early detection of the infection, allowing opportunity for the early use of neuraminidase inhibitors, was found to be important for prevention of fatality. Nosocomial bacterial infections and underlying malignant diseases increased the rate of fatality.

Epidemiological profile of naive HIV-1/AIDS patients in Istanbul: the largest case series from Turkey.

The aim of the study was to report the epidemiological profile of HIV-1 positive patients from, Istanbul, Turkey, which has one of the lowest HIV-1/AIDS prevalences in Europe. The patients were followed by ACTHIV-IST group which was established by the Infectious Diseases Departments of five teaching hospitals (three university hospitals and two public hospitals) in Istanbul, Turkey. The HIV-1 positive patients were added to the standard patient files in all of the centers; these files were then transferred to the ACTHIV-IST database in the Internet. A total of 829 naiv-untreated HIV-1 positive patients were chosen from the database. The number of male patients was 700 (84.4%) and the mean age of the patients was 37 years (range, 17-79). In our study group 348 (42%) of the patients were married and 318 (38.7%) of the patients were single. The probable route of transmission was heterosexual intercourse in 437 (52.7%) patients and homosexual intercourse in 256 (30.9%) patients. In 519 (62.6%) patients the diagnose was made due to a screening test and in 241 (29.1%) patients, the diagnose was made due to an HIV-related/non-related disease. The mean CD4+ T cell number in 788 of the patients was 357.8/mm(3) (±271.1), and the median viral load in 698 of the patients was 100,000 copies/mL (20-9,790,000). In Turkey, the number of HIV-1 positive patients is still low and to diagnose with a screening test is the most common way of diagnostic route.