Efficacy and safety of an inactivated whole-virion SARS-CoV-2 vaccine (CoronaVac): interim results of a double-blind, randomised, placebo-controlled, phase 3 trial in Turkey.

BACKGROUND: CoronaVac, an inactivated whole-virion SARS-CoV-2 vaccine, has been shown to be well tolerated with a good safety profile in individuals aged 18 years and older in phase 1/2 trials, and provided a good humoral response against SARS-CoV-2. We present the interim efficacy and safety results of a phase 3 clinical trial of CoronaVac in Turkey. METHODS: This was a double-blind, randomised, placebo-controlled phase 3 trial. Volunteers aged 18-59 years with no history of COVID-19 and with negative PCR and antibody test results for SARS-CoV-2 were enrolled at 24 centres in Turkey. Exclusion criteria included (but were not limited to) immunosuppressive therapy (including steroids) within the past 6 months, bleeding disorders, asplenia, and receipt of any blood products or immunoglobulins within the past 3 months. The K1 cohort consisted of health-care workers (randomised in a 1:1 ratio), and individuals other than health-care workers were also recruited into the K2 cohort (randomised in a 2:1 ratio) using an interactive web response system. The study vaccine was 3 µg inactivated SARS-CoV-2 virion adsorbed to aluminium hydroxide in a 0·5 mL aqueous suspension. Participants received either vaccine or placebo (consisting of all vaccine components except inactivated virus) intramuscularly on days 0 and 14. The primary efficacy outcome was the prevention of PCR-confirmed symptomatic COVID-19 at least 14 days after the second dose in the per protocol population. Safety analyses were done in the intention-to-treat population. This study is registered with ClinicalTrials.gov (NCT04582344) and is active but no longer recruiting. FINDINGS: Among 11 303 volunteers screened between Sept 14, 2020, and Jan 5, 2021, 10 218 were randomly allocated. After exclusion of four participants from the vaccine group because of protocol deviations, the intention-to-treat group consisted of 10 214 participants (6646 [65·1%] in the vaccine group and 3568 [34·9%] in the placebo group) and the per protocol group consisted of 10 029 participants (6559 [65·4%] and 3470 [34·6%]) who received two doses of vaccine or placebo. During a median follow-up period of 43 days (IQR 36-48), nine cases of PCR-confirmed symptomatic COVID-19 were reported in the vaccine group (31·7 cases [14·6-59·3] per 1000 person-years) and 32 cases were reported in the placebo group (192·3 cases [135·7-261·1] per 1000 person-years) 14 days or more after the second dose, yielding a vaccine efficacy of 83·5% (95% CI 65·4-92·1; p<0·0001). The frequencies of any adverse events were 1259 (18·9%) in the vaccine group and 603 (16·9%) in the placebo group (p=0·0108) with no fatalities or grade 4 adverse events. The most common systemic adverse event was fatigue (546 [8·2%] participants in the vaccine group and 248 [7·0%] the placebo group, p=0·0228). Injection-site pain was the most frequent local adverse event (157 [2·4%] in the vaccine group and 40 [1·1%] in the placebo group, p<0·0001). INTERPRETATION: CoronaVac has high efficacy against PCR-confirmed symptomatic COVID-19 with a good safety and tolerability profile. FUNDING: Turkish Health Institutes Association.

Evaluation of kidney function tests in HIV-positive patients receiving combined antiretroviral therapy.

INTRODUCTION: Human immunodeficiency virus is a chronic infection that attacks the immune system of the human body, particularly CD4 T lymphocytes. Combined antiretroviral therapies are highly effective in virological suppression of human immunodeficiency virus infection. It has been shown that some retroviral therapies have a higher nephrotoxicity potential. As a result of renal injury, serum creatinine increases and the estimated glomerular filtration rate is reduced. The aim of our study was to assess changes in kidney function during a 24-month period in HIV-positive patients who were begun on combined antiretroviral therapy. MATERIAL AND METHODS: A total of 127 HIV-positive patients were enrolled. The patients were divided into five groups; patients who received no therapy were designated as group 1; those who received Dolutegravir/Abacavir/Lamivudine combination as group 2; those who received Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide Fumarate combination as group 3; those who received Emtricitabine/Tenofovir Disoproxil Fumarate/Dolutegravir combination as group 4; and those who received Emtricitabine/Tenofovir Disoproxil Fumarate/Raltegravir combination as group 5. We compared the effects of these drugs on estimated glomerular filtration rate during a 24-month follow-up period. RESULTS: At the 24th month of therapy, a significant difference was observed between the estimated glomerular filtration rate (eGFR) levels of the study groups (P < .001). eGFR level was significantly higher in group 4 compared with groups 1, 2 and 3 (P = .009, P < .001, P < .001, respectively), whereas it was significantly lower in group 5 than groups 1, 2 and 3 (P = .005, P < .001, P < .001, respectively). No significant eGFR difference was found between group 4 and group 5 (P > .05). Serum creatinine level was significantly higher in groups 4 and 5 compared with the other groups (P < .001). CONCLUSION: The use of TDF-containing regimens causes renal dysfunction. Therefore, we recommend close monitoring of renal function, especially in patients treated with TDF.

Serum TNF-α, IL-1ß, and IL-6 levels in chronic HBV-infected patients.

BACKGROUND: The objective of the study was to evaluate the serum levels of tumour necrosis factor (TNF)-α, interleukin (IL)-1ß and IL-6 in chronic HBV-infected patients. METHODS: The present study was a single centre, prospective and randomised controlled trial. Twenty healthy volunteers and thirty HBeAg-negative patients with planned liver biopsy and treatment-naive diagnosed with chronic hepatitis B (CHB) were included in the study. TNF-α, IL-1ß and IL-6 levels were measured in the serum of CHB patient and control groups using an ELISA. Results were compared statistically using a Mann-Whitney U test. RESULTS: The mean age of the CHB group (20 men, 10 women) and the control group (10 men, 10 women) was 33.3 ± 9.7 (17-55) and 26.1 ± 12.3 (16-57), respectively. When the two groups were compared with the Mann-Whitney U-test, TNF-α and IL-6 levels were found to be significantly higher in the CHB group compared to the control group (P = .003, P < .0001, respectively). Although IL-1ß levels were not statistically significant, they were higher in the CHB group compared to the controls (P = .07). CONCLUSIONS: The results of our study showed that serum levels of TNF-α and IL-6 are increased in CHB patients.

Occult hepatitis B infection in Turkish HIV-infected patients: A multicentre, retrospective, cross-sectional study, Schindler study.

OBJECTIVE: Occult hepatitis B infection (OHBI) appears to have a higher prevalence in populations at high risk for hepatitis B virus (HBV) infection with concomitant liver disease. The aim was to assess the prevalence of OHBI in a sample of human immunodeficiency virus -1 positive and HBV surface antigen-negative (HIV-1+/HBsAg-) Turkish patients. METHODS: Ten centres in Turkey were included in the study. Patients were selected on the basis of a power calculation with a known population size of HIV-positive patients and a reported prevalence of OHBI. Gender, age, occupation, place of residence, treatment and clinical status, and laboratory results, including immunodeficiency panel, antibody tests, hemogram, biochemistry, and coagulation studies were evaluated retrospectively. RESULTS: The number of HIV-infected patients followed in these centres was 3172 and the sample population numbered 278. All 278 were HBsAg negative. The mean age of the sample was 37.2 ± 13.1 years and 235 (84.5%) were male. All but one patient (99.6%) had been treated with antiretroviral therapy. Of the 278 patients, 169 (60.6%) were positive for Anti-HBs and 125 (44.8%) were positive for Anti-HBc IgG. HIV RNA was detected in 203/278 (73%) of the patients. Four HBV DNA (1.4%) were diagnosed with OHBI. There was no significant difference in hemogram, hemoglobin or bilirubin concentrations in those with OHBI compared with the other patients. CONCLUSION: In a representative sample of HIV+ patients from 10 Turkish centres, the prevalence of OHBI was found to be 1.4%. In HIV positive patients, it is important to identify those with OHBI for optimal clinical management and prognosis.

Predictors of unfavorable outcome in neurosyphilis: Multicenter ID-IRI Study.

Neurosyphilis (NS) has different clinical manifestations and can appear during any stage of syphilis. We aimed to identify the factors affecting poor outcome in NS patients. Patients with positive cerebrospinal fluid Venereal Disease Research Laboratory test, and positive serological serum treponemal or nontreponemal tests were classified as definite NS. The data of 141 patients with definite NS were submitted from 22 referral centers. Asymptomatic NS, syphilitic meningitis, meningovascular syphilis, tabes dorsalis, general paresis, and taboparesis were detected in 22 (15.6%), 67 (47.5%), 13 (9.2%), 10 (7%), 13 (9.2%), and 16 patients (11.3%), respectively. The number of HIV-positive patients was 43 (30.4%). The most common symptoms were headache (n = 55, 39%), fatigue (n = 52, 36.8%), and altered consciousness (50, 35.4%). Tabetic symptoms were detected in 28 (19.8%), paretic symptoms in 32 (22.6%), and vascular symptoms in 39 patients (27.6%). Eye involvement was detected in 19 of 80 patients (23.7%) who underwent eye examination and ear involvement was detected in eight of 25 patients (32%) who underwent ear examination. Crystallized penicillin was used in 109 (77.3%), procaine penicillin in seven (4.9%), ceftriaxone in 31 (21.9%), and doxycycline in five patients (3.5%). According to multivariate regression analysis, while headache was a protective factor in NS patients, double vision was significantly associated to poor outcome. We concluded that double vision indicated unfavorable outcome among NS patients. A high clinical suspicion is needed for the diagnosis NS. As determined in our study, the presence of headache in syphilitic patients can help in early diagnosis of central nervous system disease.

Current status of HIV/AIDS-syphilis co-infections: a retrospective multicentre study.

OBJECTIVE: Treponema pallidum and HIV are transmitted frequently through sexual contact, these agents with epidemiological similarities co-infect the same host. The current number of HIV-infected cases in Turkey is increasing. For this reason, we aimed to reveal the characteristics of syphilis in HIV/AIDS cases. METHODS: A retrospective longitudinal cohort study was performed, patients were followed up at 24 clinics in 16 cities from all seven regions of Turkey between January 2010 to April 2018. We examined the socio-demographic characteristics, laboratory parameters and neurosyphilis association in HIV/AIDS-syphilis co-infected cases. RESULTS: Among 3,641 patients with HIV-1 infection, 291 (8%) patients were diagnosed with syphilis co-infection. Most patients were older than 25 years (92%), 96% were males, 74% were working, 23% unemployed, and 3% were students. The three highest prevalence of syphilis were in Black Sea (10.3%), Mediterranean (8.4%) and Marmara Regions (7.4%). As for sexual orientation, 46% were heterosexuals, 42% men who have sex with men (MSM), and no data available for 12%. Patients with the number of CD4+ ≤ 350 mm3 reached 46%, 17% of the patients received antiretroviral therapy and neurosyphilis association reached 9%. CONCLUSION: Although HIV/AIDS-syphilis co-infection status appeared high in heterosexuals, MSM had a moderate level increase in cases. Our results suggested syphilis co-infection in HIV/AIDS cases should be integral part of monitoring in a national sexual transmitted diseases surveillance system. However, our data may provide base for HIV/syphilis prevention and treatment efforts in the future.

96 weeks treatment of tenofovir alafenamide vs. tenofovir disoproxil fumarate for hepatitis B virus infection.

BACKGROUND & AIMS: Tenofovir alafenamide (TAF) is a new prodrug of tenofovir developed to treat patients with chronic hepatitis B virus (HBV) infection at a lower dose than tenofovir disoproxil fumarate (TDF) through more efficient delivery of tenofovir to hepatocytes. In 48-week results from two ongoing, double-blind, randomized phase III trials, TAF was non-inferior to TDF in efficacy with improved renal and bone safety. We report 96-week outcomes for both trials. METHODS: In two international trials, patients with chronic HBV infection were randomized 2:1 to receive 25 mg TAF or 300 mg TDF in a double-blinded fashion. One study enrolled HBeAg-positive patients and the other HBeAg-negative patients. We assessed efficacy in each study, and safety in the pooled population. RESULTS: At week 96, the differences in the rates of viral suppression were similar in HBeAg-positive patients receiving TAF and TDF (73% vs. 75%, respectively, adjusted difference -2.2% (95% CI -8.3 to 3.9%; p = 0.47), and in HBeAg-negative patients receiving TAF and TDF (90% vs. 91%, respectively, adjusted difference -0.6% (95% CI -7.0 to 5.8%; p = 0.84). In both studies the proportions of patients with alanine aminotransferase above the upper limit of normal at baseline, who had normal alanine aminotransferase at week 96 of treatment, were significantly higher in patients receiving TAF than in those receiving TDF. In the pooled safety population, patients receiving TAF had significantly smaller decreases in bone mineral density than those receiving TDF in the hip (mean % change -0.33% vs. -2.51%; p <0.001) and lumbar spine (mean % change -0.75% vs. -2.57%; p <0.001), as well as a significantly smaller median change in estimated glomerular filtration rate by Cockcroft-Gault method (-1.2 vs. -4.8 mg/dl; p <0.001). CONCLUSION: In patients with HBV infection, TAF remained as effective as TDF, with continued improved renal and bone safety, two years after the initiation of treatment. Clinicaltrials.gov number: NCT01940471 and NCT01940341. LAY SUMMARY: At week 96 of two ongoing studies comparing the efficacy and safety of tenofovir alafenamide (TAF) to tenofovir disoproxil fumarate (TDF) for the treatment of chronic hepatitis B patients, TAF continues to be as effective as TDF with continued improved renal and bone safety. Registration: Clinicaltrials.gov number: NCT01940471 and NCT01940341.

Cranial imaging findings in neurobrucellosis: results of Istanbul-3 study.

OBJECTIVE: Neuroimaging abnormalities in central nervous system (CNS) brucellosis are not well documented. The purpose of this study was to evaluate the prevalence of imaging abnormalities in neurobrucellosis and to identify factors associated with leptomeningeal and basal enhancement, which frequently results in unfavorable outcomes. METHODS: Istanbul-3 study evaluated 263 adult patients with CNS brucellosis from 26 referral centers and reviewed their 242 magnetic resonance imaging (MRI) and 226 computerized tomography (CT) scans of the brain. RESULTS: A normal CT or MRI scan was seen in 143 of 263 patients (54.3 %). Abnormal imaging findings were grouped into the following four categories: (a) inflammatory findings: leptomeningeal involvements (44), basal meningeal enhancements (30), cranial nerve involvements (14), spinal nerve roots enhancement (8), brain abscesses (7), granulomas (6), and arachnoiditis (4). (b) White-matter involvement: white-matter involvement (32) with or without demyelinating lesions (7). (c) Vascular involvement: vascular involvement (42) mostly with chronic cerebral ischemic changes (37). (d) Hydrocephalus/cerebral edema: hydrocephalus (20) and brain edema (40). On multivariate logistic regression analysis duration of symptoms since the onset (OR 1.007; 95 % CI 1-28, p = 0.01), polyneuropathy and radiculopathy (OR 5.4; 95 % CI 1.002-1.013, p = 0.044), cerebrospinal fluid (CSF)/serum glucose rate (OR 0.001; 95 % CI 000-0.067, p = 0.001), and CSF protein (OR 2.5; 95 % CI 2.3-2.7, p = 0.0001) were associated with diffuse inflammation. CONCLUSIONS: In this study, 45 % of neurobrucellosis patients had abnormal neuroimaging findings. The duration of symptoms, polyneuropathy and radiculopathy, high CSF protein level, and low CSF/serum glucose rate were associated with inflammatory findings on imaging analyses.

Risk factors for relapse after discontinuation of tenofovir or entecavir in hepatitis B e antigen-negative patients.

Background and Aim: This study aimed to define the relapse frequency and risk determinants in chronic hepatitis B (CHB) patients who discontinued nucleoside analog (NA) treatment, were HBeAg-negative, and had achieved both a virological and biochemical response. Materials and Methods: This retrospective cohort study reviewed patients with HBeAg-negative CHB who received antiviral therapy for at least 65 months between January 1, 2013, and December 31, 2020. These patients discontinued treatment after demonstrating a biochemical and virological response and were evaluated at 6, 12, and 24 months post-treatment discontinuation. Results: Sixty-seven patients with CHB who received NA therapy for at least 65 months, discontinued treatment, and had undetectable HBV DNA and normal ALT values were evaluated. After cessation of NA therapy, a relapse was observed in 38 patients (56.7%). The relapse rate was 71.0% in patients treated with tenofovir disoproxil fumarate (TDF) as the last NA type and 37.9% in patients treated with entecavir (ETV) (p=0.017). The cutoff value for the best estimate of age for predicting relapse was 42 years. The relapse rate was 69.2% in patients aged ≥42 years and 39.2% in patients aged <42 years (p=0.007). The relapse rate was 51.3% in patients with a pre-treatment fibrosis score of 2, 56.0% in those with a fibrosis score of 3, and 100% in those with a fibrosis score of 4 (p=0.089). Conclusion: Among HBeAg-negative CHB patients who achieved a virological and biochemical response to long-term antiviral therapy, those aged 42 years and older, those with high fibrosis scores before treatment, and those who used TDF before treatment cessation should be closely monitored for relapse, especially in the first 12 months after stopping NA treatment.

Evaluation of chronic hepatitis B patients who voluntarily discontinued oral antiviral therapy: is there an answer to the controversial topic?

OBJECTIVE: The uncertain treatment duration for nucleos(t)ide analogues (NA) used in the treatment of chronic hepatitis B (CHB) is an important problem for both patients and physicians. The aim of this study was to evaluate the determinants of virologic relapse (VR) and the optimum time of treatment discontinuation in the follow-up of CHB patients who voluntarily discontinued treatment after virological suppression was achieved under NA use. METHODS: Data from 138 patients from 11 centers were included in this registry-based study. Factors associated with VR were investigated using multivariate Cox regression analysis. RESULTS: Ninety-nine (71.7%) of the patients were HBeAg (Hepatitis B e antigen) negative. During the 24-month follow-up period after treatment discontinuation, VR occurred in 58.7% (n = 81) of all patients and 57.6% (n = 57) of HBeAg-negative patients. The duration of NA treatment was significantly shorter (cutoff 60 months) in HBeAg-negative patients who later developed VR. In addition, the duration of virologic remission achieved under NA treatment was significantly shorter (cutoff 52 months) in those who later developed VR. In the Cox multivariate regression model of HBeAg-negative patients, having less than 60 months of NA treatment (HR = 2.568; CI:1.280-5.148; P  = 0.008) and the levels of alanine aminotransferase being equal to or higher than twice the upper level of normal at the beginning of treatment (HR = 3.753; CI:1.551-9.081; P  = 0.003) were found to be statistically significant and independently associated with VR. CONCLUSION: The findings of this study may provide clinical guidance in terms of determining the most appropriate discontinuation time for NA.

Comparison of Immunological and Virological Recovery with Rapid, Early, and Late Start of Antiretroviral Treatment in Naive Plwh: Real-World Data.

Background: Rapid initiation of antiretroviral therapy (ART) reduces the transmission of HIV infection in the community. This study aimed to determine whether rapid ART initiation is effective compared to standard ART treatment in our country. Methods: Patients were grouped based on time to treatment initiation. HIV RNA levels, CD+4 T cell count, CD4/CD8 ratio, and ART regimens were recorded at baseline and follow-up visits for 12 months. Results: There were 368-ART naive adults (treatment initiated at the time of HIV diagnosis; 143 on the first day, 48 on the second-seventh day, and 177 after the seventh day). Although virological suppression rates at 12th months were higher in all groups, over 90% on average, there were no statistically significant differences in HIV-1 RNA suppression rates, CD+4 T cell count, and CD4/CD8 ratio normalization in the studied months but in multivariate logistic regression analysis; showed a significant correlation between both virological and immunological response and those with CD4+ T <350 cells/mL at 12th month in total patients. Conclusion: Our findings support the broader application of recommendations for rapid ART initiation in HIV patients.

First year real life experience with tenofovir alafenamide fumarate: The pythagorean cohort.

Background and Aim: In chronic hepatitis B infection, antiviral therapy significantly reduces the incidence of complications. This study aimed to present real-life 12-month effectiveness and safety data for TAF. Materials and Methods: This Pythagoras Retrospective Cohort Study included patients from 14 centers in Turkiye. The study presents 12-month results of 480 patients treated with TAF as initial therapy or after switching from another antiviral drug. Results: The study shows treatment of about 78.1% patients with at least one antiviral agent (90.6% tenofovir disoproxil [TDF]). The rate of undetectable HBV DNA increased in both treatment-experienced and naive patients. In TDF-experienced patients, the rate of alanine transaminase (ALT) normalization increased slightly (1.6%) within 12 months, but the change was not statistically significant (p=0.766). Younger age, low albumin, and high body mass index and cholesterol were identified as risk factors for abnormal ALT after 12 months, but no linear relationship was detected. In TDF-experienced patients, renal and bone function indicators showed significant improvement three months after the transition to TAF and remained stable for 12 months. Conclusion: Real-life data demonstrated effective virological and biochemical responses with TAF therapy. After switching to TAF treatment, gains in kidney and bone functions were achieved in the early period.

Efficacy and tolerability of antibiotic combinations in neurobrucellosis: results of the Istanbul study.

No data on whether brucellar meningitis or meningoencephalitis can be treated with oral antibiotics or whether an intravenous extended-spectrum cephalosporin, namely, ceftriaxone, which does not accumulate in phagocytes, should be added to the regimen exist in the literature. The aim of a study conducted in Istanbul, Turkey, was to compare the efficacy and tolerability of ceftriaxone-based antibiotic treatment regimens with those of an oral treatment protocol in patients with these conditions. This retrospective study enrolled 215 adult patients in 28 health care institutions from four different countries. The first protocol (P1) comprised ceftriaxone, rifampin, and doxycycline. The second protocol (P2) consisted of trimethoprim-sulfamethoxazole, rifampin, and doxycycline. In the third protocol (P3), the patients started with P1 and transferred to P2 when ceftriaxone was stopped. The treatment period was shorter with the regimens which included ceftriaxone (4.40 ± 2.47 months in P1, 6.52 ± 4.15 months in P2, and 5.18 ± 2.27 months in P3) (P = 0.002). In seven patients, therapy was modified due to antibiotic side effects. When these cases were excluded, therapeutic failure did not differ significantly between ceftriaxone-based regimens (n = 5/166, 3.0%) and the oral therapy (n = 4/42, 9.5%) (P = 0.084). The efficacy of the ceftriaxone-based regimens was found to be better (n = 6/166 [3.6%] versus n = 6/42 [14.3%]; P = 0.017) when a composite negative outcome (CNO; relapse plus therapeutic failure) was considered. Accordingly, CNO was greatest in P2 (14.3%, n = 6/42) compared to P1 (2.6%, n = 3/117) and P3 (6.1%, n = 3/49) (P = 0.020). Seemingly, ceftriaxone-based regimens are more successful and require shorter therapy than the oral treatment protocol.

Evaluation of inflammatory and hematological parameters in patients diagnosed with COVID-19.

INTRODUCTION: This study aims to research the effects of hematological and inflammatory parameters on the prognosis of COVID-19 disease and hospitalization duration. METHODOLOGY: One hundred and eighty-six patients with COVID-19 and a control group consisting of 187 healthy individuals were included in the study. Hematological variables and inflammatory parameters of the patients were recorded on the first and the fifth days of hospitalization. RESULTS: White blood cell count, lymphocyte count, and platelet count were statistically lower, and mean platelet volume (MPV), neutrophil to lymphocyte ratio (NLR), and platelet to lymphocyte ratio (PLR) levels were higher in the patient group compared to the control group. It was observed that the neutrophil count and MPV level were lower, and the platelet count and ferritin level were statistically higher on the fifth day of follow-up compared to the admission day. In contrast, there was a significantly positive correlation between the duration of hospitalization and the fifth day D-dimer (r = 0.546, p < 0.001) and ferritin (r = 0.568, p < 0.001); in addition, there was a negative correlation between the duration of hospitalization and admission day lymphocyte count and the fifth-day lymphocyte count. CONCLUSIONS: Increased levels of ferritin and D-dimer, and decreased count of lymphocytes are among the important factors affecting the duration of hospitalization for COVID-19 patients. Furthermore, we think that neutrophil count and MPV levels are low, and platelet count and ferritin levels are high during the disease. Therefore, these parameters can be used as prognostic indicators of the disease.

Antiviral kinetics of tenofovir alafenamide and tenofovir disoproxil fumarate over 24 weeks in women of childbearing potential with chronic HBV.

BACKGROUND/PURPOSE: Use of tenofovir disoproxil fumarate (TDF) improves patient outcomes in preventing mother-to-child transmission (pMTCT) of the hepatitis B virus (HBV) in mothers with chronic HBV and high viral loads. Given the lack of data for tenofovir alafenamide (TAF) in pMTCT, rates of early viral suppression with TAF and TDF were evaluated in women of childbearing potential (WOCBP) participating in 2 randomized, double-blind, Phase 3 studies in chronic HBV. METHODS: In a patient subset meeting WOCBP criteria and with baseline HBV DNA >200,000 IU/mL, rates of viral suppression with TAF or TDF in achieving the target of HBV DNA <200,000 IU/mL at weeks 12 and 24 were assessed. Multivariate logistic regression was used to identify factors predictive of failure to suppress HBV DNA to the target level. RESULTS: In 275 of 1298 (21%) patients meeting WOCBP criteria with high viral load, 93% and 96% had HBV DNA <200,000 IU/mL at weeks 12 and 24, respectively. Results for TAF (n = 194) vs TDF (n = 81) treatment were similar at weeks 12 and 24 (94% vs. 90% and 97% vs. 93%), respectively. High baseline HBV DNA level, genotype D infection, and prior interferon (week 24 only) were predictive of failure to achieve the target level. Both treatments were well tolerated with TAF showing less impact on renal and bone parameters. CONCLUSIONS: In WOCBP with high VL, no differences were found between TAF and TDF in reducing HBV DNA to levels associated with lower transmission risk. These data support ongoing studies of TAF for pMTCT.

Real-World Data from Turkey: Is Sofosbuvir/Ledipasvir With or Without Ribavirin Treatment for Chronic Hepatitis C Really Effective?

BACKGROUND: In this study, we aimed to investigate the efficacy and safety of sofosbuvir-based therapies in the treatment of chronic hepatitis C in real-world clinical practice. METHODS: Data from patients with chronic hepatitis C treated with SOF/LDV ± RBV or SOF/RBV in 31 centers across Turkey between April 1, 2017, and August 31, 2018, were recorded in a nationwide database among infectious disease specialists. Demographics, clinical, and virological outcomes were analyzed. RESULTS: A total of 552 patients were included in the study. The mean age of the patients was 51.28 ± 14.2, and 293 (55.8%) were female. The majority had HCV genotype 1b infection (65%), 75.04% of the patients underwent treatment, and non-cirrhosis was present at baseline in 381 patients (72.6%). SOF/LDV ± RBV treatment was given to 477 patients and 48 patients received SOF/RBV according to HCV genotype. The total SVR12 rate was 99% in all patients. Five patients experienced disease relapse during the study and all of them were genotype 2. In patients infected with HCV GT2, SVR12 was 77.3%. SVR was 100% in all patients infected with other HCV genotypes. All treatments were well tolerated by patients without causing severe adverse events. Side effects and side effects-associated treatment discontinuation rates were 28.2% and 0.4%, respectively. Weakness (13.7%) was the common side effect. CONCLUSION: The present real-world data of 525 patients with HCV genotypes 1, 1a, 1b, 3, 4, and 5 who underwent SOF/LDV ± RBV treatment in Turkey demonstrated a high efficacy and safety profile. HCV GT2 patients should be treated with more efficacious treatment.

Prognostic value of Golgi P 73 and Beta 2-microglobulin in patients with Viral Hepatitis B.

Previous studies detected higher Golgi protein 73 levels in the serum of patients with chronic liver disease. The Beta-2 microglobulin levels were also observed to be higher in patients with chronic hepatitis B infection compared to the inactive carriers and the protein plays an important role in the response to viral infections. The aim of the present study was to assess the liver fibrosis through non-invasive methods in chronic hepatitis B patients. Three groups were included in the study. The first group comprised of the patients who were admitted to the Infectious Diseases and Clinical Microbiology clinic to undergo a liver biopsy, while the second group included the patients who were admitted inactive hepatitis B carriers. The third group comprised the healthy controls. The Golgi p-73 and Beta-2 microglobulin levels in the plasma were determined using the ELISA method. Beta-2 microglobulin level was highest in the patients group and the difference was statistically significant. No significant difference was observed between the carriers group and the group of healthy controls. The Golgi P-73 values were significantly higher in the patients group in comparison to both other groups. However, the mean Golgi p-73 value was also significantly higher in the carrier group compared to the control group. In patients who are followed up with the diagnosis of chronic hepatitis B and who have undergone biopsies as candidates for treatment, the Beta-2 microglobulin and Golgi p-73 values may be important markers since they indicate the extent of the liver damage.

Real-world efficacy, safety, and clinical outcomes of ombitasvir/paritaprevir/ritonavir ± dasabuvir ± ribavirin combination therapy in patients with hepatitis C virus genotype 1 or 4 infection: The Turkey experience experience.

BACKGROUND/AIMS: mbitasvir/paritaprevir/ritonavir (OMV/PTV/r) ± dasabuvir (DSV) ± ribavirin (RBV) combination has demonstrated excellent rates of sustained virologic response (SVR) and a very good safety profile in patients with the chronic hepatitis C virus (HCV) genotype 1 or 4 infections. We aimed to investigate the effectiveness and safety of OMV/PTV/r ± DSV ± RBV combination regimen in a real-world clinical practice. MATERIALS AND METHODS: Data from HCV genotype 1 and 4 patients treated with OMV/PTV/r ± DSV ± RBV (n=862) in 34 centers across Turkey between April 1, 2017 and August 31, 2018 were recorded in a large national database. Demographic, clinical, and virologic data were analyzed. RESULTS: The mean age of the patients was 55.63, and 430 patients (49.9%) were male. The majority had HCV genotype 1b infection (77.3%), and 66.2% were treatment-naïve. Non-cirrhosis was present at baseline in 789 patients (91.5%). SVR12 rate was 99.1% in all patients. Seven patients had virologic failure. No significant differences were observed in SVR12 according to HCV genotypes. HCV RNA was undetectable at treatment week 4 in 90.9%, at treatment week 8 in 98.5%, and at the end of treatment (EOT) in 98.9%. SVR12 ratio was significantly higher in the non-cirrhotic patients compared to that in the compensated cirrhotic patients. Rates of adverse events (AEs) in the patients was 59.7%. CONCLUSION: The present real-life data of Turkey for the OBV/PTV/r ± DSV ± RBV treatment of patients with HCV genotype 1b, 1a, or 4 infection from 862 patients demonstrated high efficacy and a safety profile.

Molecular Identification of HIV-1 in the Presence of Hepatitis B Virus and Hepatitis C Virus Co-infections

Background: Because of their similar modes of transmission, the simultaneous infection of viral hepatitis and human immunodeficiency virus are increasingly seen as a big problem related to human health. Aims: To determine the drug mutations in hepatitis B virus and/or hepatitis C virus co-infected human immunodeficiency virus-1 patients in Turkey. Study Design: Retrospective cross-sectional study. Methods: The present study was conducted between 2010 and 2017. HBsAg, anti-hepatitis C virus, and anti-human immunodeficiency virus were tested with ELISA. All anti-human immunodeficiency virus positive results by ELISA were verified for anti-human immunodeficiency virus positivity by a Western blot test, and Anti-human immunodeficiency virus positive patients with HBsAg and/or anti-hepatitis C virus positivity were included in the study. Subtyping and genotypic resistance analyses were performed by population sequencing of the viral protease and reverse transcriptase regions of the human immunodeficiency virus-1 pol gene. Results: We detected 3896 human immunodeficiency virus-1 positive patients whose sera were sent from numerous hospitals across the country to our polymerase chain reaction unit for detection of drug resistance mutations and whose molecular laboratory tests were completed. Viral hepatitis co-infections were detected in 4.3% (n=170) of patients. Hepatitis B virus and hepatitis C virus co-infection were observed in 3.2% and 0.5% of all human immunodeficiency virus-1 infected patients, respectively. The major human immunodeficiency virus-1 subtype detected was group M, subtype B (62.9%). However, 13.5% of drug resistance mutation motifs were found in human immunodeficiency virus-1 genomes of patients included in the study. Conclusion: Due to similar transmission routes, HIV1 patients are at risk of hepatitis B and C virus co-infection. However, antiretroviral drug resistance mutation model is similar to patients with hepatitis negative.

Are sinus-track cultures reliable for identifying the causative agent in chronic osteomyelitis?

PURPOSE: The infection of bone that contains bone marrow called osteomyelitis, and is caused by different microorganisms. In this study, we aimed to determine the diagnostic value and accuracy of cultures of material from a sinus track compared with those of cultures of bone specimens that have been controversial. MATERIALS AND METHOD: Prospective study was conducted at Hospital University of Dicle, a 1,090-bed university-based hospital located in Diyarbakir, Turkey. Between May 2005 and September 2006, sinus-track cultures were compared with those of bone cultures from 43 patients with chronic osteomyelitis. RESULTS: The patients' mean age was 30.6 +/- 3.6 years, and 29 (67%) male and 14 (33%) female. Organisms isolated from bone cultures were Staphylococcus 69% (29/42), Escherichia coli 9.5% (4/42), Pseudomonas aeruginosa 9.5% (4/42), Proteus mirabilis 7% (3/42), respectively. Cultures of sinus track and bone specimens gave identical results in 38% of patients. CONCLUSION: The value of bone culture in the therapy of osteomyelitis must be emphasized; it is the only reliable means of determining the responsible agent, up on which the antibiotic therapy is based. The correlation between sinus track and bone cultures was 38%, i.e., failure in the treatment for 6 patients out of 10.