Therapeutic Efficacy of Entecavir and Tenofovir among the Affectees from War against Terror in the Tribal Areas of Pakistan

BackgroundHepatitis B infection is a worldwide health concern infecting more than 400 million people worldwide. Besides the active immunization program of WHO, the role of antivirals for treating the chronic infection is inevitable. The tribal belt of Pakistan is the most affected part in war against terror. In addition to lack of basic facilities and resources, this part of country has also been neglected for various health related studies. In this study we report the efficacy of the commonly used antivirals; Entecavir (ETV) and Tenofovir Disoproxil Fumarate (TDF).MethodsA total of 2875 HBV infected patients (Male = 1500 and Female = 1375) of different age groups who were receiving either ETV as monotherapy or ETV plus TDF were followed up for 6 and 12 months. Viral DNA was extracted from serum followed by amplification and detection with MyGo Real-Time thermocycler and Gene Proof PCR kit. Response towards antivirals was analyzed statistically with Pearson’s Chi Square test. ResultsComparable response (p=0.171) was observed among the HBV patients towards both six (27%) and twelve month antiviral therapy (36%). Duration of antiviral therapy improved the rate of response in male and patients of old age (p=0.001 & <0.001 respectively). However, female were found relatively more responsive than males towards both six and twelve antiviral therapy (p=0.001 & 0.003 respectively). Furthermore, ETV plus TDF combination proved little more effective for twelve months (p=0.035). Patients of Khyber (p=0.198) and Kurrum (p=0.440) regions are equally responsive towards 6 and 12 month treatment. Compared to ETV monotherapy, ETV plus TDF improved response among the male, patients above 40 years and patients from different tribal region (Bajaur, Kurrum, Malakand and Mohmand). ConclusionOur findings demonstrate that the ETV monotherapy and ETV plus TDF combination therapy are not effective for the HBV infection because both do not achieve SVR rate even in 50% of patients following six and twelve-month follow-up. Therefore, there is a need of much more effective antiviral drugs to treat HBV infection in the study area.

Deoxycholic acid liganded HBs contributes to HBV maturation

Understanding the underlying mechanism of HBV maturation and subviral particle production is critical to control HBV infection and develop new antiviral strategies. Here, we demonstrate that deoxycholic acid (DCA) plays a central role in HBV production. HBV infection increased DCA levels, whereas elimination of DCA-producing microbiome decreased HBV viral load. DCA can bind to HBs antigen via LXXLL motif at TM1 and TM2 region to regulate HBs-HBc interaction and the production of mature HBV. Plasma DCA levels from patients undergoing antiviral therapy were significantly higher in those with positive HBV viral load. These results suggest that intestinal DCA-producing microbiome can affect the efficiency of antiviral therapy and provide a potential novel strategy for HBV antiviral therapy.

Clinical and epidemiological characteristics and effectiveness of antiviral therapy for COVID-19 in children: The experience of the first year of the pandemic

Background. The use of antiviral agents can shorten the duration of the viral infection. The aim: to study the clinical and epidemiological features and the effectiveness of antiviral therapy for new coronavirus infection (COVID-19) in outpatient children.Materials and methods. From April 2020 to March 2021, 9334 outpatient children aged from 0 months to 17 years were randomly tested for new coronavirus infection. SARS-CoV-2 RNA was detected in oropharyngeal and nasal material by PCR. Patients with confirmed new coronavirus infection were prescribed interferon-alpha (IFN-α) intranasally, antiviral agents of systemic action. The control group consisted of children with COVID-19 who did not receive treatment.Results. When examining clinically healthy contact children, SARS-CoV-2 RNA was detected in 7.4 % of cases. In the structure of ARI, the specific weight of COVID-19 was 12.3 % with the peak incidence in April-May (up to 22.8 %) and NovemberDecember (up to 30.0 %). In half of the cases, children became infected in the family, and usually adults were the index patient. In 47.7 % of cases, an asymptomatic form of COVID-19 was registered without significant differences in patients of different ages. In one third of children with concomitant pathology, the disease was asymptomatic, in half it was mild, in other cases moderate severity was diagnosed. The clinical picture of COVID-19 did not differ from other ARIs. Anosmia (9.4 %) in half of the cases was combined with ageusia (4.4 %) and was significantly more common in boys. The duration of clinical manifestations in children of the control group and those who received antiviral therapy did not statistically significantly differ in mild and severity of the disease. Also, various antiviral therapy options did not significantly affect the duration of SARS-CoV-2 detection in children with various forms of COVID-19.Conclusion. In the first year of the pandemic, the novel coronavirus infection did not dominate the pattern of respiratory diseases in outpatient children. Further research is required to develop pediatric guidelines for the treatment of COVID-19 at the outpatient stage.

Incidence And Predictors of Relapse After Stopping Antiviral Therapy In Pediatric Chronic Hepatitis B

Objective: The objective was to evaluate the incidence of relapse after stopping antiviral therapy and to identify the predictors of relapse. Methods: All HBsAg positive children with who had been on antivirals for at least 2 years with undetectable HBV-DNA and normal alanine-aminotransferase (ALT) on three consecutive occasions over last 12 months were included. Antivirals were stopped if liver biopsy showed histological activity index <5 and fibrosis (metavir) <3. Children were monitored for virological relapse (elevation of HBV-DNA >2000 IU/mL) and biochemical relapse (ALT levels >2 × upper limit of normal (ULN)). Those having biochemical relapse were started on pegylated interferon alpha-2b based sequential therapy. Results: Antivirals were stopped in 31 HBsAg positive children. Virological and biochemical relapse was seen in 12 (38.7%) and 5 (16.1%) children within 12 months of stopping antiviral treatment. Majority of virological relapse occurred within a month and biochemical relapses within 6 months of stopping therapy. HBeAg positive status at the time of stopping antiviral therapy (HR: 7.206, p =0.005) and longer time taken for HBV-DNA to become undetectable while on antivirals (HR: 1.030, p=0.037) were found to be the 2 independent predictors of relapse after stopping antiviral treatment. Conclusion: Discontinuation of antiviral treatment in children with CHB resulted in relapse in one third of the patients. Relapse was more common in those with HBeAg positivity at the time of stopping therapy and in those with longer time taken for HBV-DNA to become undetectable on antivirals.

The experience of the Moscow City Center for AIDS Prevention and Treatment of using glecaprevir/pibrentasvir in patients with HIV/HCV coinfection

The aim of the study is to analyze the experience of the Moscow Center for HIV/AIDS Prevention and Treatment on antiviral therapy of chronic hepatitis C in patients with HIV/ HCV coinfection in real-world evidence (RWE).Methods. The data from the outpatient cards of 12 adults and 53 children with HIV/HCV in the Moscow Center for HIV/AIDS Prevention and Treatment were analyzed for the period from 2020 to October 2021. In addition to standard laboratory tests, the viral load of HIV RNA, HCV RNA was examined in all patients, the HCV genotype was determined, the degree of liver fibrosis was assessed by liver fibroelastometry.Results: Among adult patients 10 (83,4%) were infected with HCV Gt 3, while 2 patients (16,6%) had Gt 1a/3. 5 (41,7%) patients were treatment-naïve and 7 (58,3%) had previously received sofosbuvir and daclatasvir. All 12 adult patients received glecaprevir/pibrentasvir for 8-16 weeks, depending on the treatment experience. 3 (25%) patients with HCV Gt 3 previously treated with DAAs received triple combination of glecaprevir/pibrentasvir, sofosbuvir and ribavirin for 12 weeks. As a result, 100% (12/12) of patients treated with glecaprevir/pibrentasvir achieved SVR12, no adverse events or cases of intolerance were identified.In the general group of adolescents with HCV/HIV coinfection (n = 53), the distribution by HCV genotypes was as follows: Gt 1 – 26 (49%), Gt 3 – 27 (51%). 15 (28,3%) adolescents received interferon-2a (SVR – 40% (6/15)), 9 adolescents received Peg-interferon-2a (SVR – 33% (3/9)) and 16 adolescents received glecaprevir/pibrentasvir. The mean duration of HIV/HCV coinfection in 16 adolescents receiving glecaprevir/pibrentasvir was 12,5 (1-17) years. Of these, 11 (68,3%) were infected with HCV Gt 1 and 5 (31,7%) with HCV Gt 3. 11 patients (68,3%) had prior treatment history with interferon and peginterferon regimens. The distribution of fibrosis stages was as follows: F0 – 56,3% (9/16), F1 – 31,3% (5/16), F2 – 12,4% (2/16). All 16 adolescents received 8 weeks of glecaprevir/pibrentasvir. 100% of patients were aviremic after 4 weeks from the start of therapy. All patients achieved SVR12. No adverse events and/or intolerance of glecaprevir/ pibrentasvir were identified.Conclusion. This observation demonstrates the high efficacy and safety of treatment with direct-acting antiviral drugs in both adults and children with HIV/HCV coinfection. Diagnosis and treatment of chronic hepatitis C in patients of reproductive age with HIV/HCV coinfection before pregnancy will help to completely eliminate the risk of mother-to-child transmission of HCV. Timely, effective, and modern antiviral therapy of already infected adolescents with HCV will make it possible to take a step towards eliminating hepatitis C through microelimination in the described socially significant groups of patients