Lamivudine Therapy Research Articles

The Study of Efficacy and Safe of Lamivudine in Patients with Severe Acute Hepatitis B

Objectives: Lamivudin has been approved for the treatment of chronic hepatitis B but experience with lamivudin treatment for acute severe hepatitis B is still limited. Fulminant hepatitis develops in 1% of patients with acute hepatitis B. Severe acute hepatitis B in immunocompetent patients may progress to fulminant hepatitis and death. Aim: To evaluate the efficasy of lamivudine for the treatment of acute severe hepatitis B virus infection in imunocompetent adults in Clinic for infectious diseases Banja Luka. Patients and methods: In the period of 2006-2024 years, 12 immunocompetent patients (4 women, 8 men, age 24-77 years) with severe acute hepatitis B were treated with lamivudin. All 12 patients fulfil at least two of the criteria for severe acute hepatitis B infection: 1. hepatic encephalopathy; 2. total bilirubin 210 micromole per litre; and severe coagulopathy (international normalized ratio-INR was 4.5 ± 6.4 or prothrombin time-PT < 40%). All patients had evidence of severe hepatocyte lysis. Nine patients had rapid increase of total bilirubin and contemporary decrease of alanine aminotransferase level, which escalate risk of development of fulminant hepatitis B. All patients received lamivudin at a dose 100 mg per day. Results: Ten patients responded well to the treatment and their biochemical parameters improved rapidly. Within 1-6 months, the HBsAg was undetectable in 10 out of 12 investigated patients. Protective anti-HBs antibodies developed in 10 of them in 1-6 months. The corticosteroid therapy was short-term in 2 of 12 patients. Two patient developed fulminant hepatitis B and died after the lamivudine therapy was initiated. Lamivudine treatment was well tolerated in all patients. Conclusion: Lamivudin induces a prompt clinical, biochemical and serological response in immunocompetent patients with severe acute hepatitis B. Early treatment with lamivudine probably decreases the risk of progression to fulminant hepatitis in patients with severe acute hepatitis B.

Role of B Cells beyond Antibodies in HBV-Induced Oncogenesis: Fulminant Cancer in Common Variable Immunodeficiency-Clinical and Immunotransplant Implications with a Review of the Literature.

Although lymphoma is the most frequent malignancy in common variable immunodeficiency (CVID), solid tumors, especially affected by oncogenic viruses, are not considered. Furthermore, in vitro genetic studies and cell cultures are not adequate for immune system and HBV interaction. We adopted a previously introduced clinical model of host-virus interaction (i.e., infectious process in immunodeficiency) for analysis of B cells and the specific IgG role (an observational study of a CVID patient who received intravenous immunoglobulin (IVIG). Suddenly, the patient deteriorated and a positive results of for HBs and HBV-DNA (369 × 106 copies) were detected. Despite lamivudine therapy and IVIG escalation (from 0.3 to 0.4 g/kg), CT showed an 11 cm intrahepatic tumor (hepatocellular carcinoma). Anti-HBs were positive in time-lapse analysis (range 111-220 IU/mL). Replacement therapy intensification was complicated by an immune complex disease with renal failure. Fulminant HCC in CVID and the development of a tumor as the first sign is of interest. Unfortunately, treatment with hepatitis B immune globulins (HBIG) plays a major role in posttransplant maintenance therapy. Anti-HB substitution has not been proven to be effective, oncoprotective, nor safe. Therefore, immunosuppression in HBV-infected recipients should be carefully minimized, and patient selection more precise with the exclusion of HBV-positive donors. Our clinical model showed an HCC pathway with important humoral host factors, contrary to epidemiological/cohort studies highlighting risk factors only (e.g., chronic hepatitis). The lack of cell cooperation as well as B cell deficiency observed in CVID play a crucial role in high HBV replication, especially in carcinogenesis.

Efficacy of Lamivudine and Dolutegravir simplification therapy compared with triple therapy in Northeast Brazil (LAMDO Study)

Background: Modern antiretroviral therapy provides numerous effective and well-tolerated treatment options for individuals living with HIV. However, due to medication tolerability, toxicity, and cost optimization associated with the emergence of highly potent drugs, dual therapy has emerged as a new therapeutic alternative for patients with viral suppression. Observational studies worldwide are being conducted to assess the effectiveness of dual therapy in people living with HIV/AIDS. A real-world study is important to validate the findings obtained in controlled studies. Objective: Assess the effectiveness of dual therapy with lamivudine and dolutegravir compared to triple therapy in real-life settings. Methods: The study was conducted at São José Infectious Diseases Hospital, a tertiary referral hospital in the state of Ceará, northeast Brazil, for the treatment of PLWHA. Results: A total of 521 patients were taking double therapy with lamivudine plus dolutegravir and 450 patients were in triple therapy, mostly in the use of association with dolutegravir, were analyzed. Patients on dual therapy had a higher median age compared to those on triple therapy. A statistically significant higher viral suppression was observed in patients on dual therapy compared to triple therapy (p < 0,001). Viral suppression on dual therapy under 200 copies was 97.2%. There was a statistically significant higher percentage of patients with higher CD4/CD8 ratio using triple therapy compared to dual therapy. Conclusion: The current study suggests a higher effective response to dual therapy compared to triple therapy in PLWHA in the real-world, supporting therapy simplification as a sustainable option to maintain virological suppression in patients experiencing toxicity or comorbidities.

Preliminary study on the relationship between recurrence and quasispecies characteristics in P region of hepatitis B virus genome of chronic hepatitis B patients treated with lamivudine

Purpose: To investigate the characteristics of quasispecies in the P region of hepatitis B viral (HBV) DNA of chronic hepatitis B (CHB) patients treated with lamivudine (LAM), and its effect on HBV relapse after drug withdrawal in CHB patients who met drug cessation criteria.
 Methods: A total of 43 patients with chronic HBV infection, who had undergone LAM therapy, were enrolled in this study. Treatment was discontinued for patients who met therapeutic criteria set by relevant Asian-Pacific regions. Polymerase chain reaction (PCR) was used to amplify the genome in P region of serum rcDNA before treatment, cccDNA during drug cessation period, and serum rcDNA at relapse. Quasispecies cloning and sequencing were performed to identify variable sites in HBV P region.
 Results: Mutations in P region of baseline serum rcDNA were detected in 30 CHB patients, with N/H238T (14/30), L/F/Q/R267H (12/30), V278T (12/30), D134E/I (11/30), and T222A (9/30) having highest rates. In hepatocellular cccDNA P region during drug withdrawal, most detectable mutations were L/F/Q/R267H (25/43), V278T (18/43), N/H238T (15/43), D134E/I (14/43), and T222A (11/43). During relapse, the highest detectable mutation rates in serum rcDNA P region were N/H238T (12/19), L/F/Q/R267H (10/19), T222A (10/19), and V278T (8/19).
 Conclusion: High mutation rates of T222A and N/H238T in P region of HBV DNA increase the risk of relapse in patients. As a result, patients are susceptible to relapse after drug withdrawal.

Efficacy and Safety of a Simplified Lamivudine Plus Dolutegravir Dual Therapy in HIV-1-Infected Patients: A Multicenter Cohort Study in China.

Results from both clinical trials and real-world observational studies suggest that lamivudine plus dolutegravir (3TC + DTG) dual therapy has excellent virological efficacy and safety in HIV-1-infected patients. However, there is still no relevant study related to this dual therapy reported in China. In this multicenter, retrospective, observational study that included HIV-1-infected patients in China, baseline and follow-up data were collected to analyze the virological suppression rate, immune restoration, and adverse events during follow-up in HIV-1-infected patients who switched to the 3TC + DTG dual therapy. This study recruited 112 HIV-1-infected patients, including 101 men (90.2%), with a median age of 44.0 years (IQR: 33.00-57.75) and median CD4+ T-cell count of 432.13 cells/μL (IQR: 237.75-578.50). The overall virological suppression rate was 94.5% at the 24-week follow-up. However, the virological suppression rates of men who have sex with men patients and patients with CD4+ T-cell count of <350 cells/μL were higher than the baseline value (P < 0.05) at week 24. The results of Cox regression analysis showed that the baseline CD4+ T-cell count was an independent determinant of immune restoration in patients, and patients with baseline CD4+ T-cell count of 350-500 cells/μL outperformed patients with baseline CD4+ T-cell count of <350 cells/μL in immune restoration (hazard ratio: 4.469, 95% confidence interval: 1.801 to 11.091, P = 0.001). Adverse events were reported in 5 patients (incidence rate of 4.5%); among them, 3 patients developed neuropsychiatric symptoms. Results from the laboratory data analysis showed that patients with grade 1 and 2 adverse events had elevated levels of low-density lipoprotein cholesterol and total bilirubin. Furthermore, grade 3 and 4 adverse events were associated with the elevation of blood glucose level in 4 patients. Thus, the 3TC + DTG dual therapy displayed an excellent virological efficacy against HIV-1 infections and had an acceptable safety profile, with predominantly mild adverse events in HIV-1-infected patients in China.

Risk factors and prognostic significance of anemia in children with HIV infection on antiretroviral therapy.

To establish the incidence, risk factors and prognostic effect of anemia in children living with HIV (CLWH). Retrospective nested case-control study of patients 0-18 years in five centers in sub-Saharan Africa, 2004-2014. Incident cases of anemia were identified from electronic records and matched with CLWH without anemia. We calculated the incidence density of anemia and used conditional logistic regression to evaluate its association with risk factors, stratified by severity and type of anemia. We used a Cox proportional hazards model to evaluate the impact of anemia on survival. Two thousand, one hundred and thirty-seven children were sampled. The incidence density of anemia was 1 per 6.6 CLWH-years. Anemia was moderate in 31.8% and severe in 17.3% of anemia cases, which had 10-year mortality hazards of 3.4 and 4.5, respectively. Microcytic anemia (36% cases) was associated with 2.3-fold hazard of 10-year mortality, and with malnutrition and CD4 + suppression. Normocytic anemia (50.5% cases) was associated with 2.6-fold hazards of 10-year mortality, and with more severe malnutrition, CD4 + suppression, and WHO stage, but inversely associated with lamivudine and nevirapine therapy. Macrocytic anemia (13.5% cases) was neither associated with higher 10-year mortality nor with severe malnutrition or CD4 + suppression but was associated with WHO stage II/III and negatively associated with lamivudine therapy. This large multicountry study of CLWH found a high incidence density of anemia. Higher severity, normocytic and microcytic types of anemia were independently associated with long-term mortality. Laboratory studies are needed to decipher the mechanisms of anemia and how it impacts mortality in CLWH.

A CASE OF THYROTOXIC PERIODIC PARALYSIS AND MODERATE TO SE- VERE GRAVE’S OPHTHALMOPATHY REQUIRING INTRAVENOUS STEROID THERAPY WITH A COMORBIDITY OF CHRONIC HEPATITIS B INFECTION

Grave’s disease is an autoimmune thyroid disease with several characteristic symptoms and signs. Grave’s ophthalmopathy, an inflammatory disease in the orbital area, is the primary extrathyroid manifestation of Grave’s disease. About 5% of Grave’s ophthalmopathy patients have moderate to severe severity requiring high doses of systemic corticosteroid therapy. Grave’s disease also has a few complications, one of which is thyrotoxic periodic paralysis characterized by hypokalemia and muscle paralysis. Chronic hepatitis B virus infection has the potential to be co-incidence with other diseases (e.g., Grave’s ophthalmopathy). The need for a high dose of corticosteroid therapy in treating Grave’s ophthalmopathy is a risk of reactivation in hepatitis B-infected patients. This paper presented a Grave’s disease patient complicated with Grave’s ophthalmopathy who developed limb muscle weakness. The patient will receive high doses of corticosteroids and prophylactic lamivudine therapy to prevent hepatitis B virus reactivation.

Long-term follow-up of treatment-naïve HBeAg-negative patients with chronic hepatitis B.

We aimed to explore long-term results of oral antiviral agents in treatment-naïve "HBeAg negative chronic hepatitis B (CHB)" and determine the factors affecting the complete virological response. Patients with HBeAg-negative CHB who used oral antiviral agents for at least 3years were evaluated retrospectively. A total of 173 patients were recorded. The mean duration of treatment was 62.2 ± 28.9months. Complete virological responses (CVR) were 82.8% (n = 53/64) in tenofovir disoproxil fumarate (TDF), 84.4% (n = 49/58) in lamivudine (LAM), 83.9% (n = 26/31) in entecavir (ETV), 95% in telbivudine (LdT) (n = 19/20) (p = 0.290). Multivariate analysis revealed age ≤ 40 (p = 0.012, 95%CI = 1.38-13.76, OR = 4.36) and baseline HBV DNA value (p = 0.003, 95%CI = 1.23-2.63, OR = 1.78) as independent factors for CVR. Virological breakthrough was detected in 29 (50%) patients on LAM therapy, two (6.4%) patients on ETV therapy, and two (10%) patients on LdT therapy. Treatment was switched to another antiviral agent due to osteoporosis in four patients in the TDF group, muscle pain in nine patients in the LDT group, and headache in one patient in the ETV group. Hepatocelluler cancer was detected in five patients. HBsAg seroclearance developed in two patients. Anti-HBs seroconversion was not detected. CVR was achieved at similar rates with all four antiviral agents, while younger age (≤ 40) and low baseline viral load were the main factors for virological response. However, drug resistance and virological breakthrough in the LAM group and side effects in the LdT group were detected during the long-term follow-up. Moreover, HBsAg seroclearance was achieved at very low rates with oral antiviral agents.

A Case of Thyrotoxic Periodic Paralysis and Graves’ Ophthalmopathy Patient in Coincidence with Chronic Hepatitis B Infection

Graves' disease is an autoimmune thyroid disease with several characteristic symptoms and signs. Graves' ophthalmopathy, an inflammatory disease in the orbital area, is the main extrathyroid manifestation of Graves' disease. About 5% of Graves' ophthalmopathy patients have moderate to severe severity requiring high doses of systemic corticosteroid therapy. Graves' disease also has few complications, one of which is thyrotoxic periodic paralytic characterized by hypokalemia and muscle paralysis. Chronic hepatitis B virus infection has the potential to be co-incidence with other diseases (eg Graves ophthalmopathy). The need of high dose of corticosteroid therapy in treating Graves’ ophthalmopathy is a risk of reactivation in hepatitis B infection patient. This paper presented a Graves' disease patient complicated with Graves’ ophthalmopathy who developed limb muscle weakness. Patient will receive high doses of corticosteroids and prophylactic lamivudine therapy to prevent hepatitis B virus reactivation.

Relationship of Hearing Impairment in Patients with Lamivudine Therapy: A Systematic Review and Meta-analysis

Introduction: Lifelong Antiretroviral Therapy (ARVT) in patients with Human Immunodeficiency Virus (HIV) infection damages cochlea. Hearing Loss (HL) has been reported with lamivudine therapy in both HIV and/or Hepatitis B Virus (HBV) infections. Hence, the benefit of lamivudine therapy in individuals affected by these infections and risk of development of HL needs to be studied to make an adequate benefit-risk assessment. Aim: To evaluate the relationship of hearing impairment in patients treated with lamivudine and diagnosed with either HIV or HBV infection. Materials and Methods: The present study is a systematic review in which English-language publications that assessed HL in patients who are on lamivudine drug therapy were included. The types of studies included were: prospective studies, retrospective studies, case reports and case series. A comprehensive database search (PubMed, PubMed Central, Cochrane review, Google scholar and Embase) was conducted to identify the relevant literature published on HL and were searched for keywords related to lamivudine and HL- ‘lamivudine and hearing loss’, ‘lamivudine and deafness’, ‘lamivudine and hypoacusis’, ‘lamivudine and hearing impairment’ and ’lamivudine and ototoxicity’ for searching the data. The publications were independently reviewed and assessed for study quality and the data (title, author, year of publication, study design, study setting, population characteristics) extraction was done. Results: Out of 1,778 publications found at the initial stage, nine were included in the systematic review and quantitative metaanalysis. The majority (4/9) were cross-sectional studies. The prevalence of hearing impairment defined as per the protocol was 41% (total population 1,548). The I2 statistic was used to test statistical heterogeneity, with values of &gt;50% representing important heterogeneity, then a random-effects model was used to perform the meta-analysis. A subgroup analysis was performed for the age group ≤18 years and &gt;18 years. All analyses were conducted using the R software version 4.1.0. It was found that most of the studies (8/9) suffered moderateserious overall risk across all the domains of ROBINS-1 tool. Conclusion: This study showed a positive association of HL with lamivudine in patients with HIV infection.

Effects of dyslipidemia on E antigen seroconversion of patients with chronic hepatitis B treated by nucleoside (acid) analogs

BackgroundThe prevalence of dyslipidemia in China is increasing annually. Current studies suggest that dyslipidemia affects the antiviral efficacy of hepatitis C virus (HCV) therapies, while recent studies suggest that serum lipids influence the response rates of chronic hepatitis B (CHB) patients receiving PEGylated interferon-alpha (Peg IFN-α) treatment. However, the role of dyslipidemia in the efficacy of nucleoside (acid) analogues (NAs) in CHB patients remains unclear.MethodsFrom January 2010 to December 2013, data from 179 treatment-naive patients with CHB who were hepatitis B e antigen (HBeAg)-positive and had visited the first affiliated hospital of Wenzhou Medical University were assessed. Of these patients, 68 were assigned to the dyslipidemia group (diagnosed with CHB complicated with dyslipidemia) and 111 to the normolipidemic group. The following 3 treatment strategies were performed for all CHB patients over a 5-year period: lamivudine (LAM) plus adefovir dipivoxil (ADV) combination therapy, telbivudine (LdT) monotherapy, and entecavir (ETV) monotherapy. Serum assessments, blood biochemistry, HBV serological markers, HBV DNA before treatment and HBeAg serological conversion and virological responses at different timepoints after treatment were compared between the two groups. Measurement data were compared by τ tests and enumeration data by χ2 tests. Correlation analysis was performed using binary logistic regression analysis.ResultsThe rates of HBeAg seroconversion in the dyslipidemia group at years 1, 2, 3, and 4 were 10.3, 13.2, 17.6, and 22.1%, respectively, which were not significantly lower than those of the normolipidemic group (11.7, 16.2, 18.0 and 33.3%; χ2 = 0.085, 0.293, 0.004, and 2.601, respectively; Ρ > 0.05). However, the rates of HBeAg seroconversion in the dyslipidemia group were significantly lower than those in the normolipidemic group at year 5 (27.9% vs. 43.2%, χ2 = 4.216, Ρ < 0.05). Univariate logistic regression analysis revealed significant differences in group, gender, PTA, ALT, AST, CR, and LDL-C between groups with and without seroconversion. Multivariate regression analysis demonstrated that dyslipidemia (OR = 1.993, Ρ = 0.038) and male gender (OR = 2.317, Ρ = 0.029) were risk factors associated with HBeAg seroconversion.ConclusionsDuring antiviral therapy, dyslipidemia affects HBeAg seroconversion in CHB patients treated with NAs, but does not affect the virological response.

The Management of Hepatitis B Flare in Pregnancy

Background: Hepatitis B infection during pregnancy is still a unique problem for the mother and her fetus. These include the effects of hepatitis B on maternal and fetal health, the effects of pregnancy on hepatitis B infection in pregnancy, treatment of hepatitis B during pregnancy and prevention of mother-to-child transmission. Case description: A young woman was referred for jaundice in pregnancy. Physical examination revealed icteric sclera in both eyes. Laboratory tests show increased liver function as well as bilirubin. for testing for hepatitis B reactive. The patient received lamivudine therapy and cesarean section therapy. Conclusion: Management and treatment of chronic hepatitis B is difficult because of the variable course of the disease. It is even more complex in pregnant patients. Joint decision-making between physicians and female patients regarding the timing of initiation of antiviral therapy is critical to improving outcomes. Optimal initiation of antiviral therapy in the general population depends on the histologic degree of inflammation and fibrosis. We now know that post-partum HBIG and vaccination for infants born to chronically infected mothers can be ineffective in preventing MTCT to regulate increased maternal HBV viremia.

Inflammation Pharmacological Reaction and YMDD Mutational Patterns in Lamivudine Therapeutics Hepatitis B Virus.

Background/Aims: Emergence of tyrosine-methionine-aspartate-aspartate (YMDD) motif in reverse transcriptase is a serious problem in chronic hepatitis B(CHB) patients after Lamivudine (LAM) therapy. However, the relationship between inflammation pharmacological reaction and YMDD mutational patterns of CHB has not been well-characterized. The aim of this study was to investigate the inflammation pharmacological reaction and different YMDD mutants patterns of CHB patients. Methods: We investigated the inflammation pharmacological reaction and YMDD mutational patterns through biochemical, serological and virological detection among 83 CHB patients, including 25 YMDD mutants, 25 under detection, and 33 control patients without YMDD mutants. Results: Prevalence of YMDD mutation patterns is different. Among 25 YMDD mutants patients, YIDD was the dominant mutation (72%), followed YVDD (16%) and the hybrid YIDD + YVDD (12%). The time course during the YMDD mutations was also different. 52.4% patients developed the mutation less than 12 months after the LAM therapy. Serum hepatitis B virus (HBV) DNA level in patients with YMDD mutants were significantly higher than that in control and negative groups. Serum HbsAg and HbeAg in patients with YMDD mutants were also higher than those in control and negative groups, despite no significant difference was found forserum HbeAb. ALT and AST levels were also significantly higher in mutants group. Conclusions: Illuminating inflammation pharmacological reaction and YMDD mutational patterns of CHB during pathological process may have implications for future therapy in YMDD mutation patients. This may have impact on the choice of treatment strategies for lamivudine-resistant HBV.

Real-World Experience of Telbivudine and Lamivudine as Antiviral Prophylaxis for Chemotherapy-Related Hepatitis B Reactivation

Background: There is currently no data regarding the efficacy of prophylactic telbivudine in hepatitis B patients undergoing chemotherapy. This study aims to describe the results of preemptive telbivudine and lamivudine to prevent chemotherapy-related HBV reactivation.Methods: The medical records of all patients with HBsAg positive or HBs-Ag negative, anti-HBc positive, who were referred to the hepatology clinic between May 2014 and December 2016, were retrospectively reviewed. As this is a descriptive study, no statistical analysis was done.Results: A total of 52 patients with prophylactic telbivudine or lamivudine therapy were included, with 26 patients in each group. Rituximab-based treatment was given in nine and five patients in the telbivudine and lamivudine group, respectively. The number of patients who completed antiviral treatment up to six months after chemotherapy was 17 patients in each group. There was less incidence of HBV reactivation in the telbivudine group (2 of 17 patients, 11.8%) than in the lamivudine group (7 of 17 patients, 41.2%). Delayed reactivation was noticed in 1 of 2 patients in the telbivudine group and 3 of 7 patients in the lamivudine group. The median log10[HBV DNA] at reactivation was 4.52 (1.70 – 8.35) IU/mL. Severe hepatitis was observed in two patients in the lamivudine group and one patient in the telbivudine group. Of 34 patients who completed antiviral treatment, two patients died due to primary cancer. No interruption of chemotherapy or mortality due to hepatitis was noticed in both groups.Conclusions: Preemptive telbivudine or lamivudine in HBsAg positive or HBsAg negative, anti-HBc positive patients seems to be a good treatment option.

Prevalence of Hematological Abnormalities and Factors Associated Among HIVInfected Children Receiving Care at Kilimanjaro Christian Medical Centre

Background In HIV infected children, any of the cell lineages can be depressed during disease progression. Hematological complications such as anemia, neutropenia and thrombocytopenia were among clinical problem frequently reported in early years of AIDS. This study aimed to determine the magnitude of hematological abnormalities and factors associated with HIV infected children. Methods A cross-sectional analytical hospital based study was done from Sept 2016 to May 2017, and 201 HIV-infected children, below 14 years attending ART clinic during the study period were included. Social and nutrition history, ARV drugs used, clinical staging and anthropometric measurements were recorded. Blood samples for full blood count and HIV viral load were taken and analyzed by Mindray BC 5380 and Roche COBAS respectively. Data analysis was done using STATA where descriptive statistics for categorical variables were summarized using frequency and percentage. Odds Ratio (OR) with its 95% CI was used to measure the association between dependent variables and independent variables by using logistic regression. Results The median age of the participants was 9 years. Most of them 44.78% were on zidovudine, lamivudine and Niverapine regimen combination therapy. Prevalence of anemia, neutropenia and thrombocytopenia was found to be 42 (20.9%), 41 (20.4%), 4 (2%), respectively. Children under five years (OR 2.36, 95 % CI, 1.06-5.27) had higher viral load &gt;1,000 copies /mil, (OR 2.02, 95% CI, 1.01-4.07), those taking co-trimoxazole (OR 2.67, 95% CI, 1.31-5.46), those who had history of TB disease (OR 2.09, 95% CI, 0.92-4.75), and those with less than one year on ART (OR 3.14, 95 % CI, 1.02-9.63) were associated with anemia in bivariate analysis. However, in multivariate analysis for anemia, no factor remained significant. Having history of TB had higher odds of developing neutropenia (OR 2.18, 95% CI, 0.96-4.95) although it was not significant. Conclusion The prevalence of anemia and neutropenia in children is still high despite being on ARVs. Under-fives, taking co-trimoxazole, having higher viral load, TB disease history and being on ART for less than one year were are risks of developing anemia. Regular monitoring of hematological abnormality may help identify problems early and appropriate measures taken to prevent the effect of these abnormalities.

Association of hearing loss in the patients with treated with lamivudine: a systematic review protocol

&lt;p class="abstract"&gt;&lt;strong&gt;Background:&lt;/strong&gt; Hearing loss has been reported with lamivudine therapy. The World Health Organization (WHO) international database of suspected adverse drug reactions (Vigibase) prioritised clinical review of lamivudine and hearing loss in 2015. This manuscript provides the details of research protocol for a systematic review of association of lamivudine with hearing loss.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Methods: &lt;/strong&gt;English-language publications that assess hearing loss within patients who are receiving lamivudine therapy will be included. All study types like clinical trial designs, case-control study, cohort study, retrospective study, case-series or a case report will be included. Preclinical studies, studies enrolling patients with known differential diagnosis such as presbycusis etc will be excluded. Electronic databases (PubMed, Cochrane reviews, Embase and Google scholar), international clinical trials registry, clinicaltrials.gov and pharmaceutical company clinical study registries will be searched for key words related to lamivudine and hearing loss. After a thorough electronic/manual search of manuscript they will undergo a screening process and selected articles will be assessed for risk of bias using online ROBINS-I tool. We will explore outcomes as an observational systematic review.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Conclusions:&lt;/strong&gt; This review will provide detailed benefit-risk analysis of lamivudine with respect to hearing loss in patients with chronic conditions such as Human immunodeficiency virus (HIV) and Hepatitis B virus (HBV) infection.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Trial Registration:&lt;/strong&gt; PROSPERO registration number is CRD42018112205.0.001.&lt;/p&gt;

Hepatitis B virus X gene mutants emerge during antiviral therapy and increase cccDNA levels to compensate for replication suppression.

Hepatitis B virus (HBV) X gene (HBx) mutants can develop during the natural course of chronic HBV infection. However, little is known about whether the emergence of HBx mutants during long-term antiviral therapy is an adaptation of HBV to antiviral stress. This study was to identify HBx mutants that emerged in patients experiencing Lamivudine resistance or suboptimal treatment. Forty-six Lamivudine-resistant patients and 46 patients with suboptimal treatment responses to Entecavir were enrolled in this study. HBx mutants were identified by sequence analysis and their roles in the HBV replication cycle were characterized. We show that deletion/truncation/insertion mutations were only detected in the Lamivudine resistance group, while synonymous mutations were found in both groups. Follow-up analyses revealed that five patients in the Lamivudine group developed hepatocellular carcinoma, while patients in the Entecavir group did not. These mutants were characterized by a significant decrease in transactivation of the pre-S1 promoter, and varying effects on transactivation of the X promoter. Co-transfection of HBx-mutant plasmid and HBV replication-competent clone into HepG2 cells resulted in increased nuclear-to-cytoplamic HBV core antigen, HBV-DNA ratios, and nuclear covalently closed circular DNA (cccDNA). Antiviral drug sensitivity assays revealed that these mutants exhibited a compensatory effect to counteract antiviral drug suppression, resulting in elevated secretory HBV-DNA levels. Our study demonstrates that HBx mutants can emerge during Lamivudine or Entecavir therapy. These mutants exhibit altered transactivation of the HBV pre-S1 and X promoters, leading to increased cccDNA levels to compensate for replication suppression.

SAT447 - All-cause mortality and liver-related death following entecavir, tenofovir disoproxil fumarate or lamivudine therapy among treatment-naive chronic hepatitis B patients in British Columbia, Canada

SAT447 - All-cause mortality and liver-related death following entecavir, tenofovir disoproxil fumarate or lamivudine therapy among treatment-naive chronic hepatitis B patients in British Columbia, Canada

Nutritional dietary supplementation of d-ribose-l-cysteine ameliorates altered sperm parameters, hormone profile and testicular histomorphology in highly active antiretroviral therapy induced toxicity in adult male Wistar rat

BackgroundHighly Active Antiretroviral Therapy (HAART) in associated with several health conditions including testicular toxicity. This study investigated the nutritional importance of d-Ribose-l-Cysteine (DRLC) supplement in HAART induced testicular toxicity in adult male wistar rat. Materials and methodsThirty two (32) adult male Wistar rats (120 g–150 g) were divided into 4 groups (n = 8). Group A received normal saline as placebo; Group B received 2.3 mg/mL of HAART only (Lamivudine, Zidovudine and Nevirapine combination therapy); Group C received 2.3 mg/mL of HAART and 100 mg/kg BW of DRLC (low dose) and Group D received 2.3 mg/mL of HAART and 300 mg/kg BW of DRLC (high dose). All administrations were done through oral gavage for 42 days after which serum was obtained for analysis; sperm collected from the caudal epididymis was analyzed, and testis removed for antioxidant assay and histomorphology. ResultsThe results showed significant alterations in sperm parameters, oxidative markers, hormone profiles and defective testicular morphology in HAART only group when compared to the control. However, significant improvements were noticed after DRLC administration with restored sperm characteristics, increased antioxidant levels, restored hormonal assessments and preserved testicular structures. ConclusionNutritional attributes of DRLC attenuates HAART induced testicular toxicity through preservation of testicular function, morphology and semen characterization.

Entecavir add-on Peg-interferon therapy plays a positive role in reversing hepatic fibrosis in treatment-naïve chronic hepatitis B patients: a prospective and randomized controlled trial.

BackgroundThe efficacy of entecavir (ETV) add-on peg-interferon therapy compared with ETV monotherapy in treatment-naïve hepatitis B virus (HBV) patients remains controversial. We investigated whether adding peg-interferon to ongoing ETV treatment leads to a better curative effect or not.MethodsAll patients have been recruited between August 2013 and January 2015 from the Shanghai Public Health Clinical Center and Zhongshan Hospital (China). Eligible HBV patients (n = 144) were randomly divided (1:1) to receive either ETV monotherapy (n = 70) or peg-interferon add-on therapy from week 26 to 52 (n = 74). Patients were followed-up for at least 2 years. Indexes including hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) seroconversion rate, sustained virologic response, transient elastography value, and histological scores were evaluated every 3 months until the end of the study. The rate of patients with HBsAg loss was defined as the primary endpoint criteria.ResultsAt week 26, no patient achieved HBsAg seroconversion in either group. At week 52, one patient in the monotherapy group was HBsAg-negative but there was none in the combination therapy group. The monotherapy group showed significantly better liver function recovery results than the combination therapy group. At week 78, one patient in the combination group had HBsAg seroconverted. At week 104, only three patients in the combination therapy group were HBsAg-negative compared with one patient in monotherapy. The mean alanine aminotransferase and aspartate aminotransferase levels and transient elastography values decreased significantly compared with baseline. Both groups showed a favorable decrease in alpha-fetoprotein (monotherapy: 4.5 [2.8, 7.1] vs. 2.2 [1.8, 3.1] ng/mL, P < 0.001; combination therapy: 5.7 [3.0, 18.8] vs. 3.2 [2.0, 4.3] ng/mL, P < 0.001) and an improved result of liver biopsy examination scores. The combination group showed a better improvement in histology compared with the monotherapy group (mean transient elastography value 6.6 [4.9, 9.8] vs. 7.8 [5.4, 11.1] kPa, P = 0.028). But there was no significant difference in HBsAg conversion rate (1.8% [1/56] vs. 4.1% [3/73], P = 0.809) and HBeAg conversion rate (12.5% [7/56] vs. 11.0% [8/73], P = 0.787), as well as HBV-DNA, sustained virologic response (93.2% vs. 98.5%, P = 0.150) between the two groups.ConclusionsBoth therapies supported liver function recovery and histology improvement. Combination therapy did not show better anti-viral efficacy in HBsAg or HBeAg seroconversion compared with monotherapy. However, combination therapy played a more positive role in reversing hepatic fibrosis compared with monotherapy.Trial registrationClinicalTrials.gov: NCT02849132; https://clinicaltrials.gov/ct2/show/NCT02849132