Lamivudine Group Research Articles

Hepatoprotective potential of lamivudine through activation of gamma-glutamyltransferase and down-regulation of p53 in HepG2 cells

The liver is a crucial metabolic organ that aids in detoxification, produces energy, synthesizes essential proteins, and is essential for maintaining good health. Since hepatocytes are the main type of cell found in liver tissue, maintaining their safety is essential for the general health of livers. The hepato-protective qualities of lamivudine shield the liver from stressful situations. The current study aimed to assess lamivudine's protective effects on HepG2 cells subjected to ethanol damage. Lamivudine was given to HepG2 cells after they were cultivated and subjected to ethanol-induced damage. Cell viability was assessed using the MTT, Crystal Violet, and Trypan Blue tests. The results of the MTT experiment demonstrated that lamivudine administration improved the rate of cell viability in a dose-dependent manner at 25, 50, and 100 μg/mL (0.570±0.0205; 0.73 ±0.02; 0.897±0.0206, respectively). According to the Crystal Violet test, lamivμdine-treated cells had higher cell viability than untreated cells; the rates were around 0.38 ± 0.01, 0.516 ± 0.0305, and 0.656 ± 0.041 in a dose dependant manner. The Trypan Blue assay results also confirmed that treatment with lamivudine at 25 μg/mL, 50 μg/mL, and 100 μg/mL led to a increase in the viability of cells compared to the injury group (183.66±5.50; 151±3.61; 115±5, respectively). Pretreatment of HepG2 cells with lamivudine during 100 µg/mL concentration exposure resulted in near-normalization of p53 expression levels (24.73±0.60), GSH levels (28.83±1.16), and in hepatic activity levels of GGT (21.23±1.12) compared to control. In immunofluorescence microscopy, the 100 µg/mL lamivudine group showed the most significant reduction in fluorescence intensity. Lamivudine provided convenient features in protecting HepG2 cells against ethanol-triggered liver damage by enhancing cell survival and antioxidant enzyme activities.

Analysing the efficacy and tolerability of dolutegravir plus either rilpivirine or lamivudine in a multicentre cohort of virologically suppressed PLWHIV.

We aimed to investigate and compare the efficacy and safety of two dolutegravir-based two-drug regimens: dolutegravir + lamivudine versus dolutegravir + rilpivirine. We analysed a cohort of people living with HIV (PLWHIV) switching to dolutegravir + lamivudine or dolutegravir + rilpivirine. We excluded from the analysis PLWHIV with no available pre-switch genotypic test or with a known resistance mutation to one of the study drugs. We evaluated incidence of virological failure (VF) and treatment discontinuation (TD), as well as changes in immunological and metabolic parameters. We enrolled 592 PLWHIV: 306 in the lamivudine group and 286 in the rilpivirine group. We observed nine VFs in the lamivudine group [1.4 VF per 100 patient-years of follow-up (PYFU)] and four VFs in the rilpivirine group (0.6 VF per 100 PYFU). Subsequent genotypic analysis showed no acquired resistance-associated mutations in those experiencing VF. Estimated probability of maintaining virological suppression at 144 and 240 weeks were 96.6% and 92.7%, respectively, in the lamivudine group and 98.7% and 98.7%, respectively, in the rilpivirine group (log-rank P = 0.172). The estimated probability of maintaining study regimen at Week 240 was 82.3% in the lamivudine group and 85.9% in the rilpivirine group (log-rank P = 0.018). We observed a significant improvement in CD4+ cell count at Week 240 in the lamivudine group (P = 0.012); in the rilpivirine group we registered a significant increase in CD4/CD8 ratio (P = 0.014). Both analysed strategies are effective and safe as switch strategies in clinical practice, with a low incidence of VF and a favourable immunological recovery, even in the long term.

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.

Tolerability and Adherence of Antiretroviral Regimens Containing Long-Acting Fusion Inhibitor Albuvirtide for HIV Post-Exposure Prophylaxis: A Cohort Study in China.

IntroductionThere have been no prospective clinical studies investigating adherence and tolerability of HIV post-exposure prophylaxis (PEP) in China. Tolerability, adherence, and transmitted drug resistance are concerns, especially when single-tablet regimen (STR) usage is low. The present study aimed to explore the safety, tolerability, and adherence of regimens containing albuvirtide (ABT) compared with recommended non-STR antiretrovirals for HIV PEP.MethodsThis was a prospective, open-label, multicenter cohort study. The subjects were stratified into 3 groups based on their preference: ABT + Dolutegravir (DTG) (Group 1), ABT + Tenofovir disoproxil fumarate (TDF) + Lamivudine (3TC) (Group 2), and DTG + TDF + 3TC (Group 3). All enrolled subjects received PEP within 72 h after exposure and continued for 28 days, and were followed-up for 12 weeks.ResultsA total of 330 participants were enrolled in the three groups. Most participants were male (87.2%). Sexual contact was the most frequent mode of exposure (91.9%). The average time from exposure to treatment was 26.8 ± 19.5 h. There were no statistically significant differences between the three study groups with respect to completion of oral medication at 28 days. The 28-day completion rate was shown to be significantly higher with ABT versus oral (88.9% vs. 64.0%; p < 0.0001), and adherence with ABT was 94.4% compared to 75.7% with oral PEP (p < 0.0001). Subjects in ABT-containing Group 1 exhibited higher adherence than those in Group 3 (87.3% vs. 72.9%; p < 0.05). None of the participants reported serious adverse drug reactions which led to withdrawal from the study. All the drug regimens were found to be safe and well tolerated. No HIV incident case was observed during the study period.ConclusionsABT-containing regimens (ABT + DTG or ABT + TDF + 3TC) offer a good option for HIV PEP due to higher completion rates and adherence than the DTG + TDF + 3TC regimen. The overall safety was comparable and acceptable among the three groups.RegistrationThe study was registered in Chinese Clinical Trial Registry with registration number (ChiCTR1900022881, http://www.chictr.org.cn/showprojen.aspx?proj=37395).

Neurocognitive and Neuroarchitectural Changes in the Prefrontal Cortex of Wistar Rats Treated with Highly Active Antiretroviral Therapy

The use of highly active antiretroviral therapy has proven to be highly effective in the treatment of human immunodeficiency virus 1 (HIV-1) infection. However, its impact on cognition has not been fully explored. This study was designed to assess the impacts of antiretroviral therapy on cognitive function and histoarchitecture of the prefrontal cortex of Wistar rats. Forty adult male Wistar rats weighing 180-200 g were randomly assigned to 4 groups: control, tenofovir, lamivudine and efavirenz (n=10), which received 1 ml distilled water and 6 mg/kg, 6 mg/kg and 12 mg/kg, respectively. Spatial memory scores were assessed using the Y-maze test. Following behavioural studies, the animals were euthanized, and their whole brains harvested. The prefrontal cortex was sectioned and processed for oxidative stress, histological and immunohistochemical analyses. There was a significant decrease in percentage alternation evaluated from the right/wrong decisions scored from the tenofovir and lamivudine groups, compared to the control group (p&lt;0.05). malondialdehyde (MDA) and reduced glutathione (GSH) levels were elevated following lamivudine and tenofovir exposure in the rats’ prefrontal cortices, respectively, compared to control (p&lt;0.05). There were also significant alterations of cortical pyramidal cells in the tenofovir and lamivudine groups. Additionally, marked astrogliosis with increased glial fibrillary acidic protein expression was observed, consistent with the structural alterations, especially in the lamivudine group. Our findings suggest that, of the three highly active antiretroviral therapy (HAART) drugs studied, lamivudine may be a major culprit in the progressive neurological damage and cognitive impairment in HIV-infected individuals on HAART.

Efficacy of entecavir verses lamivudine prophylaxis in preventing hepatitis B virus reactivation in patients with allogeneic stem cell transplant

Immunosuppressive therapy has been the main stay of treatment in patients with hematological malignancies. Reactivation of occult hepatitis B infection (HBV), is commonly encountered with stem cell transplant recipients with anti CD20 agents, with history of resolved HBV infection. We aimed to find the efficacy of nucleos(t)ide analogues lamivudine (LVD) and entecavir (ETV) in preventing the HBV flare up when given prophylactically. Patients who received allogeneic stem cell transplant were evaluated. Sixty patients, thirty in each group who received LVD or ETV prophylaxis were included in the study. All the baseline and post-transplant data was evaluated which includes anti -CD20 agent exposure, duration of prophylaxis of each drugs and clinical and virological follow up post transplantation. Serum ALT, HBsAg, anti HBs and HBV DNA were the parameters measured. The median clinical and virological follow up in each group was 24 months. LVD or ETV was given during the entire follow up period. There was no reactivation during the prophylaxis period, however 2 patients in LVD group showed detectable viral DNA post prophylaxis withdrawal. The clinical outcome of both LVD and ETV reveals equal efficacy in preventing HBV reactivation. However screening is mandatory before chemotherapy. HBs Ag-negative/anti-HBc-positive patients require ALT monitoring during the entire chemotherapy.

Islatravir in combination with doravirine for treatment-naive adults with HIV-1 infection receiving initial treatment with islatravir, doravirine, and lamivudine: a phase 2b, randomised, double-blind, dose-ranging trial

Islatravir is a nucleoside reverse transcriptase translocation inhibitor in development for the treatment and prevention of HIV-1 infection. We aimed to assess the efficacy and safety of islatravir-based regimens for the treatment of HIV-1. We did a phase 2b, randomised, double-blind, comparator-controlled, dose-ranging trial at 24 clinics or hospitals in four countries (Chile, France, the UK, and the USA). Treatment-naive adults (≥18 years) with plasma HIV-1 RNA concentrations of at least 1000 copies per mL, CD4 T-cell counts of at least 200 cells per mL, and a calculated creatinine clearance of at least 50 mL/min (all within 60 days before study treatment) were eligible for inclusion. Participants were randomly assigned (1:1:1:1) with a block size of four via an interactive voice and web response system to receive oral treatment with one of three doses of islatravir (0·25 mg, 0·75 mg, or 2·25 mg) plus doravirine (100 mg) and lamivudine (300 mg) or to doravirine (100 mg) plus lamivudine (300 mg) plus tenofovir disoproxil fumarate (TDF; 300 mg) once daily with placebo (part 1). Treatment groups were stratified according to screening HIV-1 RNA concentration (≤100 000 copies per mL or >100 000 copies per mL). After at least 24 weeks of treatment, participants taking islatravir who achieved an HIV-1 RNA concentration lower than 50 copies per mL switched to a two-drug regimen of islatravir and doravirine (part 2). All participants and study investigators were masked to treatment in part 1; in part 2, the islatravir dose was masked to all participants and investigators, but the other drugs were given open label. The primary efficacy outcomes were the proportions of participants with an HIV-1 RNA concentration lower than 50 copies per mL at weeks 24 and 48 (US Food and Drug Administration snapshot approach). The primary safety outcomes were the number of participants experiencing adverse events and the number of participants discontinuing study drug owing to adverse events. All participants who received at least one dose of any study drug were included in the analyses. This trial is ongoing, but closed to enrolment of new participants; herein, we report study findings through 48 weeks of treatment. This trial is registered with ClinicalTrials.gov, NCT03272347. Between Nov 27, 2017, and April 25, 2019, 121 participants (mean age 31 years [SD 10·9], 112 [93%] male, 92 [76%] white, 27 [22%] with HIV-1 RNA concentration >100 000 copies per mL) were randomly assigned: 29 to the 0·25 mg, 30 to the 0·75 mg, and 31 to the 2·25 mg islatravir groups, and 31 to the doravirine, lamivudine, and TDF group. At week 24, 26 (90%) of 29 participants in the 0·25 mg islatravir group, 30 (100%) of 30 in the 0·75 mg islatravir group, and 27 (87%) of 31 in the 2·25 mg islatravir group achieved HIV-1 RNA concentrations lower than 50 copies per mL compared with 27 (87%) of 31 in the doravirine plus lamivudine plus TDF group (difference 2·8%, 95% CI -14·9 to 20·4, for the 0·25 mg islatravir group; 12·9%, -1·6 to 27·5, for the 0·75 mg islatravir group; and 0·3%, -17·9 to 18·5, for the 2·25 mg islatravir group). At week 48, these data were 26 (90%) of 29 in the 0·25 mg islatravir group, 27 (90%) of 30 in the 0·75 mg islatravir group, and 24 (77%) of 31 in the 2·25 mg islatravir group compared with 26 (84%) of 31 in the doravirine plus lamivudine plus TDF group (difference 6·1%, 95% CI -12·4 to 24·4, for the 0·25 mg islatravir group; 6·2%, -12·2 to 24·6, for the 0·75 mg islatravir group; and -6·1%, -27·1 to 14·8, for the 2·75 mg islatravir group). 66 (73%) of participants in the islatravir groups combined and 24 (77%) of those in the doravirine plus lamivudine plus TDF group reported at least one adverse event. Two participants in the 2·25 mg islatravir group and one participant in the doravirine plus lamivudine plus TDF group discontinued owing to an adverse event. No deaths were reported up to week 48. Treatment regimens containing islatravir and doravirine showed antiviral efficacy and were well tolerated regardless of dose. Doravirine in combination with islatravir has the potential to be a potent two-drug regimen that warrants further clinical development. Merck, Sharp, & Dohme Corp, a subsidiary of Merck & Co., Inc.

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.

Assessment of prevalence of SARS-CoV-2 Infection in patients on anti-HBV (lamivudine) treatment: A questionnaire based survey

Assessment of prevalence of SARS-CoV-2 Infection in patients on anti-HBV (lamivudine) treatment: A questionnaire based survey - IJMMTD- Print ISSN No: - 2581-4753 Online ISSN No:- 2581-4761 Article DOI No:- 10.18231/j.ijmmtd.2021.005, IP International Journal of Medical Microbiology and Tropical Diseases-IP Int J Med M

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.

Modeling cerebellar limb dysmetria and impaired spatial memory in rats using lamivudine: A preliminary study

Background and aimNeurodegeneration has been associated with the use of combination antiretroviral therapy (cART). This study is aimed at determining if any constituent of cART can induce cerebellar limb dysmetria and spatial memory impairments. Materials and methodsForty adult male Wistar rats were randomly grouped into four (n = 10): control (distilled water 0.5 mL); Tenofovir (6 mg/kg); Lamivudine (6 mg/kg) and Efavirenz (12 mg/kg). The following neurobehavioral studies were conducted: open field, beam walk, and Morris water maze. Immunohistochemistry of CD 68 and GFAP were used to test for neuroinflammation and neurodegeneration. ResultsThere was marked increase in pyknotic pyramidal cells of the hippocampus and ghost Purkinje cells in the cerebellum of treatment groups. There was also a significant increase in oxidative stress in lamivudine and efavirenz groups. In addition, Lamivudine caused a significant increase of microglial and astrocytic activity (p < 0.001, 0.05 respectively) compared to control. The open field test showed a significant decrease (p < 0.0001) of the line crossing performance in the efavirenz, lamivudine and tenofovir (with means: 26.4, 4.6, 17.4 respectively) compared to control (50.6). There was also a significant decrease in the grooming (p < 0.05) and rearing (p < 0.01) in lamivudine group. Whereas, walk latency increased in efavirenz (p < 0.01), and lamivudine (p < 0.0001) compared to control. While hind limb slips significantly increased in efavirenz (p < 0.05) and lamivudine (p < 0.0001) compared with control group. Likewise, Lamivudine and Tenofovir exposed groups experienced a significant delay in the time to identify the hidden platform in compared to control (p < 0.05). ConclusionLamivudine altered efferent stimuli along the cerebellospinal tracts thereby causing motor impairments. The degenerating Purkinje fibers may have induced marked neurodegeneration in the hippocampus resulting in impaired spatial memory.

Fixed-dose combination bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir-containing regimens for initial treatment of HIV-1 infection: week 144 results from two randomised, double-blind, multicentre, phase 3, non-inferiority trials

In the primary week-48 analyses of two phase 3 studies, coformulated bictegravir, emtricitabine, and tenofovir alafenamide was non-inferior to a dolutegravir-containing regimen in treatment-naive people with HIV. We report week-144 efficacy and safety results from these studies. We did two double-blind, active-controlled studies (now in open-label extension phase). Study 1 randomly assigned (1:1) HLA-B*5701-negative adults without hepatitis B virus co-infection to receive coformulated bictegravir 50 mg, emtricitabine 200 mg, and tenofovir alafenamide 25 mg, or coformulated dolutegravir 50 mg, abacavir 600 mg, and lamivudine 300 mg once daily. Study 2 randomly assigned (1:1) adults to bictegravir, emtricitabine, and tenofovir alafenamide, or dolutegravir 50 mg given with coformulated emtricitabine 200 mg and tenofovir alafenamide 25 mg. We previously reported non-inferiority at the primary endpoint. Here, we report the week-144 secondary outcome of proportion of participants with plasma HIV-1 RNA less than 50 copies per mL at week 144, by US Food and Drug Administration Snapshot algorithm, analysed in the same manner. These studies were registered with ClinicalTrials.gov, NCT02607930 and NCT02607956. 629 participants were randomly assigned and treated in study 1 (314 to bictegravir, emtricitabine, and tenofovir alafenamide, and 315 to dolutegravir, abacavir, and lamivudine) and 645 in study 2 (327 to bictegravir, emtricitabine, and tenofovir alafenamide, 325 to dolutegravir, emtricitabine, tenofovir alafenamide). At week 144, bictegravir, emtricitabine, and tenofovir alafenamide was non-inferior to both dolutegravir-containing regimens for efficacy. In study 1, 256 (82%) of 314 participants had plasma HIV-1 RNA less than 50 copies per mL in the bictegravir, emtricitabine, and tenofovir alafenamide group and 265 (84%) of 315 in the dolutegravir, abacavir, and lamivudine group (difference -2·6%, 95% CI -8·5 to 3·4). In study 2, 262 (82%) of 320 participants had plasma HIV-1 RNA less than 50 copies per mL in the bictegravir, emtricitabine, and tenofovir alafenamide group and 273 (84%) of 325 in the dolutegravir, emtricitabine, and tenofovir alafenamide group (difference -1·9%, -7·8 to 3·9). In both studies, no participant had treatment-emergent resistance to study drugs up to week 144. All treatment regimens were well tolerated with additional exposure. Adverse events that led to study drug discontinuation were reported for no participants in the bictegravir, emtricitabine, and tenofovir alafenamide group versus five (2%) of 315 in the dolutegravir, abacavir, and lamivudine group (study 1), and six (2%) of 320 in the bictegravir, emtricitabine, and tenofovir alafenamide versus six (2%) of 325 in the dolutegravir, emtricitabine, and tenofovir alafenamide group (study 2). In study 1, statistically significant differences were observed in median changes from baseline in fasting total cholesterol (14 mg/dL vs 10 mg/dL; p=0·034), direct LDL (21 mg/dL vs 14 mg/dL; p=0·004), and total cholesterol to HDL ratio (-0·1 vs -0·3; p=0·007) at week 144; no differences were observed between groups in study 2. Weight gain was seen across all treatment groups in both studies, with no differences in median changes from baseline in weight at week 144 for either study. These long-term data support the use of bictegravir, emtricitabine, and tenofovir alafenamide as a safe, well tolerated, and durable treatment for people with HIV, with no emergent resistance. Gilead Sciences.

Efficacy and Safety of Lamivudine or Telbivudine in Preventing Mother-to-Child Transmission of Hepatitis B Virus: A Real-World Study.

Background There are few large sample studies evaluating the safety and efficacy of lamivudine (LAM) or telbivudine (LdT) in preventing hepatitis B mother-to-child transmission (MTCT) in highly viremic mothers in the third trimester of pregnancy in real-world settings. The purpose of this study was to analyze a large sample size of HBV-infected mothers to better understand the safety and efficacy of LAM and LdT under the aforementioned criteria. Methods During the period of November 2008 to November 2017, we retrospectively enrolled mothers with HBV DNA > 1 × 106 IU/mL who received LAM or LdT during the third trimester of pregnancy and compared them to untreated mothers. All mothers were divided into the three following groups: the LAM group, the LdT group, and the control group. Results A total of 2624 HBV-infected mothers were enrolled in the study, with 363 in the LAM group, 1283 in the LdT group, and 978 in the control group. The MTCT rates were significantly lower in the LAM or LdT group than that in the control group (0.4% or 0.3% versus 9.0%, P < 0.001). Infants born to untreated mothers had a significantly higher risk of HBV infection (OR = 28.6, 95% CI: 10.4–78.7, P < 0.001). There were no significant differences in perinatal complications between the three groups (P > 0.05). There were also no differences for gestational age or infants' height, weight, Apgar scores, or birth defect rates. Postpartum discontinuation of antiviral therapy did not seem to increase the risk of postpartum alanine aminotransferase (ALT) flare. Conclusion LAM or LdT treatment initiated in the third trimester for mothers with HBV DNA > 1 × 106 IU/mL was equally safe and effective in preventing MTCT.

Antiretroviral Therapy‐Induced Cerebellar Disorders: Efavirenz, Lamivudine, Tenofovir Disoproxil Fumarate; Which is Guilty?

IntroductionCombination antiretroviral therapy (cART) has transformed the landscape of managing Human Immunodeficiency Virus (HIV) infection. However, there have been various reports on the deleterious activities of the therapy on patients' cerebellar function. Therefore, the aim of this study is to ascertain the effects of individual administration of tenofovir disoproxil fumarate, Lamivudine and efavirenz (ingredients of cART) on the cerebellum.Materials and MethodsForty adult Wistar rat were used for this study. They were divided into four groups according to the substances administered: distilled water, tenofovir disoproxil fumarate, lamivudine and efavirenz. After 35 days of administration, the animals underwent open field and beam walk tests. They were euthanized and the brain was prepared for oxidative stress assay, histological (Giemsa stain, Hematoxylin and Eosin stain) and immunohistochemical (GFAP and Dopamine) analysis. Ethical clearance protocol number: CMUL/HREC/03/17/113.ResultsThere was significant decrease in rearing, grooming, and line crossing in treatment groups most especially lamivudine group compared to control group. The latency, right and left hind limb slips increased significantly (p&lt;0.01) in lamivudine group compared to control. There was a statistically significant decrease in the superoxide dismutase levels in the efavirenz group compared to control group (p&lt;0.001). Tenofovir showed a significant increase in catalase level compared to the control group (p&lt;0.001). Tenofovir, lamivudine and Efavirenz showed a significant increase in lipid peroxidation level compared to the control group. Histology analysis showed a degeneration/decrease in the granular and Purkinje cells in treatment groups compared to the control group. There was also a significant proliferation of astrocytes and a decrease in dopamine expression in Lamivudine groups compared to control.ConclusionThis study shows that tenofovir disoproxil fumarate and efavirenz cause various toxicities on the motor function of the cerebellum. However, Lamivudine is the major culprit in cART‐induced cerebellar disorders.Support or Funding InformationResearch reported in this publication was supported by the Fogarty International Center of the National Institutes of Health under Award Number D43TW010134, through the Building Research and Innovation in Nigeria's Science (BRAINS).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Lamivudine use in pregnant HBsAg-females effectively reduces maternal viremia

Background and study aimsMother-infant hepatitis B virus (HBV) transmission is the current leading cause of chronic infection. We aimed to assess the efficacy of lamivudine use in hepatitis B surface antigen (HBsAg)-positive pregnant women to decrease viral load and thus aid in the prevention of transmission. Patients and methodsA study of 73 mother-infant pairs. All mono-infected HBsAg-positive pregnant females of any age, who were a candidate for lamivudine during pregnancy were recruited, and a comparison group of HBsAg-positive pregnant females who did not receive any antiviral treatment. All infants received HBV immunoglobulin and vaccine at birth and completed the vaccination schedule and tested after 6 months of age. HBV viral markers and viral load quantitation were performed to all enrolled participants. Results34 (46.6%) females were enrolled in the lamivudine group; 9 (26.5%) received the drug in the last trimester, 25 (73.5%) all through. The comparison group was 39 (53.4%) females; 32 (82.1%) were not candidate for antiviral during pregnancy, and 7 (17.9%) were diagnosed late near delivery. Seventy-one infants tested after full immunization, with their ages ranged between 6.5 and 18 months. Only one infant (1.4%) was positive for HBsAg and HBV DNA in the non-treated group. Maternal viremia near delivery showed a significant reduction in cases that used lamivudine during pregnancy. ConclusionThe use of lamivudine during pregnancy can effectively lower maternal viral load. Timely conducted post-vaccination serological testing is crucial to detect positive cases and immunize susceptible infants.

Growth in HIV-1-exposed but uninfected infants treated with lopinavir–ritonavir versus lamivudine: a secondary analysis of the ANRS 12174 trial

The tolerance of antiretroviral drugs in infants must be carefully evaluated. In previous studies of children with HIV type 1 (HIV-1) less weight gain was observed in children given lopinavir-ritonavir-based combinations than those given nevirapine. We aimed to compare the effects of lopinavir-ritonavir and lamivudine on growth in HIV-exposed uninfected infants included in the ANRS 12174 trial. ANRS 12174 was a multicentre, randomised, controlled trial of infant prophylaxis to prevent HIV-1 transmission by breastfeeding done at four antenatal clinics in Burkina Faso, South Africa, Uganda, and Zambia. HIV-exposed uninfected infants born to asymptomatic mothers not eligible for antiretroviral therapy (CD4 count >350 cells per μL) were randomly assigned (1:1) to receive lopinavir-ritonavir or lamivudine 7 days after birth, with stratification by country. In a prespecified secondary analysis, we assessed the effect of lopinavir-ritonavir and lamivudine on the growth of these infants from day 7 until cessation of breastfeeding (maximum treatment time 12 months) in the modified intention-to-treat population, which included all children correctly enrolled with at least one follow-up anthropometric measurement. We compared the growth of infants, defined as children's WHO-defined length-for-age Z score (LAZ), weight-for-length Z score (WAZ), and weight-for-age Z score (WLZ). We used linear mixed effect and β spline-regression models to compare growth between the treatment groups. The trial is registered with ClinicalTrials.gov, number NCT00640263. 1273 HIV-exposed uninfected infants and their mothers were enrolled between Nov 16, 2009, and May 7, 2013, of whom 1266 (99%) infants were included in the modified intention-to-treat analysis (630 assigned to lopinavir-ritonavir, 636 assigned to lamivudine). Baseline characteristics of the infants and mothers were similar across the two treatment groups. No differences in least-squares (LS) mean LAZ were identified between the treatment groups at any timepoint. LS mean WLZ was significantly lower in the lopinavir-ritonavir group than the lamivudine group at 26 weeks (difference -0·22 [95% CI -0·34 to -0·09], p=0·0006) and 50 weeks (-0·25 [-0·47 to -0·04], p=0·02). LS mean WAZ was also significantly lower in the lopinavir-ritonavir group than the lamivudine group at 26 weeks (difference -0·18 [95% CI -0·30 to -0·05], p=0·01) and 50 weeks (-0·24 [-0·45 to -0·05], p=0·02). Linear mixed models showed that lopinavir-ritonavir was associated with decreases in WLZ and WAZ over time (p<0·0001 and p=0·002), whereas spline regression models indicated that these reductions occurred early and remained constant thereafter (p<0·0001 with a knot at 44 days for WLZ; p=0·02 with a knot at 118 days for WAZ). The difference in LS mean WLZ at 50 weeks between the treatment groups was higher among girls than boys (difference -0·29 [95% CI -0·58 to 0·01], p=0·05 for girls; -0·22 [-0·53 to 0·09], p=0·18 for boys). Less weight gain was observed in infants given lopinavir-ritonavir than those given lamivudine, which is indicative of a persistent effect that could have long-term deleterious effects. This finding merits attention considering the recommendations for early and lifelong treatment of infants with HIV. French National Agency for Research on AIDS and Viral Hepatitis, the Total Foundation, the European Developing Countries Clinical Trials Partnership, and the Research Council of Norway.

Assessment of histopathological alterations in patients with chronic hepatitis B infection following long-term oral antiviral therapy.

Objectives:To evaluate the histopathological changes in the liver after oral antiviral therapy in patients with chronic hepatitis B.Methods:A total of 79 HBeAg-negative and positive patients who had been on lamivudine, entecavir, or tenofovir disoproxil for at least 3 years prior to inclusion were enrolled between March 2015 and 2016, retrospectively. There were 23 patients on lamivudine, 21 patients on entecavir, and 35 on tenofovir. All patients underwent a follow-up liver biopsy. Biochemical, serological, virological and histopathological data were recorded in all patients and were compared after at least 3 years of treatment with oral antiviral agents.Results:Histological activity index scores were reduced in patients who received lamivudine (p=0.011), entecavir (p=0.002), and tenofovir (p=0.001). Also, in contrast with a significant improvement in fibrosis scores in lamivudine (p=0.033) and tenofovir (p=0.001) groups no improvements were found in patients who received entecavir (p=0.090).Conclusion:Long term treatment with oral antiviral agents was associated with biochemical, virological, serological, and histopathological improvements. Long-term use of anti-viral agents as well as continuous suppression of HBV DNA are prerequisites for histopathological improvement.

Compare the effect of combined therapy between telbivudine plus adefovir dipivoxil and lamivudine plus adefovir dipivoxil corresponding to renal function in patients with hepatitis B virus infection

Objective: To compare the effect of combined therapy using lamivudine (LAM) plus adefovir (ADV) versus telbivudine (LdT) plus adefovir corresponding to the renal function of CHB patients. Methods: A total of 120 patients with chronic hepatitis B were enrolled. According to single daily dosing, they were divided into 4 groups: LdT + ADV group (n = 32), ADV+LdT group (n = 28), LAM + ADV group (n = 38) and ADV + LAM group (n = 22). Hepatorenal function, HBV serological markers, HBV DNA quantification, creatine kinase (CK) and other parameters were examined every 3 months. Serum alanine aminotransferase (ALT) normalization rate, undetectable HBV DNA rate, hepatitis B e antigen (HBeAg) seroconversion rate, level of serum creatinine (CR) and estimated glomerular filtration rate (eGFR) were analyzed at baseline time, and at weeks 24 and 52.Stastical data were analyzed by t- test and analysis of variance, count data using χ (2) test. Results: There was no statistically significant difference between the four groups in terms of ALT normalization rate, HBeAg seroconversion rate, undetectable HBV DNA rate at 24 and 52 weeks. Compared with baseline, at 24 weeks of treatment, there was no significant change in serum creatinine and eGFR in the 4 groups, but after 52 weeks of treatment, serum creatinine decreased in LdT + ADV and ADV + LdT groups and eGFR increased (P < 0.05); Serum creatinine in ADV and ADV + LAM increased, and eGFR was decreased than before (P < 0.05). After treatment, there was no significant difference in renal function between the four groups at 24 weeks, but at week 52, eGFR increased and serum creatinine decreased in LdT + ADV group compared with LAM + ADV group (P < 0.05); ADV + LdT Compared with ADV + LAM group, eGFR increased and serum creatinine decreased (P < 0.05). At 52 weeks of treatment, 5 patients with mildly impaired renal function in the ADV + LdT group [n = 10, eGFR 60-90 ml·min(-1) ·(1.73 m(2))(-1)] returned to normal, and none of the ADV + LAM group (n = 9) returned to normal. Conclusion: For patients with mild impaired renal function, adding LdT combined with ADV can improve renal function compared to that of LAM plus ADV.

Tenofovir alafenamide plus emtricitabine versus abacavir plus lamivudine for treatment of virologically suppressed HIV-1-infected adults: a randomised, double-blind, active-controlled, non-inferiority phase 3 trial

Abacavir and tenofovir alafenamide offer reduced bone toxicity compared with tenofovir disoproxil fumarate. We aimed to compare safety and efficacy of tenofovir alafenamide plus emtricitabine with that of abacavir plus lamivudine. In this randomised, double-blind, active-controlled, non-inferiority phase 3 trial, HIV-1-positive adults (≥18 years) were screened at 79 sites in 11 countries in North America and Europe. Eligible participants were virologically suppressed (HIV-1 RNA <50 copies per mL) and on a stable three-drug regimen containing abacavir plus lamivudine. Participants were randomly assigned (1:1) by a computer-generated allocation sequence (block size 4) to switch to fixed-dose tablets of tenofovir alafenamide (10 mg or 25 mg) plus emtricitabine (200 mg) or remain on abacavir (600 mg) plus lamivudine (300 mg), with matching placebo, while continuing to take the third drug. Randomisation was stratified by the third drug (boosted protease inhibitor vs other drug) at screening. Investigators, participants, and study staff giving treatment, assessing outcomes, and collecting data were masked to treatment group. The primary endpoint was the proportion of participants with virological suppression (HIV-1 RNA <50 copies per mL) at week 48 (assessed by snapshot algorithm), with a 10% non-inferiority margin. We analysed the primary endpoint in participants enrolled before May 23, 2016 (when target sample size was reached), and we analysed safety in all enrolled participants who received at least one dose of study drug (including patients enrolled after these dates). This study was registered with ClinicalTrials.gov, number NCT02469246. Study enrolment began on June 29, 2015, and the cutoff enrolment date for the week 48 primary endpoint analysis was May 23, 2016. 501 participants were randomly assigned and treated. At week 48, virological suppression was maintained in 227 (90%) of 253 participants receiving tenofovir alafenamide plus emtricitabine compared with 230 (93%) of 248 receiving abacavir plus lamivudine (difference -3·0%, 95% CI -8·2 to 2·0), showing non-inferiority. Few participants discontinued treatment because of adverse events: 12 (4%) of 280 participants in the tenofovir alafenimide plus emtricitabine group and nine (3%) of 276 in the abacavir plus lamivudine group. Three participants had serious, treatment-related adverse events: one each with renal colic and neutropenia in the tenofovir alafenamide plus emtricitabine group, and one myocardial infarction in the abacavir plus lamivudine group. There were no treatment-related deaths. Tenofovir alafenamide, in combination with emtricitabine and various third drugs, maintained high efficacy with a renal and bone safety profile similar to that of abacavir. In virologically suppressed patients, a regimen containing tenofovir alafenamide could be an alternative to those containing abacavir, without concern for new onset of renal or bone toxicities or hyperlipidaemia. Gilead Sciences Inc.

Efficacy and safety of Entecavir monotherapy switched from Lamivudine combined Adefovir Dipivoxil for chronic hepatitis B virus-related compensated liver cirrhosis

Objective: To observe the efficacy and safety of de novo combination of Lamivudine(LAM) and Adefovir Dipivoxil (ADV) therapy counter to Entecavir (ETV) monotherapy in patients with chronic hepatitis B (CHB)- related compensated liver cirrhosis. Methods: Patients with chronic hepatitis B-related compensated cirrhosis who were initially treated with LAM and ADV for more than 1 year were randomly assigned to two groups, one half replaced with ETV monotherapy, and the other half continued LAM and ADV co-therapy. Liver biochemistry, renal biochemistry, estimated glomerular filtration rate, alpha-fetoprotein, HBV serology markers and serum HBV DNA were measured every 3 months. Urine β2-microglobulin was measured every 6 months And retinol binding protein, followed up for 3 years. The mean values of the two groups were compared with t-test, and the rate of comparison was analyzed by x2 test. Results: A total of 580 cases were collected, 290 cases were replaced with ETV monotherapy, the other 290 patients continued to LAM and ADV combination therapy. In the ETV group, the rates of HBV DNA negative conversion at 1 year, 2 years and 3 years were 77.6%, 84.5% and 94.5% respectively, while the HBV DNA negative conversion rates at 1, 2 and 3 years in the LAM and ADV combination groups were 69.3%, 73.4% and 80.3% respectively. Among them, the negative rates of HBV DNA in the second year and the third year were P < 0.05, the difference was statistically significant. The 3-year cumulative gene-resistant rate in the ETV group was 1.4%, while the combined treatment was as high as 8.6%, and the difference was statistically significant in the two groups. The estimated value of serum creatinine and glomerular filtration rate in ETV group was followed by 3 years, and the baseline level was maintained, in the same group, the serum creatinine was higher than baseline, and the estimated value of glomerular filtration rate decreased. The results showed that there were 6.2%, 12.1%, 22.1% and 0, 0.3%, 1%, respectively, in 1, 2 and 3 years for the group of consecutive treatment and the replacement of ETV Group. The estimated glomerular filtration rate decreased by more than 30% compared with the baseline. The difference was statistically significant; the proportion of serum creatinine in the 1 year, 2 years and 3 years of the combined treatment group was 1.7%, 4.5% and 6.6%, compared with the baseline rise of > 50 μmol/l, and the ETV group was replaced in the 1 year, The values of 2 and 3 years were 0,0,0.7%, of which the 2nd and 3rd years were statistically significant; the proportion of microalbuminuria and retinol-binding protein in patients with combined treatment group was also significantly higher than that of Β2-m ETV Group. Conclusion: The initial combination of LAM and ADV therapy is inferior in terms of ETV monotherapy. Single therapy with ETV increase the rate of viral response, reduce the incidence of drug resistance, and also reduce the incidence of renal impairment in patients with chronic hepatitis B -related compensated liver cirrhosis.