Combination Of Lamivudine Research Articles

Rescue therapy for lamivudine‐resistant chronic hepatitis B: Comparison between entecavir 1.0 mg monotherapy, adefovir monotherapy and adefovir add‐on lamivudine combination therapy

There have been no reports comparing the therapeutic results of adefovir (ADV) and entecavir (ETV) rescue therapy for patients with lamivudine (LAM)-resistant chronic hepatitis B (CHB). We aimed to compare the cumulative efficacy and resistance of ETV 1.0 mg monotherapy, ADV monotherapy and ADV add-on LAM combination therapy in LAM-refractory patients. One hundred and four patients were included in the following three treatment groups; group 1 (n = 24), LAM was switched to ETV (1.0 mg once a day); group 2 (n = 44), LAM was switched to ADV (10 mg once a day); and group 3 (n = 36), ADV was added to LAM (10 mg once a day). After 6 months of rescue treatment, alanine aminotransferase normalization was observed in 75.0%, 65.9% and 74.3% of patients receiving ETV monotherapy, ADV monotherapy and ADV add-on therapy, respectively. A significantly higher log(10)HBV-DNA drop at 6 months occurred in the ADV add-on group compared with the ETV group. The rate of HBV-DNA polymerase chain reaction undetectability (<300 copies/mL) 6 months after initiation of ETV monotherapy, ADV monotherapy and ADV add-on therapy was 33.3%, 27.3% and 68.6%, respectively (P = 0.003). The cumulative HBeAg seroconversion rate was significantly higher in ADV add-on/ADV monotherapy groups compared with the ETV monotherapy group (P = 0.022). Viral breakthrough and genotypic resistance were detected in six (25.0%) and six (13.6%) patients in the ETV and ADV monotherapy groups, whereas no cases of genotypic resistance were detected in ADV add-on group 24 months after initiation of antiviral treatment (P < 0.01). Adefovir add-on treatment in patients with LAM-resistant CHB suppresses HBV replication more effectively than ETV or ADV monotherapy. Additionally, no genotypic resistance was detected in the ADV add-on group.

Lamivudine or adefovir dipivoxil alone or combined with immunoglobulin for preventing hepatitis B recurrence after liver transplantation

Recurrence of hepatitis B virus (HBV) infection in the liver graft is a grave complication following liver transplantation for HBV cirrhosis. Hepatitis B immunoglobulin (HBIg) seems effective in increasing survival after liver transplantation. HBIg and anti-viral drugs are given alone or in combination for its prevention. To assess the benefits and harms of different regimens for preventing HBV reactivation following liver transplantation. We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, and Science Citation Index Expanded until February 2010. We attempted to identify further trials by reviewing the reference lists and contacting the principal authors of identified trials. Randomised clinical trials addressing benefits and harms of lamivudine or adefovir dipivoxil alone or in combination with hepatitis B immunoglobulins (HBIg) for preventing recurrent HBV infection in patients who are liver transplanted due to HBV infection with or without hepatocellular carcinoma. Two authors independently assessed the trials for risk of bias and extracted data. We contacted study authors whenever information was lacking. We collected information on adverse events. The primary outcomes were all-cause mortality and reappearance of hepatitis B surface antigen in serum after liver transplantation. Relative risks were calculated from individual trials. Four trials, recruiting 136 participants, were included. Two trials compared lamivudine alone versus HBIg alone. Randomisation was performed one week after transplantation in one of the trials and after six months after transplantation in another; from transplantation until randomisation, HBIg alone was given to all patients in the two trials. A third trial compared combination treatment with lamivudine and HBIg versus lamivudine alone after one month of combination treatment, and a fourth trial compared the combination of lamivudine and HBIg versus a combination of lamivudine and adefovir dipivoxil after at least 12-month of lamivudine and HBIg combination treatment. Statistically significant differences were not detected in any of the comparisons and outcomes. All trials were open-labelled, and none of the trials were adequately powered to show a difference in HBV recurrence. No meta-analyses were performed since the identified trials assessed different comparisons. This review could not derive clear evidence from randomised clinical trials for the treatment of patients with chronic HBV following liver transplantation for preventing recurrence of HBV infection. Large randomised clinical trials comparing long-term combination treatment to each of the monotherapy alone, including the newer antiviral drugs, are needed.

Lamivudine plus adefovir or entecavir for patients with chronic hepatitis B resistant to lamivudine and adefovir

Little is known about the optimal management of patients with chronic hepatitis B (CHB) who developed multiple-drug resistance. We assessed 91 patients with compensated CHB who developed adefovir-resistant mutations during adefovir monotherapy for lamivudine-resistant CHB. Of these, 41 were treated with a combination of lamivudine plus adefovir (LAM+ADV group) and 50 were treated with entecavir monotherapy (ETV group). There were no significant differences between the two groups in baseline characteristics, including serum HBV DNA levels (p>0.05). The rate of virologic non-response (HBV DNA reduction <1 log(10) IU/ml at 6 months) was significantly greater in the LAM+ADV than in the ETV group (51.2% vs. 16.0%, p<0.01). At 12 months, HBV DNA declined less in the LAM+ADV than in the ETV group (-1.49+/-1.78 vs. -3.47+/-2.13 log(10) IU/ml, p<0.01). Only 12.2% and 22.0% of patients in the LAM+ADV and ETV groups, respectively, achieved complete virologic response (HBV DNA <60 IU/ml) at 12 months. Multivariable analysis showed that LAM+ADV group (OR=0.08, CI=0.02-0.28) and the presence of the rtA181V/T mutation (OR=0.21, CI=0.05-0.91) were independently associated with a decreased rate of virologic response (HBV DNA <2000 IU/ml) at 12 months. In patients with CHB resistant to lamivudine and adefovir, combination therapy with these two drugs was not effective and was inferior to entecavir monotherapy in suppressing HBV DNA. However, the response to entecavir monotherapy was also not optimal. These results emphasize the importance of preventing the development of multidrug-resistant HBV and of exploration for adequate combination therapy in treatment of multidrug-resistant CHB.

Cerebellar Atrophy Associated With Human Immunodeficiency Virus Infection

A 30-YEAR-OLD WOMAN known to have human immunodeficiency virus infection for 10 years presented with a 3-month history of stumbling, poor coordination, falls, and dysarthria. She had been starting and stopping use of several human immunodeficiency virus medications since her diagnosis, including a combination of lopinavir and ritonavir and a combination of zidovudine, lamivudine, and abacavir sulfate, but had not taken any medications for 3 years before presentation. She had no family history of similar illness. The results of physical examination were notable for severe dysarthria, nystagmus, finger-nosefinger and heel-knee-shin dysmetria, intention tremor, and impaired rapid alternating movements. She had severe truncal ataxia and was unable to stand. She had no cognitive, sensory, or motor deficits. Head computed tomography (Figure 1) and magnetic resonance imaging (Figure 2) revealed severe cerebellar atrophy. Fluid-attenuated inversion recovery magnetic resonance images, T2 sequences, and postcontrast images revealed no abnormalities except for cerebellar atrophy. Cerebrospinal fluid analysis revealed no pleocytosis, with a protein level of 0.053 g/dL (to convert to grams per liter, multiply by 10.0), and the patient had a negative VDRL test result. Her CD4 cell count was 186/μL, and her human immunodeficiency virus RNA viral load was 210 000 copies/mL. The results of her toxicology screening, autoimmune screening, and paraneoplastic antibody panel were negative; vitamin B12, vitamin E, and thyrotropin levels were normal.

Resistance pathways of human immunodeficiency virus type 1 against the combination of zidovudine and lamivudine

A better understanding of human immunodeficiency virus type 1 drug-resistance evolution under the selective pressure of combination treatment is important for the design of long-term effective treatment strategies. We applied Bayesian network learning to sequences from patients treated with the reverse transcriptase inhibitor combination of zidovudine (AZT) and lamivudine (3TC) to identify the role of many treatment-selected mutations in the development of resistance. Based on the Bayesian network structure, an in vivo fitness landscape was built, reflecting the necessary selective pressure under treatment, to evolve naive sequences to sequences obtained from patients treated with the combination. This landscape, combined with an evolutionary model, was used to predict resistance evolution in longitudinal sequence pairs. In our analysis, mutations 41L, 70R, 184V and 215F/Y were identified as major resistance mutations to the combination of AZT and 3TC, as they were associated directly with treatment experience. The network also suggested a possible role in resistance development for a number of novel mutations. Estimated fitness, using the landscape, correlated significantly with in vitro resistance phenotype in genotype-phenotype pairs (R(2)=0.70). Variation in predicted evolution under selective pressure correlated significantly with observed in vivo evolution during AZT plus 3CT treatment. In conclusion, we confirmed current knowledge on resistance development to the combination of AZT and 3CT, but additional novel mutations were identified. Moreover, a model to predict resistance evolution during AZT and 3CT treatment has been built and validated.

The Impact of Once-Nightly Versus Twice-Daily Dosing and Baseline Beliefs About HAART on Adherence to Efavirenz-Based HAART Over 48 Weeks: The NOCTE Study

To determine the impact of once-nightly versus twice-daily dosing and beliefs about highly active antiretroviral therapy (HAART) on adherence to efavirenz-based HAART in antiretroviral-naive patients. A multicenter, open-label, 48-week, randomized controlled trial. Participants were randomized to receive once nightly didanosine plus lamivudine, or twice-daily combivir (zidovudine plus lamivudine) both in combination with efavirenz. Medication Event Monitoring Systems were used to compile drug-dosing histories. Beliefs about HAART (necessity and concerns) were measured at baseline using validated questionnaires. Perceptions of HAART intrusiveness were assessed after 4 weeks. Eighty-seven patients were randomized (44 once-nightly and 43 twice-daily). Overall adherence was higher among the once-nightly arm (P = 0.0327). Eighty-one percent once-nightly and 62% twice-daily patients persisted with treatment for 48 weeks (P = 0.0559). Regimen execution was similar between both arms. Participants were significantly less likely to persist with HAART if their initial concerns about HAART were high relative to their perceived need for treatment (P = 0.025). The difference in adherence observed between once-nightly and twice-daily dosing was driven by a difference in persistence with treatment. Psychological preparation for starting HAART should address patients' perceptions of necessity for HAART and concerns about adverse effects to maximize persistence with treatment.

Long-term adefovir dipivoxil monotherapy for up to 5 years in lamivudine-resistant chronic hepatitis B

Large clinical studies assessing long-term adefovir dipivoxil salvage monotherapy in patients with lamivudine-resistant chronic hepatitis B (CHB) are lacking, particularly in patients positive for hepatitis B e antigen (HBeAg). We assessed the efficacy and resistance profile of adefovir dipivoxil monotherapy for up to 5 years in a large cohort of Korean patients with lamivudine-resistant CHB. A total of 320 patients (81.3% HBeAg-positive; 100% genotype C) with confirmed genotypic lamivudine-resistant CHB were switched to adefovir dipivoxil 10 mg once daily. Liver function tests and HBV DNA were monitored every 3 months. Genotypic resistance to adefovir dipivoxil was performed in patients with detectable HBV DNA. The overall cumulative virological response rate at 5 years of adefovir dipivoxil therapy was 48.8%. The virological response rate was significantly higher in HBeAg-negative patients (62.0% versus 45.9%; P=0.010). Most cases of virological response (131/134, 97.8%) occurred within the first 36 months of therapy. The 5-year cumulative probability of genotypic resistance and virological breakthrough was 65.6% and 61.8%, respectively. Predictive factors for a virological response included baseline HBeAg seronegativity, HBV DNA< or =8 log(10) copies/ml and achievement of an on-treatment initial virological response. Adefovir dipivoxil salvage monotherapy for lamivudine-resistant CHB resulted in a modest cumulative virological response rate at 5 years, which was associated with progressive antiviral resistance. Consequently, adefovir monotherapy is not preferable as a first-line strategy for lamivudine resistance where combination lamivudine plus adefovir dipivoxil therapy is available.

Pharmacokinetic Characterization of Three Doses of Tipranavir Boosted with Ritonavir on Highly Active Antiretroviral Therapy in Treatment-Experienced HIV-1 Patients

Purpose: This study characterized the pharmacokinetic effects, safety, and antiretroviral activity of three different doses of the nonpeptidic protease inhibitor tipranavir, in combination with ritonavir administered twice daily for 28 days, on a number of triple-combination regimens containing a nonnucleoside reverse transcriptase inhibitor (efavirenz or nevirapine) plus two nucleoside reverse transcriptase inhibitors (abacavir, didanosine, lamivudine, stavudine, and zidovudine) or a three nucleoside reverse transcriptase inhibitor combination (zidovudine, lamivudine, and abacavir).Methods: The study enrolled 208 HIV-1–positive patients who had been on stable antiretroviral treatment for at least 12 weeks prior to study entry and had an HIV-1 RNA load of δ 20,000 copies/mL. The patients were randomized to receive one of three dose combinations of tipranavir and ritonavir (1250/100 mg, 750/100 mg, and 250/200 mg) in addition to their antiretroviral (ARV) regimen for the next 22 days. The effects of twice-daily tipranavir and ritonavir combinations on the steady-state pharmacokinetics of the antiretrovirals were assessed by comparing pharmacokinetic parameters at baseline and after 3 weeks of coadministration.Results: No clinically relevant changes were observed in the Cmin, Cmax, or AUC parameters for nevirapine, efavirenz, lamivudine, stavudine, or didanosine, when coadministered with tipranavir and ritonavir at the dose combinations studied. All three dose combinations of tipranavir and ritonavir decreased the systemic exposure of abacavir (by 35% to 44%) and zidovudine (by 31% to 42%). Consistent with previous tipranavir studies, gastrointestinal adverse events were those most frequently observed. These reactions tended to be mild, with the majority being of Grade 1, and only 8 being of Grade 3 or 4 in intensity. Virologic response improved from 40.4% of participants at baseline with <50 copies/mL to 67.6% at Day 28 of study following addition of tipranavir and ritonavir.Conclusions: Tipranavir coadministered with ritonavir has been demonstrated to be safe, effective, and pose little potential for clinically meaningful drug interactions when added to the highly active antiretroviral therapy regimens containing nevirapine, efavirenz, lamivudine, stavudine, or didanosine.

Differential effects of interferon and lamivudine on serum HBV RNA inhibition in patients with chronic hepatitis B

Lamivudine and interferon have been widely used for the treatment of patients with chronic HBV infection. Serum HBV RNA is detected during lamivudine therapy as a consequence of interrupted reverse transcription and because RNA replicative intermediates are unaffected by the drug. In this study, we aimed to determine the detectability of serum HBV RNA during sequential combination therapy of interferon and lamivudine. HBV DNA and RNA in serum samples were quantified by reverse transcription of HBV nucleic acid extract and real-time PCR. Samples were analysed every 2 weeks to 3 months from three groups of patients: 10 male patients treated with nucleoside analogue monotherapy for 44-48 weeks (5 with lamivudine and 5 with entecavir), 6 males on sequential interferon and lamivudine combination therapy, and 3 males on lamivudine monotherapy for 20-24 weeks. HBV RNA was not detectable in any patients before treatment, but became detectable in 15 during antiviral treatment. Among the three groups, pre-treatment HBV DNA (8.1 +/-2.4 versus 7.7 +/-1.4 versus 5.1 +/-0.3 log(10) copies/ml; P=0.06), treatment and follow-up durations (45.5 +/-2.0 versus 49.7 +/-5.6 versus 48.7 +/-6.4 weeks; P=0.32) were comparable. HBV RNA was detectable at the end of treatment or follow-up in all patients with monotherapy, but in none of those with sequential combination therapy (100% versus 0%; P<0.001). Compared with lamivudine therapy with detectable serum HBV RNA in patients with chronic HBV infection, interferon treatment might reduce HBV DNA replication through the inhibition of HBV RNA replicative intermediates, resulting in the loss of serum HBV RNA.

Comparison of different immunoprophylaxis regimens after liver transplantation with hepatitis B core antibody-positive donors: A systematic review

Orthotopic liver transplantation (OLT) recipients without hepatitis B virus (HBV) infection who receive liver grafts from antibody to hepatitis B core antigen-positive [HBcAb(+)], hepatitis B surface antigen-negative [HBsAg(-)] donors have an increased risk of developing de novo hepatitis B infection. We compared the 2 most commonly employed prophylactic regimens-lamivudine (LAM) monotherapy and hepatitis B immunoglobulin (HBIG)+LAM combination therapy-to determine the relative efficacies of these 2 protocols in preventing de novo hepatitis B infection. A comprehensive search of the Cochrane Database of Systematic Reviews, MEDLINE (1966 to June 2009), and bibliographies of retrieved trials was conducted. Eligible studies included OLT recipients who received HBcAb(+) liver grafts and were treated prophylactically with either LAM monotherapy or HBIG+LAM combination therapy. 13 studies were identified as meeting the eligibility criteria. The rates of de novo hepatitis B infection, mortality, and mortality due to de novo hepatitis B infection were assessed. The incidence of de novo hepatitis B infection was 2.7% (n = 73) in patients receiving LAM-only prophylaxis versus 3.6% (n = 110) in patients receiving HBIG+LAM combination therapy. In the HBIG+LAM group, the dose and duration of HBIG therapy were highly variable. The median follow-up time for the LAM monotherapy group was 25.4 months with a range of 14.78 to 27.6 months, whereas the median follow-up time for the LAM+HBIG group was 31.1 months with a range of 15.3 to 38.5 months. The risk of developing de novo hepatitis B infection based on the pretransplant recipient HBV serology in each treatment group could not be calculated because of incomplete data and the limited number of de novo hepatitis B infection cases in the series reviewed. In conclusion, on the basis of these findings, we conclude that published studies have not shown HBIG+LAM combination therapy to be more effective than LAM-only treatment. Nucleoside analogue monotherapy should therefore be considered when one is treating HBV(-) patients who have received liver allografts from HBcAb(+) donors.

Overlap/Switch to Adefovir Monotherapy for Lamivudine-resistant Patients Who Responded to Combination Therapy: A Pilot Controlled Study

The aim of this study was to investigate the outcome of overlap/switch to adefovir dipivoxil (ADV) monotherapy for chronic hepatitis B (CHB) patients with lamivudine (LAM)-resistant HBV, who responded to LAM plus ADV combination therapy. In 29 of 35 LAM-resistant CHB patients, serum HBV-DNA levels decreased to <3.7 log genome equivalent (LGE)/mL at 12 months after LAM plus ADV combination therapy, defined as complete virological response (CVR). The 29 CVR patients were randomly allocated to continuation of combination therapy or switch to ADV monotherapy within 12 months. The cumulative rates of sustained CVR were compared between the two groups. The follow-up duration after randomization was 19.3-36.7 months (median, 28.2 months) for the combination group and 21.0-36.4 months (29.0 months) for the overlap/switch group. The cumulative rate of sustained CVR during the follow-up period was 100% in all patients of both groups. The total medical expenses during follow-up after randomization were median US$20,949 for the combination group and US$16,107 for the overlap/switch group (p=0.012). Overlap/switch to ADV monotherapy sufficiently repressed the replication of LAM-resistant mutants without the development of ADV-resistant mutants. The rate of sustained CVR was not influenced by treatment regimen (continuation of combination therapy or switching to ADV monotherapy), the duration of the overlap period, or patient and virological characteristics. In LAM-resistant CHB patients who achieved CVR to LAM plus ADV combination therapy, CVR was maintained after overlap/switch to ADV monotherapy, suggesting that it could be a useful regimen for such patients.

Adverse drug reactions to antiretroviral therapy in aids patients at a tertiary care hospital in India: A prospective observational study

To identify the adverse drug reactions (ADRs) to antiretroviral therapy (ART) and to assess their impact on treatment compliance in patients with HIV/AIDS. Two hundred and thirty-five (235) AIDS patients who received ART were monitored for ADRs over a period of 6 months. The incidence and nature of ADRs occurring with different ART regimens were recorded. We also assessed the severity, causality as well as the impact of ADRs on the patients' compliance. Of 235 patients receiving ART, 90.6% patients experienced ADRs. A total of 618 ADRs involving various systems were observed. A majority were related to gastrointestinal (42.39%) and central nervous (25.57%) system. 23.1% ADRs were severe in intensity. Severe ADRs occurred in 41 out of 235 (17.4%) patients necessitating drug withdrawal. A majority of the patients (87.8%) who complained of severe ADRs received combination of stavudine, lamivudine and nevirapine. Causality assessment revealed 6.63% ADRs were probable and 93.3% ADRs were possible. Non-compliance due to ADRs was observed in 28.9% patients. Myriad ADRs are associated with ART which leads to poor patient compliance. With the increasing access to ART in India, it is prudent that antiretroviral drugs are used judicially with regular monitoring of ADRs.

Pharmacokinetics of intramuscular and intravenous HBIG: Which implications for practice?

A major achievement for patients transplanted for hepatitis B virus (HBV) associated end-stage liver disease is the successful prevention of reinfection with high dose of hepatitis B immunoglobulin (HBIG). The introduction of lamivudine in combination with HBIG reduces recurrence rates to less than 5% at 5 years. Currently, this combination is the accepted standard regimen in most transplantation units. However, a major drawback of this therapy is that high-dose intravenous (IV) HBIG is very expensive. Several strategies have been explored to reduce such costs. These include withdrawal of HBIG at some time after transplantation while continuing lamivudine, vaccination of patients prior to cessation of HBIG and substitution of high-dose IV HBIG by low-dose intramuscular (IM) HBIG. It has been demonstrated that crucial pharmacokinetic parameters, including anti-HBs antibodies through levels at time of HBIG re-administration, do not differ significantly after IV and IM administration in stable hepatitis B surface antigen (HBsAg) negative patients with at least 12 months follow-up after orthotopic liver transplantation, confirming the cost-effectiveness of IM HBIG administration. Recent studies suggest that, compared with combination of HBIG plus lamivudine prophylaxis, the combination of adefovir plus lamivudine prophylaxis provides equivalent protection against HBV reinfection with better tolerability at a significantly lower cost. Nonetheless, HBIG continue to be the cornerstone of HBV recurrence prevention.

Human immunodeficiency virus and renal transplantation

CASE PRESENTATION A 48-year-old African-American man with chronic human immunodeficiency virus (HIV) infection since 1987 was referred to our center for renal transplant evaluation. HIV-associated nephropathy had been diagnosed 8 years earlier by renal biopsy. Hemodialysis had been initiated 3 years earlier. Past medical history was significant for hypertension and hyperlipidemia. Before transplantation, total cholesterol was 178mg per 100ml, low-density lipoprotein was 40mg per 100ml, and high-density lipoprotein was 67mg per 100ml without lipid-lowering therapy. The patient reported no history of earlier opportunistic infection (OI), malignancy, or co-infection with hepatitis B virus (HBV) or hepatitis C virus (HCV). He had been treated with highly active antiretroviral therapy (HAART) since 1990. After numerous treatment failures, virologic suppression was finally achieved with a combination of lamivudine, abacavir, efavirenz, and lopinavir/ritonavir.

Reversible Reduction of Nevirapine Plasma Concentrations During Rifampicin Treatment in Patients Coinfected With HIV-1 and Tuberculosis

Nevirapine (NVP) plasma levels are reduced in patients receiving rifampicin (RFM) for tuberculosis (TB) treatment. We determined variations over time of the pharmacokinetic parameters of NVP in patients who receive RFM. HIV-1-infected patients with CD4+ T-lymphocyte count <or=100 cells per microliter and TB diagnosis received standard anti-TB therapy and a fixed-dose combination of stavudine, lamivudine, and NVP. Full NVP pharmacokinetic curves were calculated at 4 (T1) and 10 weeks (T2) of combined therapy and at 4 (T3) and 26 weeks after termination of anti-TB therapy. In 16 enrolled subjects, the median value of the area under the curve of NVP was reduced by 25.6% at T1 compared with NVP alone (43.7 vs. 58.7 microg x mL(-1) x h(-1); P = 0.02). The reduction was only 7.5% at T2 (54.3 vs. 58.7 microg x mL(-1) x h(-1); P = 0.17). The median C trough was reduced of 19.5% at T1 compared with T3 (3.3 vs. 4.2 microg/mL; P = 0.02) and of 7.1% at T2 compared with T3 (3.9 vs. 4.2 microg/mL; P = 0.17). The proportion of subjects with C trough values <or=3 microg/mL was 31.2% (5 of 16), 40.0% (6 of 15), and 7.7% (1 of 13) at T1, T2, and T3, respectively. The reduction of the area under the curve of NVP during concomitant RFM treatment substantially decreases over time.

OL-028 Therapeutic efficacy of combination of lamivudine with interferon-α for HBeAg positive chronic hepatitis B: systematic review and meta-analysis of randomized trials

OL-028 Therapeutic efficacy of combination of lamivudine with interferon-α for HBeAg positive chronic hepatitis B: systematic review and meta-analysis of randomized trials

Combination of Lamivudine and adefovir therapy in HBeAg-positive chronic hepatitis B patients with poor response to adefovir monotherapy

At present, there is no consensus treatment for patients who have poor response to Adevofir dipivoxil (ADV) monotherapy and no ADV-associated mutation. The purpose of this study was to evaluate the effect of a new therapeutic strategy combining Lamivudine (LAM) and ADV in patients with HBeAg-positive chronic hepatitis B (CHB) and poor response to ADV monotherapy. Thirty-one patients with chronic hepatitis B with HBV DNA > or = 10(4) copies/mL after 48 weeks of ADV monotherapy were included and received ADV plus LAM for 24 weeks. Compared with ADV monotherapy, ADV + LAM had an improved response rate at weeks 12 and 24 - compared with baseline, the median decrease in HBV-DNA level at week 12 and 24 were 1.27 and 2.03 log respectively. The virological response (VR) rate (HBV-DNA level <10(3) copies/mL) was 6.5% and 35.5% at weeks 12 and 24, respectively; the biochemical response (BR) rate (normalization of alanine aminotransferase levels) was 67.8% and 100%, respectively; the HBeAg loss rate was 6.9% and 34.5%, respectively; and the seroconversion rate (from HBeAg to HBeAb) was 3.5% and 6.9% respectively. No ADV-associated mutation was detected at baseline. After combination therapy for 24 weeks, no LAM-resistant or ADV-resistant mutations were detected. Only one patient had a mild adverse reaction. In conclusion, optimization of therapy combining LAM and ADV may be a good choice for patients with hepatitis B who have a poor response to ADV monotherapy.

Early HBeAg Loss During Peginterferon α-2b Therapy Predicts HBsAg Loss: Results of a Long-Term Follow-Up Study in Chronic Hepatitis B Patients

Treatment with pegylated interferon (PEG-IFN) alpha-2b results in hepatitis B e antigen (HBeAg) loss in 36% of patients at 6 months post treatment. The aim of this study was to determine whether a long-term response to PEG-IFN is dependent on the timing of HBeAg loss. A total of 91 patients treated with PEG-IFN alpha-2b alone (100 microg per week) and 81 patients treated with PEG-IFN alpha-2b and lamivudine (100 mg/day) for 52 weeks were enrolled in this study. Patients were initially followed up at 4-week intervals and had one additional long-term follow-up (LTFU) visit (mean: 3.03+/-0.77 years 26 weeks post treatment). Of the 172 patients included, 78 patients (46%) did not have loss of HBeAg, 47 (27%) lost HBeAg within 32 weeks, and 47 patients (27%) had loss of HBeAg after week 32. At LTFU, patients with HBeAg loss< or =32 weeks had hepatitis B virus DNA of <400 copies/ml significantly more often than did those who lost HBeAg after week 32 (47 vs. 21%, respectively; P=0.009). Hepatitis B surface antigen (HBsAg) negativity was also observed significantly more often in patients with early HBeAg loss (36 vs. 4%, respectively, P<0.001). Early HBeAg loss tended to occur more often in patients treated with PEG-IFN and lamivudine combination therapy than in those treated with PEG-IFN alone (35 vs. 21%; P=0.10), as did HBsAg loss (15 vs. 8%; P=0.14). Early PEG-IFN-induced HBeAg loss results in a high likelihood of HBsAg loss and may be associated with more profound viral suppression during the first 32 weeks of therapy in patients treated with lamivudine combinations.

Very early mortality in patients starting antiretroviral treatment at primary health centres in rural Malawi

To report on the cumulative proportion of deaths occurring within 3 months of starting antiretroviral treatment (ART) and to identify factors associated with such deaths, among adults at primary health centres in a rural district of Malawi. Retrospective cohort study: from June 2006 to April 2008, deaths occurring over a 3-month period were determined and risk factors examined. A total of 2316 adults (706 men and 1610 women; median age 35 years) were included in the analysis and followed up for a total of 1588 person-years (PY); 277 (12%) people died, of whom 206 (74%) people died within 3 months of initiating ART (cumulative incidence: 13.0; 95% confidence interval: 11.3-14.8 per 100 PY of follow-up). Significant risk factors associated with early deaths included male sex, WHO stage 4 disease, oesophageal or persistent oral candidiasis and unexplained presumed or measured weight loss >10%. One in every 3 patients who either died or was lost to follow up had unexplained weight loss >10%, and survival in this group was significantly different from patients without this condition. Seven in 10 individuals initiating ART at primary health centres die early. Specific groups of patients are at higher risk of such mortality and should receive priority attention, care and support.

Evaluation of Chai Shao Liu Jun Tang for the treatment of chronic hepatitis B

To evaluate the effect of Chai Shao Liu Jun Tang in combination with Lamivudine for the treatment chronic hepatitis B (CHB) patients. 405 CHB patients in Guangdong Provincial Hospital were randomly divided into 2 groups, 220 in the treated group, and 185 in the control group. The control group was treated with Lamivudine for 18 months. The treated group was treated with Lamivudine in combination with Chai Shao Liu Jun Tang for 18months. At the 3rd, 6th, 9th, 12th and 18th month during the treatment, the clinical symptoms, ALT normalization rate, HBeAg seroconversion rate, the proportion of patients with undetectable serum HBV DNA, and YMDD mutation rate were observed. ALT normalization rates at the 3rd, 6th, 12th, 18th month of the treatment group (69.5%, 85.9%, 90.5%, 82.7%) were higher than those in the control group (50.3%, 65.4%, 78.4%, 69.7%; P < 0.01). HBeAg seroconversion rate, rate of HBV DNA undetectable, and YMDD mutation rate at he 12th and18th month are 77.7%, 57.7%, 25.5%, 6.8%; 86.8%, 74.1%, 33.2%, 8.6% in the treatment group, and 54.6%, 36.8%, 13.0%, 14.6%; 69.2%, 37.3%, 19.5%, 20.5% in the control group (P < 0.01, or P < 0.05). Compared to lamivudine alone, Cai Shao Liu Ju Tang in combination with lamivudine is more effective and induces less YMDD mutation rate in CHB patients.