Dataset Information

Lamivudine plus tenofovir combination therapy versus lamivudine monotherapy for HBV/HIV coinfection: a meta-analysis.

ABSTRACT:

Background

Currently, there is no consensus on the efficacy and safety of lamivudine (LAM) plus tenofovir disoproxil fumarate (TDF) combination therapy versus lamivudine monotherapy in HBV/HIV coinfected patients.

Methods

A comprehensive literature search was performed in English and Chinese databases. Both relevant dichotomous and continuous variables were extracted, and the combined outcomes were expressed as a risk ratio (RR) or a standard mean difference (SMD).

Results

Eleven eligible studies were included in our analysis. For HBV-relevant outcomes, the proportion of patients with undetectable HBV, the rates of serum alanine aminotransferase (ALT) normalization and hepatitis B e antigen (HBeAg) loss were higher in the combination therapy group than the monotherapy group (RR?=?1.42, 95% CI: 1.14-1.76, P?=?0.002; RR?=?1.36, 95% CI: 1.17-1.58, P?ConclusionLAM plus TDF combination therapy was more efficacious than LAM monotherapy in HBV/HIV coinfected patients. As time passes, this difference becomes more pronounced.

SUBMITTER: Luo A

PROVIDER: S-EPMC6130076 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Publications

Lamivudine plus tenofovir combination therapy versus lamivudine monotherapy for HBV/HIV coinfection: a meta-analysis.

Luo Aoran A Jiang Xiaoyan X Ren Hong H

Virology journal 20180910 1

<h4>Background</h4>Currently, there is no consensus on the efficacy and safety of lamivudine (LAM) plus tenofovir disoproxil fumarate (TDF) combination therapy versus lamivudine monotherapy in HBV/HIV coinfected patients.<h4>Methods</h4>A comprehensive literature search was performed in English and Chinese databases. Both relevant dichotomous and continuous variables were extracted, and the combined outcomes were expressed as a risk ratio (RR) or a standard mean difference (SMD).<h4>Results</h4> ...[more]

PMID: 30201035

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Project description:BackgroundThe use of fixed-dose combination nucleoside reverse-transcriptase inhibitors (NRTIs) with a nonnucleoside reverse-transcriptase inhibitor or a ritonavir-boosted protease inhibitor is recommended as initial therapy in patients with human immunodeficiency virus type 1 (HIV-1) infection, but which NRTI combination has greater efficacy and safety is not known.MethodsIn a randomized, blinded equivalence study involving 1858 eligible patients, we compared four once-daily antiretroviral regimens as initial therapy for HIV-1 infection: abacavir-lamivudine or tenofovir disoproxil fumarate (DF)-emtricitabine plus efavirenz or ritonavir-boosted atazanavir. The primary efficacy end point was the time from randomization to virologic failure (defined as a confirmed HIV-1 RNA level > or = 1000 copies per milliliter at or after 16 weeks and before 24 weeks, or > or = 200 copies per milliliter at or after 24 weeks).ResultsA scheduled interim review by an independent data and safety monitoring board showed significant differences in virologic efficacy, according to the NRTI combination, among patients with screening HIV-1 RNA levels of 100,000 copies per milliliter or more. At a median follow-up of 60 weeks, among the 797 patients with screening HIV-1 RNA levels of 100,000 copies per milliliter or more, the time to virologic failure was significantly shorter in the abacavir-lamivudine group than in the tenofovir DF-emtricitabine group (hazard ratio, 2.33; 95% confidence interval, 1.46 to 3.72; P<0.001), with 57 virologic failures (14%) in the abacavir-lamivudine group versus 26 (7%) in the tenofovir DF-emtricitabine group. The time to the first adverse event was also shorter in the abacavir-lamivudine group (P<0.001). There was no significant difference between the study groups in the change from the baseline CD4 cell count at week 48.ConclusionsIn patients with screening HIV-1 RNA levels of 100,000 copies per milliliter or more, the times to virologic failure and the first adverse event were both significantly shorter in patients randomly assigned to abacavir-lamivudine than in those assigned to tenofovir DF-emtricitabine. (ClinicalTrials.gov number, NCT00118898.)

Project description:BackgroundThe efficacy of switching to tenofovir disoproxil fumarate (TDF) monotherapy from lamivudine (LAM) plus adefovir dipivoxil (ADV) combination therapy (stable switching) in patients with LAM-resistant chronic hepatitis B (CHB) and undetectable hepatitis B virus (HBV) DNA is not clear.MethodsIn this non-inferiority trial, patients with LAM-resistant CHB and undetectable serum HBV DNA (<20 IU/mL) for >6 months after initiating LAM+ADV combination therapy were randomized (1:2) either to continue the combination therapy (LAM+ADV group, n = 58) or switched to TDF monotherapy (TDF group, n = 111). They were followed-up with serum biochemistry tests and HBV DNA measurement at 12-week intervals for 96 weeks. The primary endpoint of this study was the proportion of patients with viral reactivation at week 96.ResultsPatients with CHB enrolled in this study (n = 169) included 74 patients with compensated liver cirrhosis. In total, 9 patients (4 in the LAM+ADV group and 5 in the TDF group) dropped-out from the study. After a mean follow-up period of 96 weeks, the proportion of HBV reactivation observed was 6.8% (4/58) in the LAM+ADV group and 4.5% (5/111) in the TDF group by using intention-to-treat analysis (difference, -2.3%; 95% CI, -9.84-5.24%). None of the subjects in either group experienced viral reactivation based on per protocol analysis. No serious adverse reactions were observed. In the subgroup analysis for estimated glomerular filtration rate (eGFR) before and after treatment, decreased eGFR was observed only in the TDF group with cirrhosis (85.22 vs. 79.83 mL/min/1.73 m2, p = 0.000).ConclusionsStable switching to TDF monotherapy yielded non-inferior results at 96 weeks compared to the results obtained with LAM+ADV combination therapy in patients with LAM-resistant CHB and undetectable HBV DNA. However, TDF monotherapy in patients with cirrhosis requires close attention with respect to renal function.Trial registrationClinicalTrials.gov NCT01732367.

Project description:Background: Hepatitis B virus (HBV) coinfection is common in HIV-positive patients. HIV infection modifies the natural course of HBV infection, leading to a faster progression of liver-related morbidity and mortality than is observed in HBV mono-infected patients. This systematic review and meta-analysis evaluates the current clinical evidence regarding the use of oral tenofovir disproxil fumarate (TDF)-based treatments in patients coinfected with HIV and HBV. Methods: We performed a comprehensive literature search in PubMed and Web of Science. Supplementary searches were conducted in Google Scholar and Clinicaltrials.gov. We conducted a random effects meta-analysis using the event rate (ER) to estimate the incidence of HBV seroconversion. A subgroup meta-analysis was performed to assess the moderate effects of demographic and disease-related variables on HBsAg loss. This review is registered in the PROSPERO database (CRD42018092379). Results: We included 11 studies in the review. The immunological effects of oral TDF-based Pre-exposure prophylaxis (PrEP) treatment in patients with HIV-HBV coinfection were 0.249 for HBeAg loss, 0.237 for HBeAg conversion, 0.073 for HBsAg loss, and 0.055 for HBsAg conversion. The factors associated with HBsAg loss were the baseline HBV viral load, participant's location, and a history of exposure to lamivudine/emtricitabine (3TC/FTC) (all p < 0.05). A trend toward a negative relationship between the baseline CD4+ T-cell count and HBsAg loss was observed (p = 0.078). Conclusion: This systematic review and meta-analysis demonstrated that TDF-containing regimens are effective at stimulating HBeAg loss (24.9%), HBeAg conversion (23.7%), HBsAg loss (7.3%), and HBsAg conversion (5.5%) in HIV-HBV coinfected patients. The moderator analysis showed that HBV viral load, the location of participants, and prior exposure to 3TC/FTC are factors associated with HBsAg loss. Asian ethnicity, prior exposure to 3TC, and a nondetectable baseline HBV viral load are associated with lower odds of HBsAg loss. Well-designed prospective cohort studies and randomized controlled trials (RCTs) with large sample sizes are required for the investigation of potential predictors and biological markers associated with strategies for achieving HBV remission in patients with HIV-HBV coinfection, which is a matter of considerable importance to clinicians and those responsible for health policies.

Project description:Background/Aim:Acute-on-chronic liver failure (ACLF-B) in spontaneous reactivation of chronic hepatitis B (SR-CHB) has high mortality. Tenofovir disoproxil fumarate (TDF) improves survival by ~40% in ACLF-B but is potentially nephrotoxic. Combining telbivudine (LDT) with TDF may negate this risk and could boost rapid viral clearance and improve clinical outcomes. Patients and Methods:Seventy consecutive patients with SR-CHB were randomized to TDF (300 mg/day, n = 35) or TDF plus LDT (600 mg/day; n = 35). In all, 25 had ACLF-B and none had option for liver transplantation. Primary endpoint was survival at 3 months. Secondary endpoints were survival at 3 months in ACLF-B, serial reduction in hepatitis B virus (HBV) DNA, hepatitis B surface antigen (HBsAg) loss and liver-related complications. Results:Overall baseline clinical and laboratory parameters in the two groups were comparable. Reduction in HBV DNA at weeks 2, 4 and 12 was independent of treatment groups and presence of ACLF-B (P < 0.01). All six patients with HBsAg loss at 12 weeks had lower HBV DNA at baseline and none had ACLF-B. Patients with no ACLF-B had more rapid decline in bilirubin and alanine aminotraminase at week 2 compared with ACLF-B. Patients on TDF plus LDT showed significant improvement in AKI on follow-up (five of six patients) compared with TDF monotherapy (none of six patients) and had less reduction in estimated glomerular filtration rate at week 12. Eight of 10 patients with liver-related deaths received TDF monotherapy (P = 0.02). New-onset septic shock, TDF monotherapy, e-antibody positivity, and higher baseline model for end-stage liver disease score were predictors of mortality in ACLF-B. None had treatment-related severe adverse effects. Conclusion:Addition of LDT to tenofovir is safe and may be renoprotective in spontaneous reactivation of hepatitis B. Combination therapy improves survival in ACLF-B despite comparable HBV DNA suppression to tenofovir monotherapy.

Dataset Information

Lamivudine plus tenofovir combination therapy versus lamivudine monotherapy for HBV/HIV coinfection: a meta-analysis.

Background

Methods

Results

Publications

Lamivudine plus tenofovir combination therapy versus lamivudine monotherapy for HBV/HIV coinfection: a meta-analysis.

Similar Datasets

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