Suppression of HBV by Tenofovir in HBV/HIV Coinfected Patients: A Systematic Review and Meta-Analysis

Background:Hepatitis B coinfection is common in HIV-positive individuals and as antiretroviral therapy has made death due to AIDS less common, hepatitis has become increasingly important. Several drugs are available to treat hepatitis B. The most potent and the one with the lowest risk of resistance appears to be tenofovir (TDF). However there are several questions that remain unanswered regarding the use of TDF, including the proportion of patients that achieves suppression of HBV viral load and over what time, whether suppression is durable and whether prior treatment with other HBV-active drugs such as lamivudine, compromises the efficacy of TDF due to possible selection of resistant HBV strains.Methods:A systematic review and meta-analysis following PRISMA guidelines and using multilevel mixed effects logistic regression, stratified by prior and/or concomitant use of lamivudine and/or emtricitabine.Results:Data was available from 23 studies including 550 HBV/HIV coinfected patients treated with TDF. Follow up was for up to seven years but to ensure sufficient power the data analyses were limited to three years. The overall proportion achieving suppression of HBV replication was 57.4%, 79.0% and 85.6% at one, two and three years, respectively. No effect of prior or concomitant 3TC/FTC was shown. Virological rebound on TDF treatment was rare.Interpretation:TDF suppresses HBV to undetectable levels in the majority of HBV/HIV coinfected patients with the proportion fully suppressed continuing to increase during continuous treatment. Prior treatment with 3TC/FTC does not compromise efficacy of TDF treatment. The use of combination treatment with 3TC/FTC offers no significant benefit over TDF alone

Suppression of HBV by Tenofovir in HBV/HIV coinfected patients : a systematic review and meta-analysis

Background: Hepatitis B coinfection is common in HIV-positive individuals and as antiretroviral therapy has made death due to AIDS less common, hepatitis has become increasingly important. Several drugs are available to treat hepatitis B. The most potent and the one with the lowest risk of resistance appears to be tenofovir (TDF). However there are several questions that remain unanswered regarding the use of TDF, including the proportion of patients that achieves suppression of HBV viral load and over what time, whether suppression is durable and whether prior treatment with other HBV-active drugs such as lamivudine, compromises the efficacy of TDF due to possible selection of resistant HBV strains. Methods: A systematic review and meta-analysis following PRISMA guidelines and using multilevel mixed effects logistic regression, stratified by prior and/or concomitant use of lamivudine and/or emtricitabine. Results: Data was available from 23 studies including 550 HBV/HIV coinfected patients treated with TDF. Follow up was for up to seven years but to ensure sufficient power the data analyses were limited to three years. The overall proportion achieving suppression of HBV replication was 57.4%, 79.0% and 85.6% at one, two and three years, respectively. No effect of prior or concomitant 3TC/FTC was shown. Virological rebound on TDF treatment was rare. Interpretation: TDF suppresses HBV to undetectable levels in the majority of HBV/HIV coinfected patients with the proportion fully suppressed continuing to increase during continuous treatment. Prior treatment with 3TC/FTC does not compromise efficacy of TDF treatment. The use of combination treatment with 3TC/FTC offers no significant benefit over TDF alone

Funnel plot of standard error against proportion undetectable at one year – all study arms (with pseudo 95% confidence limits).

<p>Funnel plot of standard error against proportion undetectable at one year – all study arms (with pseudo 95% confidence limits).</p

Results available for meta-analysis.

<p>S: number of HBV viral load test results showing viral suppression (below the level of detection).</p><p>N: number of patients with a HBV viral load test performed.</p

Characteristics of included studies.

<p>RCT: Randomised controlled trial. GS: Gilead Sciences. R: Roche. GSK: GlaxoSmithKline. NS: not stated.</p>a<p>Copies/mL converted to IU/mL by dividing by 5.</p>b<p>The limit of detection of the HBV viral load assays used fell during the course of follow up in two studies.</p>c<p>Individual patient data available.</p>d<p>National Institutes of Health/National Institute on Drug Abuse.</p>e<p>Commonwealth Department of Health and Ageing (Canberra, Australia).</p>f<p>supported in part by National Institute of Allergy and Infectious Diseases.</p>g<p>Medical Student Summer Research Training Program, supported through grants from the National Institutes of Health; Wake Forest University School of Medicine Departments, Centers, and Institutes; and private gifts.</p>h<p>Swiss National Science Foundation through the Swiss HIV Cohort Study, the Wilsdorf, Sidaide, and de Brocard Foundations, Geneva, from the Departments of Social Affairs and Economics, Geneva.</p>i<p>In part by the Adult AIDS Clinical Trials Group (ACTG) funded by the National Institute of Allergy and Infectious Diseases; virology support funding by the NIH/NIAID and the Adult ACTG Central Group; the Birmingham VA Medical Center, UAB CFAR core clinic and laboratory facilities; and NIDDK UCSF Liver Center.</p>j<p>Italian Ministry of University.</p>k<p>In part by the German BMBF Network of Competence for Viral Hepatitis (Hep Net).</p

Log of HBV viral load assay cut-off against proportion undetectable at one year.

<p>Log of HBV viral load assay cut-off against proportion undetectable at one year.</p

Multivariate logistic regression analysis of effects of prior and concomitant 3TC/FTC on virological suppression.

<p>Monotherapy: patients treated with TDF without concomitant 3TC/FTC, i.e. groups A and C.</p><p>Dual therapy: patients treated with TDF with concomitant 3TC/FTC, i.e. groups B and D.</p><p>3TC/FTC naïve: patients not previously exposed to 3TC/FTC before TDF treatment, i.e. groups A and B.</p><p>Prior 3TC/FTC exposure: patients previously exposed to 3TC/FTC before TDF treatment, i.e. groups C and D.</p><p>OR: odds ratio.</p><p>CI: confidence interval The effects comparing groups A and C and comparing groups A and B in year 3 were non-estimable as there is only one patient in group A.</p

Forest plots of study arms included in the meta-analysis at years 1–3.

<p>Forest plots of study arms included in the meta-analysis at years 1–3.</p