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

Abstract

BackgroundHepatitis 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.MethodsA 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.ResultsData 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.InterpretationTDF 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.

Management of chronic hepatitis B infection

“…Even though these drugs are secreted at low levels in breast milk, studies on the long A meta-analysis of 23 studies also demonstrated the efficacy of tenofovir in the suppression of HBV viremia, with no impact of previous lamivudine exposure or combination with emtricitabine. 104 Although evidence from this study suggests that tenofovir may have similar efficacy to combined tenofovir and emtricitabine, combination therapy is still the preferred treatment for coinfected patients. 14 Hepatitis delta HDV is a human RNA virus that encodes the delta antigen, which is subsequently encased in an envelope within HBsAg.…”

An HBV-HIV Co-infected Patient Treated with Tenofovir-based Therapy who Achieved HBs Antigen/Antibody Seroconversion

“…The overall proportion of patients achieving suppression of HBV replication was 57.4%, 79.0%, and 85.6% at 1, 2, and 3 years, respectively (11). In addition to the high rate of virological suppression, TDF-resistance mutations, such as the combination of rtL180M, rtM204V/I, and rtA194T or N236T with A181A (12,13), are rare (14).…”

Effect of Antiretroviral HIV Therapy on Hepatitis B Virus Replication and Pathogenicity

“…A specific problem was that lamivudine remained active against HIV due to the combination therapy, while HBV - treated only with lamivudine - became rapidly resistant and caused severe hepatitis B. Further drugs were developed and today the preference to treat HIV-1/HBV is the combination of tenofovir plus emtricitabine since no HBV drug resistance has been detected in the patients after 10 years of application [22]. However, tenofovir treatment is possibly less effective in HIV patients coinfected with HBV genotype G after pretreatment with lamivudine [23].…”

“…Nearly all of the drugs used today for HBV treatment were initially developed for HIV, including the combination of tenofovir plus emtricitabine, which is as effective as tenofovir monotherapy for the long-term treatment of hepatitis B [22]. The main restriction of the present tenofovir therapy is still hepatotoxicity [29] and nephrotoxicity [24].…”