Tenofovir Alafenamide Versus Tenofovir Disoproxil Fumarate for Preventing Vertical Transmission in Chronic Hepatitis B Mothers: A Systematic Review and Meta-Analysis

Abstract

Objective: International guidelines recommend maternal tenofovir disoproxil fumarate (TDF) therapy accompanied by infant immunoprophylaxis to prevent hepatitis B virus (HBV) mother-to-child transmission (MTCT) in highly viremic mothers. However, pooled analyses for tenofovir alafenamide (TAF) effects and comparisons between the 2 regimens are lacking.

Design: In this meta-analysis, pairs of independent reviewers performed multiple database searches from inception to 31 March 2024 and extracted data from cohort studies and randomized controlled trials (RCTs) in highly viremic mothers. The outcomes of interest were the reduction of MTCT and safety in the TDF-treated, TAF-treated, and control groups.

Results: We included 31 studies with 2588 highly viremic mothers receiving TDF, 280 receiving TAF, and 1600 receiving no treatment. Compared to the control, TDF therapy reduced the MTCT rate in infants aged 6-12 months (risk ratio: 0.10, 95% confidence interval [CI] .07-.16). Pairwise meta-analysis between TAF and TDF revealed similar effects on reducing MTCT (risk ratio: 1.09, 95% confidence interval .16-7.61). Network meta-analysis showed equal efficacy of the 2 regimens in reducing MTCT (risk ratio: 1.09, 95% CI .15-7.65). The surface under the cumulative ranking curve revealed TDF as the best regimen compared with TAF (probability ranking: .77 vs .72), while receiving a placebo during pregnancy had the lowest efficacy (probability ranking 0.01). There were no safety concerns for mothers and infants in all regimens.

Conclusions: Compared to placebo or no treatment, maternal TDF and TAF prophylaxis are equally effective and without safety concerns in reducing MTCT in highly viremic mothers.

Keywords: TAF; TDF; hepatitis B virus; mother-to-child transmission; pregnancy.

Figure 1.

Study selection process. This figure depicts the data selection process for systematic review and meta-analysis through the search of multiple databases. A total of 6289 citations were identified across 5 databases. Following the application of inclusion and exclusion criteria, 31 studies were ultimately selected and included in the meta-analysis. § Three studies published both interim and long-term outcome reports (original articles) on the same cohorts. Abbreviations: non-RCTs, non-randomized controlled trials; RCTs, randomized controlled trials.

Figure 2.

Efficacy of maternal TDF or TAF prophylaxis in preventing MTCT. Assessment of MTCT rates after maternal prophylaxis with TDF or TAF, stratified by study design (RCTs and non-RCTs). A, Efficacy of TDF by study design. B, Efficacy of TAF by study design. Abbreviations: CI, confidence interval; MTCT, mother-to-child transmission; Non-RCTs, non-randomized controlled trials; RCT, randomized controlled trial; TAF, tenofovir alafenamide; TDF, tenofovir disoproxil fumarate; Yes/No, events numbers/no events numbers.

Figure 3.

Efficacy of initiating TDF therapy at the second vs the third trimesters. Comparison of MTCT rates when maternal TDF prophylaxis was initiated before, at, or after gestational week 28. TAF data were not included due to all studies initiating maternal prophylaxis at gestational week 28. A, Efficacy of TDF therapy by the timing of initiating the therapy. B, Head-to-head comparison of earlier vs later initiation of TDF therapy. Abbreviations: AFTER, initiation time of TDF therapy after 28 wks; AT, initiation time of TDF therapy at 28 wks; BEFORE, initiation time of TDF therapy before 28 wks; CI, confidence interval; PLA, placebo; TDF, tenofovir disoproxil fumarate; Yes/No, events numbers/no events numbers.

Figure 4.

Forest plots of infants' congenital malformation and prematurity rates. Paired comparison of infant negative outcomes between fetal exposure to TDF and placebo (or no treatment) or between fetal exposure to TDF and fetal exposure to TAF. Major outcomes included congenital malformation and prematurity. A, Congenital malformations rates for studies comparing TDF therapy vs control. B, Prematurity rates for studies comparing TDF therapy vs control. C, Congenital malformation rates for studies comparing TAF therapy vs TDF therapy. D, Prematurity rates for studies comparing TDF therapy vs TAF therapy. Abbreviations: CI, confidence interval; TAF, tenofovir alafenamide; TDF, tenofovir disoproxil fumarate; Yes/No, events numbers/no events numbers.

Figure 5.

Forest plot of ALT flares by the time of TDF cessation. Only data for TDF vs control were analyzed for postpartum ALT flares, which were stratified by the time of TDF cessation. Because all 4 of the studies on TAF included in the current review had the same design and discontinued antiviral therapy at delivery, the comparison could not be made for the different time points of TAF cessation. Abbreviations: ALT, alanine aminotransferase; CI, confidence interval; TAF, tenofovir alafenamide; TDF, tenofovir disoproxil fumarate; Yes/No, events numbers/no events numbers.