High hepatitis B virus (HBV) DNA plasma levels and hepatitis B e antigen (HBeAg) carriage are the main risk factors of mother-to-child transmission (MTCT) of HBV. Antivirals can decrease HBV DNA levels and prevent HBV MTCT. Current guidelines recommend initiating antiviral prophylaxis when maternal HBV DNA level is above 200,000 IU/mL (5.3 log IU/mL); however, the optimal duration of treatment is unknown. Within a randomized trial, we assessed the changes of HBV DNA levels in HBeAg+ pregnant women receiving either tenofovir disoproxil fumarate (TDF) or placebo during pregnancy through the early postpartum period.
HBV DNA was retrospectively quantified in HBsAg and HBeAg positive and HIV-negative pregnant women enrolled in a phase III, placebo-controlled, double-blind, randomized clinical trial assessing the efficacy and safety of TDF 300 mg once daily versus placebo from 28 weeks’ gestation through 2 months post-partum (NCT01745822). Samples were selected from all women assigned to the TDF arm and a randomly selected subset of women on placebo. HBV DNA plasma levels were measured at baseline (28 weeks), during the TDF course at weeks 32 and 36, delivery, and months 1 and 2 postpartum, and after TDF discontinuation at 3, 4, 6 and 12 months postpartum. HBV DNA levels were measured blind to the randomized arm using the RealTime HBV assay (Abbott Molecular Inc., IL, USA).
Of 331 women enrolled, 168 were randomized to TDF and 163 to placebo. Median HBV DNA levels in women on TDF decreased from 8.1 log IU/mL at baseline to 4.9 log IU/mL at 32 weeks, 4.2 at 36 weeks, 3.9 at delivery, 3.4 at 1 month and 3.3 at 2 months post-partum. After discontinuation of TDF, median HBV DNA level returned to baseline levels within one month. In the placebo arm median HBV DNA levels were unchanged during pregnancy and the postpartum period. In the TDF arm, 99 of 162 women (61%, exact 95% confidence interval [CI] 53% to 69%) had HBV DNA <200,000 IU/mL at 32 weeks, 133 of 158 (84%, CI 78% to 89%) at 36 weeks and 142 of 161 (88%, CI 82% to 93%) at delivery.
In our study, more than 85% of pregnant women receiving TDF from 28 weeks’ gestation achieved HBV DNA levels below 200,000 IU/mL prior to delivery.