iTAP was a double-blind randomized clinical trial assessing the efficacy and safety of tenofovir disoproxil fumarate (TDF) to prevent perinatal HBV transmission in hepatitis B virus (HBV) chronically infected pregnant women with HBeAg (NCT01745822). We report secondary endpoints through 12 months after delivery.
HBsAg and HBeAg positive women (age ≥18 years, ALT ≤60 IU/L, negative HIV and hepatitis C serology, creatinine clearance >50 mL/min) were randomized to receive TDF 300mg or placebo, once daily from 28 weeks gestation through 2 months postpartum in 17 hospitals in Thailand. Infants received HBIg at birth, and HB vaccine at birth, 1, 2, 4 and 6 months of age. After their 6-month visit, mothers were seen at 12 months and infants at 9 and 12 months. Infant HBV DNA PCR was performed at 9 months and an HBsAg test at 12 months.
Of the 331 (168 TDF, 163 placebo) enrolled pregnant women, 282 (85%) (140, 83% TDF; 142, 87% placebo) remained in follow-up to 12 months postpartum. Median follow-up was 63 weeks. Time to grade 3/4 or serious adverse event in women was not different by arm (Figure). At scheduled study visits, ALT was >60IU/L for 76 women on 160 occasions in TDF and 86 women on 199 occasions in placebo. Nine women of 155 on TDF and 9 of 157 on placebo had ALT >300IU/L during follow up; with 9 (6%) and 6 (4%), respectively, after study treatment discontinuation (Fisher’s exact p=0.44). All ALT elevations were asymptomatic. Of 323 live births, 286 (89%) (146, 90% TDF; 140, 88% placebo) remained on follow-up until 12 months. One infant died (placebo) shortly after birth with multiple abnormalities. No other deaths occurred. Three infants (all placebo) were HBV infected by 6 months of age. No additional HBV infections were detected between 6 and 12 months. Of 275 infants evaluated for anti-HB antibodies at 12 months, 4 (all placebo) were <10 IU/L; including the 3 with HBV infection and one without HBV infection but a declining antibody level. The proportion of infants experiencing a grade 3/4 or serious adverse event was similar by arm (see Figure). Infants’ weight, height and head circumference Z-scores at 12 months did not differ by arm.
Results were similar to those of the primary 6-month analysis. There were no statistically significant differences between the TDF and placebo arms in infant HBV infection or any secondary safety endpoints up to 12 months postpartum.