ART initiated in second trimester may prevent mother-to-child transmission of HBV
Initiation of combined antiretroviral therapy (ARV) in the second trimester of pregnancy in women co-infected with human immunodeficiency virus (HIV) and hepatitis B virus (HBV) resulted in suppression of viral load at delivery to a level which may prevent mother-to-child transmission (MTCT) of HBV, according to data from the TiP* study presented at the recent APASL 2017 held in Shanghai, China.
Although infant HBV can be prevented by vaccination starting at birth and hepatitis B immunoglobulin (HBIG), 5-15 percent of them remain susceptible to infection whereas HBIG is expensive and often unavailable, according to Dr Athena Kourtis from the National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention in Atlanta, Georgia, US.
“[Therefore,] HBV antiviral therapy during pregnancy has been suggested as an alternative or additional modality to prevent MTCT of HBV,” she said.
The phase II trial randomized 35 pregnant women coinfected with HIV and HBV who were ART-naïve to initiate treatment with either tenofovir (TDF)/lamivudine (3TC)/lopinavir-ritonavir (LPV-r) or zidovudine (ZDV)/3TC/LPV-r from the second trimester (week 14–28) in China. A total of 38 infants were born to the 35 women enrolled, and all infants were vaccinated against HBV and given HBIG within 24 hours of birth. [APASL 2017, abstract LB001]
Compared with the median HBV viral load at baseline (4.01 and 3.64 log10 copies/mL for mothers in the TDF/3TC/LPV-r and ZDV/3TC/LPV-r arms, respectively), all women achieved a reduction in HBV viral load to <6 log10 copies/mL at delivery (1.55 vs 1.40 log10 copies/mL; p=0.25).
Decrease in HBV viral load at delivery was greater in women with baseline viral load of >200,000 IU/mL than those with ≤200,000 IU/mL (decline, -5.55 vs -1.38 log10 copies/mL; p<0.001).
Furthermore, 61 percent of the women achieved HBV DNA suppression to an undetectable level at delivery, with no difference in the proportion of women achieving undetectable HBV DNA at delivery between both treatment arms. There was no transmission of HIV or HBV to the infants observed in all cases.
“[This suggests] that HBV ART in the second trimester may fully prevent HBV MTCT when combined with HBV vaccine and HBIG,” said Kourtis.
Multivariable analysis showed that women with baseline HBV viral load of >200,000 IU/mL (adjusted relative risk [adjRR], 0.12; p=0.03) and hepatitis B e antigen (HBeAg) positive (adjRR, 0.14; p=0.04) were less likely to achieve suppression of viral load to an undetectable level at delivery.
“Pregnant women identified as HBV-infected during their first antenatal visit need to have their HBV DNA or HBeAg status checked; those [with] eAg+ or with high DNA levels may need initiation of HBV ART in the first trimester to reach undetectable HBV DNA levels by delivery … [and] to prevent HBV MTCT,” Kourtis suggested.
None of the women developed resistance to the antiviral drugs during treatment. There were no mutations to TDF, ZDV or LPV/r, and although one woman had 3TC resistance mutations (6SCGA184 and 8ILFM184) at baseline, decrease in hepatitis B viral load still occurred with therapy, according to Kourtis.
Nonetheless, due to the small population size, Kourtis said the study was limited in power to detect differences between the two arms, and to conduct subgroup analyses to explore differences in HBV response in patients with high vs low baseline HBV DNA.