Analysis of residual perinatal transmission of hepatitis B virus (HBV) and of genetic variants in human immunodeficiency virus and HBV co-infected women and their offspring

Abstract

Background: Despite implementation of universal infant hepatitis B (HB) vaccination, mother-to-child transmission (MTCT) of hepatitis B virus (HBV) still occurs. Limited data are available on the residual MTCT of HBV in human immunodeficiency virus (HIV)-HBV co-infected women.

Objectives: We assessed the prevalence of HBV infection among HIV-infected pregnant women and the rate of residual MTCT of HBV from HIV-HBV co-infected women and analyzed the viral determinants in mothers and their HBV-infected children.

Study design: HIV-1 infected pregnant women enrolled in two nationwide perinatal HIV prevention trials in Thailand were screened for HB surface antigen (HBsAg) and tested for HBeAg and HBV DNA load. Infants born to HBsAg-positive women had HBsAg and HBV DNA tested at 4-6 months. HBV diversity within each HBV-infected mother-infant pair was analyzed by direct sequencing of amplified HBsAg-encoding gene and cloning of amplified products.

Results: Among 3312 HIV-1 infected pregnant women, 245 (7.4%) were HBsAg-positive, of whom 125 were HBeAg-positive. Of 230 evaluable infants born to HBsAg-positive women, 11 (4.8%) were found HBsAg and HBV DNA positive at 4-6 months; 8 were born to HBeAg-positive mothers. HBV genetic analysis was performed in 9 mother-infant pairs and showed that 5 infants were infected with maternal HBV variants harboring mutations within the HBsAg "a" determinant, and four were infected with wild-type HBV present in highly viremic mothers.

Conclusions: HBV-MTCT still occurs when women have high HBV DNA load and/or are infected with HBV variants. Additional interventions targeting highly viremic women are thus needed to reduce further HBV-MTCT.

Keywords: 95% confidence interval; 95%CI; DNA; EPI; HB; HBIg; HBV; HBeAg; HBs antigen variants; HBsAg; HIV; HIV pregnant women; Hepatitis B vaccine failure; IQR; MTCT; Mother-to-child transmission; PCR; Thailand; deoxyribonucleic acid; expanded program on immunization; hepatitis B; hepatitis B immune globulin; hepatitis B virus; human immunodeficiency virus; interquartile range; mother-to-child transmission; polymerase chain reaction; the surface antigen of the hepatitis B virus; the “e” antigen of the hepatitis B virus.

Figure 1

Association between the level of plasma HBV DNA and HBeAg status in HBV-HIV co-infected mothers.

Figure 2

Overall study diagram

Figure 3

Evolution of HBV quasispecies in 9 transmitting mother-child pairs. M indicates the maternal sample. I0, I4 and I6 indicate infant samples at birth, 4 and 6 months, respectively. Figures directly above each bar indicate the number of clones analyzed. The patient identifier is given beside the panel label. Wild type is indicated in blue, variants are indicated by other colors. Three possible patterns of HBV mother-to-child transmission were observed:1) Transmission of wild-type variants from mothers with high level of HBV DNA (A, B, C, D), 2) Transmission of maternal minor variants to their infants (E, F), and 3) Transmission of HBV variants already existing in mothers (G, H, I).