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 3,312 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.

Mother-to-child transmission of hepatitis B virus: Evolution of hepatocellular carcinoma-related viral mutations in the post-immunization era

“…In this study, we found that maternal HBeAg positivity and HBV DNA >10 6 copies/mL contributed significantly to the trans-placental transmission, which is quite consistent with the risk of failure to the immunoprophylaxis [23][24][25][26][27]. The trans-placental transmission was more frequent in the mothers with genotype B2 and those younger than 27 years, possibly because of their higher viral load and/or HBeAg positivity.…”

“…Antiviral treatment at the late stage of pregnancy has been proven to be effective in reducing HBV MTCT [28]. Our data, together with others' [23][24][25][26][27], are important in identifying the HBsAg-positive mothers who are more likely to develop MTCT and need antiviral treatment at the late stage of pregnancy.…”

Early childhood transmission of hepatitis B prior to the first hepatitis B vaccine dose is rare among babies born to HIV-infected and non-HIV infected mothers in Gulu, Uganda

“…Similar to many SSA countries, Uganda's expanded program on immunization (UNEPI) integrated the HBV vaccination in its schedule in 2002 [11] with the first vaccine dose included in a pentavalent vaccine given at the age of six weeks and the second and third dose at 10 and 14 weeks respectively [12]. Currently, the HepB3 coverage in Uganda is about 78% [13].…”

Development and validation of an oligonucleotide ligation assay to detect lamivudine resistance in hepatitis B virus

“…The OLA was evaluated by testing plasma from individuals known to be chronically HBV infected and treated with 3TC for 1–8.5 years who were enrolled in the multicenter HIV Prevention and Treatment cohort (ClinicalTrials.gov NCT00433030) in Thailand (Khamduang et al, 2013, 2012). DNA was extracted from participants’ plasma using an automatic sample extraction system (Abbott M2000sp).…”

“…OLA probes to detect mutations encoding rtL180M and rtM204V/I were designed to accommodate common genetic variations using alignments of HBV sequences from subjects residing in Thailand (Khamduang et al, 2013, 2012) (Table 1). Wild-type and mutant plasmids, generated by cloning subjects’ amplicons (TOPO ® TA Cloning ® Kit for Sequencing, Invitrogen, Carlsbad, CA), were mixed at 2, 5, 10, 25, 50, 75, 90, and 95% mutant, and used to quantify the proportion of mutants in the clinical specimens.…”