M.Sc.(Med.), Faculty of Health Sciences, University of the Witwatersrand, 2011 / Hepatitis B virus (HBV) and human immunodeficiency virus (Thakur et al.) are endemic in
South Africa. There no data on the HBV genotypes prevailing in HIV-infected South
Africans. The aim this study was to determine the HBV genotypes in HIV-infected patients
and to identify mutations occurring in the basic core promoter/preccore (BCP/PC) and
complete S regions. Twenty six HBV isolates from HBV-HIV co-infected individuals from
Helen Joseph urban hospital prior to and at six month after initiation of HAART were
analyzed. Three hundred HBV isolates from the rural Shongwe Hospital were recruited prior
to treatment. Restriction fragment length polymorphism (RFLP) together with sequencing of
the BCP/PC and complete surface region amplicons were employed for genotyping and
analysis. There was no significant difference in the HBV genotypes from both cohorts.
Subgenotype A1 was the predominant genotype. HBV DNA was detected in 13/26 (50 %)
Helen Joseph patients and 72/300 (24%) HBV DNA was detected in patients from Shongwe
cohort: 28/300 (9.3%) HBsAg-positive and 44/300 (14.7%) HBsAg-negative. The BCP/PC
region of HBV isolates from both cohorts showed mutations that could account for the
HBeAg negativity, although in the case of the Helen Joseph cohort the HBeAg status was
unknown because of depletion of serum. The HBeAg negativity in 44/49 Shongwe patients
(89,7%) could be accounted for by the following mutations: 1) the basic core promoter
mutations T1753C A1762T G1764A, which down regulate transcription of precore mRNA;
2) the Kozak sequence mutants that affect HBeAg translation, 3) the G1862T mutation,
which interferes with post-translational modification of the HBeAg-precursor, and 4) the
classical G1896A stop codon mutation with C1858T. The G1862T mutation occurred in
HBV from 24.1% HBsAg-positive Shongwe patients but in none of the HBsAg-negative
patients (p<0.05). PreS deletion mutants were found in isolates from both cohorts. These
have previously been described in hepatocellular carcinoma patients. The Helen Joseph HBV isolates had the “a” determinant and immune/vaccine escape mutants. In addition to these,
Shongwe isolates had HBV reactivation markers mutations V168A + S174N in 23.8% of the
HBsAg-negative and in none of the HBsAg-positive infections. Drug resistant mutations
were found in three Shongwe HBV isolates from ART naïve individuals and in none Helen
Joseph HBV isolates. In conclusion, South African HIV-infected individuals were
predominantly infected with subgenotype A1 of HBV. Mutations in the BCP and precore
region of HBV isolates could account for the HBeAg negativity in the majority of patients. A
number of HBV isolates displayed both immune escape and drug resistance mutations that
were responsible of the HBsAg-negativity in patients from which they were isolated.
| Identifer | oai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:wits/oai:wiredspace.wits.ac.za:10539/11176 |
| Date | 26 January 2012 |
| Creators | Makondo, Euphodia |
| Source Sets | South African National ETD Portal |
| Language | English |
| Detected Language | English |
| Type | Thesis |
| Format | application/pdf |
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