The preS2/S genes of hepatitis B virus isolated from 29 acutely or chronically infected individuals in the Gauteng province of South Africa were sequenced. Phylogenetic analysis of these sequences in comparison with global isolates from the GenBank database showed that 24 sequences clustered with genotypic group A, three with genotypic group D and one each with genotypic groups B and C. Group A isolates had greater identity with groups D (variation of 6n6 %) and E (6n8 %) than with the Eastern groups B (7n4 %) and C (8n1 %) and were most different from group F (11n0 %). Of the South

Summary Among patients developing viremia on first-line HAART in a South African cohort, 41% resuppressed without regimen switch. At first detection of viremia, 66% had any resistance mutations and 4% had thymidine analogue mutations (TAMs). After 12 months of viremia, 14% had TAMs. Background Episodes of viremia are common in African ART programs. We sought to describe viremia, resuppression, and accumulation of resistance during first-line combination antiretroviral therapy (cART) in South Africa. Methods Retrospective analysis of a cohort receiving zidovudine, lamivudine, and either efavirenz or nevirapine with 6 monthly HIV RNA monitoring. We assessed viremia (HIV RNA >1000 c/mL after initial HIV RNA response) and resuppression (HIV RNA <400 c/mL after viremia). Genotypic resistance testing was performed using stored plasma on a subset at first detection of viremia and subsequently among patients with persistent viremia. Results 3,727 patients initiated cART (median CD4 147 cells/mm3) between 2002 and 2007. Of 1007 patients who developed viremia, 41% (331/815), with subsequent HIV RNA assays, resuppressed without regimen switch. At identification of viremia, 45/68 (66%) had HIV-1 drug resistance; 62% had NNRTI resistance, 37% had M184V/I, and 4% had multi-nucleoside analogue drug mutations. By 12 months of persistent viremia among a subset with resistance testing to 12 months, this increased to 78%, 57%, and 14% respectively. Resistance was associated with a reduced probability of resuppression; however 50% of patients with NNRTI resistance resuppressed while on an NNRTI. Conclusions The majority of patients had NNRTI resistance mutations at detection of viremia. However, 41% resuppressed without regimen switch. Our study supports maximizing first-line use while minimizing risk of significant cross resistance by implementing intensive adherence support and repeat HIV RNA testing 3–6 months after detecting viremia with regimen switch only if viremia persists.

Hepatitis B virus (HBV) was partitioned into type, subtype and isolate categories and the average evolutionary distances within and between categories was plotted at each of 54 points along the genome. The graphs showed alternating variable and conserved domains within and between HBV subtypes and revealed that some specimens assigned to different groups are more similar across several contiguous intervals than specimens belonging to the same group. Isolates were screened individually to determine their conformation to type and mosaic structure was identified in 14/65 specimens. Two entire clades (six specimens) of genotype B had a B/C sequence switch in the core gene region, whereas six genotype D specimens showed D/A switching in one or more regions of the genome. Genotype E was not separate from genotype D in the X and C subgenomic regions. The nature and distribution of polymorphic sites in mosaic regions was mapped at both the nucleotide and protein levels and the position of the variant fragments was related to mutational hot spots and linear epitopes of HBV. Mosaic structure was demonstrated statistically in 11 isolates using bootstrap resampling and recombination, rather than random change, appeared to be the mechanism responsible. The sequence between and including the two DR regions was represented in all putative recombinants. The distribution of genetic distances over subgenomic regions showed that substitution rates are not constant among the lineages of HBV in the preS regions. Genotype F is the most diverse group. Only genotypes A, C and F partition consistently into subtypes.

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The prevalence of hepatitis B surface antigen (HBsAg) was determined in a community-based, cross-sectional, age-stratified sample of children from 0 to 6 years of age (n = 2,299) from the Eastern Cape Province of South Africa. The purpose of the study was to investigate the epidemiology and the age of acquisition of hepatitis B virus (HBV) infection in children, thus providing a preimmunization baseline measure of this infection in the population targeted for HBV immunization in South Africa. Overall, 10.4% (95% CI, 9.2-11.7) of the children tested were HBsAg-positive. There was a high rate of positivity in the 0-6- and 7-12-month age groups at 8.1% (95% CI, 5.5-11.7) and 8.9% (95% CI, 6.1-12.7), respectively, suggesting a higher rate of early acquisition of this infection than previously reported in South Africa. The proportion of HBsAg-positive children increased significantly with increasing age (chi2trend = 5.9, df = 1, P = 0.02), reaching 15.7% in the 61-72-month age group. This is the highest rate of HBV infection reported in community-based children from South Africa, indicating a significant burden of this infection. The difference in HBsAg prevalence between urban and rural children was not statistically significant (chi2 = 0.32, df = 1, P = 0.57). There was also no difference in positivity between males (10.5%; 95% CI, 8.7-12.5) and females (9.8%; 95% CI, 8.1-11.7), (chi2 = 0.006, df = 1, P = 0.94). This study provides the most recent preimmunization, community-based baseline investigation of the epidemiology of HBV infection in children targeted for universal immunization in South Africa.