Partially Randomized, Non-Blinded Trial of DNA and MVA Therapeutic Vaccines Based on Hepatitis B Virus Surface Protein for Chronic HBV Infection

BACKGROUND: Chronic HBV infects 350 million people causing cancer and liver failure. We aimed to assess the safety and efficacy of plasmid DNA (pSG2.HBs) vaccine, followed by recombinant modified vaccinia virus Ankara (MVA.HBs), encoding the surface antigen of HBV as therapy for chronic HBV. A secondary goal was to characterize the immune responses. METHODS: Firstly 32 HBV e antigen negative (eAg(-)) participants were randomly assigned to one of four groups: to receive vaccines alone, lamivudine (3TC) alone, both, or neither. Later 16 eAg(+) volunteers in two groups received either 3TC alone or both 3TC and vaccines. Finally, 12 eAg(-) and 12 eAg(+) subjects were enrolled into higher-dose treatment groups. Healthy but chronically HBV-infected males between the ages of 15-25 who lived in the western part of The Gambia were eligible. Participants in some groups received 1 mg or 2 mg of pSG2.HBs intramuscularly twice followed by 5×10(7) pfu or 1.5×10(8) pfu of MVA.HBs intradermally at 3-weekly intervals with or without concomitant 3TC for 11-14 weeks. Intradermal rabies vaccine was administered to a negative control group. Safety was assessed clinically and biochemically. The primary measure of efficacy was a quantitative PCR assay of plasma HBV. Immunity was assessed by IFN-γ ELISpot and intracellular cytokine staining. RESULTS: Mild local and systemic adverse events were observed following the vaccines. A small shiny scar was observed in some cases after MVA.HBs. There were no significant changes in AST or ALT. HBeAg was lost in one participant in the higher-dose group. As expected, the 3TC therapy reduced viraemia levels during therapy, but the prime-boost vaccine regimen did not reduce the viraemia. The immune responses were variable. The majority of IFN-γ was made by antigen non-specific CD16(+) cells (both CD3(+) and CD3(-)). CONCLUSIONS: The vaccines were well tolerated but did not control HBV infection. TRIAL REGISTRATION: ISRCTN ISRCTN67270384

Application of real-time PCR to quantify hepatitis B virus DNA in chronic carriers in The Gambia

BACKGROUND/AIM: The study aimed at developing a real-time quantitative PCR assay to monitor HBV serum virus load of chronic carriers enrolled in therapeutic trials. METHOD: Quantitative real-time PCR assay was carried out using SYBR-Green signal detection and primers specific to the S gene. Thermal cycling was performed in an ABi 5700 sequence detection system. The assay was calibrated against an international HBV DNA standard and inter- and intra-assay reproducibility determined. Levels of viral load were monitored for 1-year in lamivudine treated carriers. Correlation between HBV DNA levels and HBeAg sero-status was determined in untreated carriers. RESULTS: The qPCR assay showed good intra- and inter-assay reproducibility over a wide dynamic range (1.5 × 10(3 )to 1.5 × 10(8 )copies/mL) and correlated well with those from a commercial assay (r = 0.91, (p < 0.001). Viral load levels dropped dramatically but temporarily during and after a short course of lamivudine therapy. HBV DNA was a more reliable indicator of the presence of virus than HBe antigen and was detected in 77.0% (161/209) of HBeAg negative and in all HBeAg positive carriers. CONCLUSION: This method is reliable, accurate, and reproducible. HBV DNA Quantification by qPCR can be used to monitor the efficacy of HBV therapy and useful in understanding the natural history of HBV in an endemic area

Integration de la sante de la reproduction et les indices du vih dans le systeme de la sante publique: L’etablissement d’une base d’evidence pour l’action

The lack of integrated M&E system makes it difficult to assess the effectiveness of HIV and family planning (FP) service integration. Since 2007, Nigeria integrated FP and HIV M&E systems. A pre-post survey compared the availability and use of FP-HIV integration M&E tools six months pre- and 12-months post-integration in 71 health facilities supported by the Global HIV/AIDS Initiative Nigeria (GHAIN). Pre-integration, four facilities (6%) had national FP registers, 32 (45%) had monthly aggregated FP data and 33 (46%) reported data up to national level. Post-integration, all (100%) facilities used national FP register with FP-HIV integration indicators, and reported data up to national level. Sixty six facilities (93%) had at least one monthly supervisory visit. Average number of FP clients per facility referred for HIV testing increased from five in the first month to 15 by month 12 postintegration. Leveraging resources of HIV programs improved significantly the monitoring of FP-HIV services integration (Afr J Reprod Health 2010; 14[1]:109-116).Le manque de système de la S & E intègre, le rend difficile à évaluer l’efficacité de l’intégration du service du VIH et de la planification familiale (PF) Depuis 2007, le Nigéria a intégré la PF et le les systèmes de surveillance et d’évaluation (S & E). Une enquête faite avant et après l’intégration a comparé la disponibilité et l’emploi des outils de l’intégration de la S & E et de la PF – VIH six mois avant et 12 mois après l’intégration dans 71 établissements de santé soutenus par Global HIV/AIDS Initiative Nigéria (GHAIN). En ce qui concerne pre-intégration, quatre établissements (6%) avaient des registres de la PF nationale, 32 (45%) avaient des données mensuelles totales de la PF et 33 (46%) ont signalé les données jusqu’au niveau national. Pour ce qui est de la post-intégration, tous les établissements (100%) se sont servis du registre de la PF nationale avec les indices de l’intégration PF – VIH et ont signalé les données jusqu’au niveau national. Soixante-six établissements (93%) avaient au moins une visite de surveillance par mois. Le nombre moyen des clients de la PF dans chaque établissement qui ont été orientes vers des établissements pour le test pour le VIH a augmente de 5 le premier mois jusq’au 15 dans le 12ième mois de la post intégration. Les ressources destinées aux programmes du VIH ont amélioré de manière importante les services de la moniteur et de la PF – VIH intégration (Afr J Reprod Health 2010; 14[1]:109-116)