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.

Integrating reproductive health and HIV indicators into the Nigerian health system--building an evidence base for 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 post-integration. Leveraging resources of HIV programs improved significantly the monitoring of FP-HIV services integration.

The use of routine monitoring and evaluation systems to assess a referral model of family planning and HIV service integration in Nigeria.

OBJECTIVE: To measure changes in service utilization of a model integrating family planning with HIV counselling and testing (HCT), antiretroviral therapy (ART) and prevention of mother-to-child transmission (PMTCT) in the Nigerian public health facilities. DESIGN: It is a retrospective survey of attendance and family planning commodity uptake in 71 health facilities in Nigeria that analyzes the preintegration and postintegration periods between March 2007 and January 2009. METHODS: A prepost retrospective comparison of mean attendance at family planning clinics and couple-years of protection (CYP) compared 6 months preintegration with 9 months postintegration period. An analysis of service ratios was conducted, relating completed referrals at family planning clinics to service utilization at the referring HIV clinics. RESULTS: Mean attendance at family planning clinics increased significantly from 67.6 in preintegration to 87.0 in postintegration. The mean CYP increased significantly from 32.3 preintegration to 38.2 postintegration. Service ratio of referrals from each of the HIV clinics was low but increased in the postintegration period by 4, 34 and 42 per 1000 clients from HCT, ART and PMTCT clinics, respectively. Service ratios were higher in primary healthcare settings than in secondary or tertiary hospitals. Attendance by men at family planning clinics was significantly higher among clients referred from HIV clinics. CONCLUSION: Family planning-HIV integration using the referral model improved family planning service utilization by clients accessing HIV services, but further improvement is possible. Male utilization of family planning services also improved. The government of Nigeria should review the family planning user fee policy and scale up the integration in primary healthcare facilities.

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 x 103 to 1.5 x 108 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.