Safety and Reactogenicity of Canarypox ALVAC-HIV (vCP1521) and HIV-1 gp120 AIDSVAX B/E Vaccination in an Efficacy Trial in Thailand

A prime-boost vaccination regimen with ALVAC-HIV (vCP1521) administered intramuscularly at 0, 4, 12, and 24 weeks and gp120 AIDSVAX B/E at 12 and 24 weeks demonstrated modest efficacy of 31.2% for prevention of HIV acquisition in HIV-uninfected adults participating in a community-based efficacy trial in Thailand.Reactogenicity was recorded for 3 days following vaccination. Adverse events were monitored every 6 months for 3.5 years, during which pregnancy outcomes were recorded. Of the 16,402 volunteers, 69% of the participants reported an adverse event any time after the first dose. Only 32.9% experienced an AE within 30 days following any vaccination. Overall adverse event rates and attribution of relatedness did not differ between groups. The frequency of serious adverse events was similar in vaccine (14.3%) and placebo (14.9%) recipients (p = 0.33). None of the 160 deaths (85 in vaccine and 75 in placebo recipients, p = 0.43) was assessed as related to vaccine. The most common cause of death was trauma or traffic accident. Approximately 30% of female participants reported a pregnancy during the study. Abnormal pregnancy outcomes were experienced in 17.1% of vaccine and 14.6% (p = 0.13) of placebo recipients. When the conception occurred within 3 months (estimated) of a vaccination, the majority of these abnormal outcomes were spontaneous or elective abortions among 22.2% and 15.3% of vaccine and placebo pregnant recipients, respectively (p = 0.08). Local reactions occurred in 88.0% of vaccine and 61.0% of placebo recipients (p<0.001) and were more frequent after ALVAC-HIV than AIDSVAX B/E vaccination. Systemic reactions were more frequent in vaccine than placebo recipients (77.2% vs. 59.8%, p<0.001). Local and systemic reactions were mostly mild to moderate, resolving within 3 days.The ALVAC-HIV and AIDSVAX B/E vaccine regimen was found to be safe, well tolerated and suitable for potential large-scale use in Thailand.ClinicalTrials.govNCT00223080

Is a HIV vaccine a viable option and at what price? An economic evaluation of adding HIV vaccination into existing prevention programs in Thailand

<p>Abstract</p> <p>Background</p> <p>This study aims to determine the maximum price at which HIV vaccination is cost-effective in the Thai healthcare setting. It also aims to identify the relative importance of vaccine characteristics and risk behavior changes among vaccine recipients to determine how they affect this cost-effectiveness.</p> <p>Methods</p> <p>A semi-Markov model was developed to estimate the costs and health outcomes of HIV prevention programs combined with HIV vaccination in comparison to the existing HIV prevention programs without vaccination. The estimation was based on a lifetime horizon period (99 years) and used the government perspective. The analysis focused on both the general population and specific high-risk population groups. The maximum price of cost-effective vaccination was defined by using threshold analysis; one-way and probabilistic sensitivity analyses were performed. The study employed an expected value of perfect information (EVPI) analysis to determine the relative importance of parameters and to prioritize future studies.</p> <p>Results</p> <p>The most expensive HIV vaccination which is cost-effective when given to the general population was 12,000 Thai baht (US$1 = 34 Thai baht in 2009). This vaccination came with 70% vaccine efficacy and lifetime protection as long as risk behavior was unchanged post-vaccination. The vaccine would be considered cost-ineffective at any price if it demonstrated low efficacy (30%) and if post-vaccination risk behavior increased by 10% or more, especially among the high-risk population groups. The incremental cost-effectiveness ratios were the most sensitive to change in post-vaccination risk behavior, followed by vaccine efficacy and duration of protection. The EVPI indicated the need to quantify vaccine efficacy, changed post-vaccination risk behavior, and the costs of vaccination programs.</p> <p>Conclusions</p> <p>The approach used in this study differentiated it from other economic evaluations and can be applied for the economic evaluation of other health interventions not available in healthcare systems. This study is important not only for researchers conducting future HIV vaccine research but also for policy decision makers who, in the future, will consider vaccine adoption.</p

Cytoadherence and ultrastructure of Plasmodium falciparum-infected erythrocytes from a splenectomized patient

In malarial infections of primates, the spleen has been shown to modulate parasite antigen expression on the surfaces of infected erythrocytes. The processes affected include cytoadherence, which is central to the pathophysiology of severe falciparum malaria, and the related phenomenon of rosette formation. In this study, the cytoadherence and rosette formation behaviors of Plasmodium falciparum-infected erythrocytes from a splenectomized patient were examined during the first erythrocytic cycle in vitro. Ultrastructural studies were also performed. Infected erythrocytes were found to cytoadhere to C32 melanoma cells via leukocyte differentiation antigen CD36 but not intercellular adhesion molecule 1. They also displayed on their surfaces electron-dense knobs similar in structure and density to those on infected erythrocytes from intact hosts. These findings may reflect a stable cytoadherent phenotype of the parasite isolate that is unaffected by the absence of the spleen. Alternatively, the modulating role of the spleen may have been assumed by other organs of the mononuclear phagocytic system in a previously infected individual. No rosette formation was observed, but as not all natural isolates form rosettes, this observation may or may not be related to the asplenic status of the patient. Parasite and host factors appear to be important in determining the effect of splenectomy on cytoadherence and rosette formation in human falciparum malaria.</jats:p