Event rate differences greater than 3% can be detected with >90% power when the true rates are near 50%

Event rate differences greater than 3% can be detected with >90% power when the true rates are near 50%. == Randomization and Blinding == Randomization used centrally (EMMES Corporation) generated permuted blocks of random sizes for a set of coded treatment labels that coincided with coded treatment stocks. The frequency of serious adverse events was similar TRAILR3 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 Bleomycin 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. == Conclusions/Significance == 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. == Trial Registration == ClinicalTrials.govNCT00223080 == Introduction == HIV/AIDS has emerged as a worldwide public health threat and is associated with high morbidity and mortality. Worldwide, the total number of people living with HIV in 2009 2009 was estimated to be 33.3 million with 2.6 million being newly infected[1]. In Thailand, 14,000 new HIV infections occur each year despite the considerable efforts and success in controlling the HIV epidemic[2],[3]. The circulating recombinant form CRF01_AE and subtype B dominate the HIV epidemic in Thailand[4],[5]. The development of a safe, effective, easily administered and inexpensive AIDS vaccine is desperately needed worldwide, and the Thai Ministry of Public Health has long recognized that need and has strongly supported HIV vaccine research in Thailand[6],[7]. An AIDS vaccine as part of a comprehensive prevention package is considered the best long-term solution in controlling the HIV/AIDS pandemic[8],[9]. Safety is a paramount consideration for all preventive vaccines. Monitoring and assessing vaccine safety is a priority for public health. It is generally thought that such interventions must have modest rates of reactions and only rare severe or serious events associated with their use[10],[11]. This prime-boost concept applied to AIDS vaccines employs viral vector prime together with a soluble envelope subunit boost. The concept is aimed specifically at inducing both CD4+ and CD8+ T-cell as well as binding and neutralizing antibody immune responses[12][15]. An effective immune response will likely comprise a combination of antibodies and CD4+ and CD8+ T cells that recognize, neutralize and/or destroy diverse strains of HIV before an infection becomes irreversibly established[16]. Given the hurdles of eliciting broadly neutralizing antibodies, the focus of HIV vaccine development in recent years turned to evaluating vaccines capable of reducing viral replication after infection (T-cell vaccines)[17],[18]. Although contradicted by some studies[19], control of viral replication could conceivably slow the rate of disease progression as suggested by non-human primate (NHP) challenge studies[20][23]and/or reduce transmission of HIV from infected vaccine recipient to partner[24]. Earlier HIV vaccine trials from 19942000 tested recombinant protein candidate vaccines that were capable of inducing antibody responses[25]. One of these, a bivalent recombinant gp120 (AIDSVAX B/E) derived from HIV-1 CRF01_AE and B subtypes was tested in Phase I/II trials and was shown to be safe and immunogenic[26],[27]. A Phase Bleomycin III trial using AIDSVAX B/E in Thai injecting drug users, while confirming safety, did not provide evidence of protection against HIV acquisition. In addition, a concurrent Phase III trial using a bivalent gp120 subtype B vaccine (AIDSVAX B/B), among North American and European men who have sex with Bleomycin men and women at high risk for heterosexual transmission of HIV, did not protect against HIV infection[28],[29]. Attenuated non-replicating poxvirus vectors, in particular canarypox (ALVAC) vectors, have been extensively studied and appeared to be safe in phase I and II clinical studies[30]. ALVAC prime.