Safety and reactogenicity of canarypox ALVAC-HIV (vCP1521) and HIV-1 gp120 AIDSVAX B/E vaccination in an efficacy trial in Thailand

Abstract

Background: 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.

Methodology/principal findings: 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.

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.

Conflict of interest statement

Competing Interests: Sanjay Gurunathan reports being employee of Sanofi Pasteur, who provided the reagents for the ALVAC-HIV vaccine. Donald P. Francis is employee of Global Solutions for Infectious Diseases (VaxGen), who provided the reagents for the immunogenicity assays. No other potential conflict of interest relevant to this article was reported. The views expressed are those of the authors and should not be construed to represent the positions of the U.S. Army or Department of Defense or other institutions involved in the study. Donald Stablein is employee of The EMMES Corporation, a Contract Research Organization (CRO), responsible for the statistical analysis of the clinical trial data. This does not alter the authors' adherence to all the PLoS ONE policies on sharing data and materials.

Figures

Figure 1. Percentage of individuals with local and systemic reactions by treatment and dose administered.

Local reactions were separately recorded for each of the ALVAC-HIV or placebo and AIDSVAX B/E or placebo injections since they were administered in separate arms. Systemic reactions following the third and fourth vaccinations could not be attributed to the ALVAC-HIV or AIDSVAX B/E separately as both were administered simultaneously, although in two different arms. Severe (dark grey), moderate (mild grey) and mild (light grey).