TY - JOUR
T1 - Safety and reactogenicity of canarypox ALVAC-HIV (vCP1521) and HIV-1 gp120 AIDSVAX B/E vaccination in an efficacy trial in Thailand
AU - Pitisuttithum, Punnee
AU - Rerks-Ngarm, Supachai
AU - Bussaratid, Valai
AU - Dhitavat, Jittima
AU - Maekanantawat, Wirach
AU - Pungpak, Swangjai
AU - Suntharasamai, Pravan
AU - Vanijanonta, Sirivan
AU - Nitayapan, Sorachai
AU - Kaewkungwal, Jaranit
AU - Benenson, Michael
AU - Morgan, Patricia
AU - O'Connell, Robert J.
AU - Berenberg, Jeffrey
AU - Gurunathan, Sanjay
AU - Francis, Donald P.
AU - Paris, Robert
AU - Chiu, Joseph
AU - Stablein, Donald
AU - Michael, Nelson L.
AU - Excler, Jean Louis
AU - Robb, Merlin L.
AU - Kim, Jerome H.
N1 - Funding Information:
The protocol was reviewed by the ethics committees of the Ministry of Public Health, the Royal Thai Army, Mahidol University, and the Human Subjects Research Review Board of the U.S. Army Medical Research and Materiel Command. It was also independently reviewed and endorsed by the World Health Organization and the Joint United Nations Program on HIV/AIDS and by the AIDS Vaccine Research Working Group of the National Institute of Allergy and Infectious Diseases at the National Institutes of Health . All participants provided their written informed consent. An independent Data and Safety Monitoring Board conducted periodic reviews for safety, futility, and efficacy.
Funding Information:
We gratefully acknowledge and thank all the participants of the trial and the support rendered by National Institutes of Health, Bethesda, MD, USA; U.S. Military HIV Research Program, Rockville, MD, USA; Department for Disease Control, Bangkok, Thailand; Mahidol University, Bangkok, Thailand, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand; RIMS, Global Solutions for Infectious Diseases, South San Francisco, CA, USA; EMMES Corporation, Rockville MD, USA; Sanofi Pasteur, Swiftwater, PA, USA. We thank Elizabeth Adams, Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, for helpful comments.
PY - 2011/12/21
Y1 - 2011/12/21
N2 - 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.gov NCT00223080
AB - 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.gov NCT00223080
UR - http://www.scopus.com/inward/record.url?scp=83755174375&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0027837
DO - 10.1371/journal.pone.0027837
M3 - Article
C2 - 22205930
AN - SCOPUS:83755174375
SN - 1932-6203
VL - 6
JO - PLoS ONE
JF - PLoS ONE
IS - 12
M1 - e27837
ER -