Biomedical interventions: vaccines
Vaccination with ALVAC and AIDSVAX to Prevent HIV-1 Infection in Thailand.
Supachai Rerks-Ngarm, M.D., Punnee Pitisuttithum, M.D., D.T.M.H., Sorachai Nitayaphan, M.D., Ph.D., Jaranit Kaewkungwal, Ph.D., Joseph Chiu, M.D., Robert Paris, M.D., Nakorn Premsri, M.D., Chawetsan Namwat, M.D., Mark de Souza, Ph.D., Elizabeth Adams, M.D., Michael Benenson, M.D., Sanjay Gurunathan, M.D., Jim Tartaglia, Ph.D., John G. McNeil, M.D., Donald P. Francis, M.D., D.Sc., Donald Stablein, Ph.D., Deborah L. Birx, M.D., Supamit Chunsuttiwat, M.D., Chirasak Khamboonruang, M.D., Prasert Thongcharoen, M.D., Ph.D., Merlin L. Robb, M.D., Nelson L. Michael, M.D., Ph.D., Prayura Kunasol, M.D., Jerome H. Kim, M.D., for the MOPH–TAVEG Investigators. 2009 New England Journal of Medicine. Epub Ahead of print October 20, 2009 (10.1056/NEJMoa0908492)
The development of a safe and effective vaccine against the human immunodeficiency virus type 1 (HIV-1) is critical to pandemic control. In a community-based, randomized, multicenter, double-blind, placebo-controlled efficacy trial, the authors evaluated four priming injections of a recombinant canarypox vector vaccine (ALVAC-HIV [vCP1521]) plus two booster injections of a recombinant glycoprotein 120 subunit vaccine (AIDSVAX B/E). The vaccine and placebo injections were administered to 16,402 healthy men and women between the ages of 18 and 30 years in Rayong and Chon Buri provinces in Thailand. The volunteers, primarily at heterosexual risk for HIV infection, were monitored for the coprimary end points: HIV-1 infection and early HIV-1 viraemia, at the end of the 6-month vaccination series and every 6 months thereafter for 3 years. In the intention-to-treat analysis involving 16,402 subjects, there was a trend toward the prevention of HIV-1 infection among the vaccine recipients, with a vaccine efficacy of 26.4% (95% confidence interval [CI], –4.0 to 47.9; P=0.08). In the per-protocol analysis involving 12,452 subjects, the vaccine efficacy was 26.2% (95% CI, –13.3 to 51.9; P=0.16). In the modified intention-to-treat analysis involving 16,395 subjects (with the exclusion of 7 subjects who were found to have had HIV-1 infection at baseline), the vaccine efficacy was 31.2% (95% CI, 1.1 to 51.2; P=0.04). Vaccination did not affect the degree of viraemia or the CD4+ T-cell count in subjects in whom HIV-1 infection was subsequently diagnosed. This ALVAC-HIV and AIDSVAX B/E vaccine regimen may reduce the risk of HIV infection in a community-based population with largely heterosexual risk. Vaccination did not affect the viral load or CD4+ count in subjects with HIV infection. Although the results show only a modest benefit, they offer insight for future research.
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Editors’ note: These encouraging results are sparking HIV vaccine scientists to explore how this prime-boost strategy using vaccines that were adapted to circulating Thai subtypes (B and E) provided modest levels of protection. This paper was published on line October 20 th simultaneously with the plenary presentation of the results at the AIDS Vaccine 2009 conference in Paris. Webcasting of the conference sessions and media conferences, including the RV144 media conference, is available to viewers until January 21, 2010 at 12:00 PM Central European Time at: http://www.hivvaccineenterprise.org/conference/2009/webcasting.html The mITT or modified intent-to-treat analysis is the gold standard analysis that was followed by the trial’s Data Safety Monitoring Board throughout this test-of-concept trial. It includes all trial participants randomised in the trial with the exception of 7 who were already HIV infected at their first post-screening study visit before the first shot. How exactly did this strategy work (what are the immune correlates of protection?), how high did vaccine efficacy go in the first year and how much did it decrease after the first year post-vaccination (would booster doses be needed?), does the vaccine work better in those at lower risk of infection (why and what would that mean for future vaccine trial design?), was it a single vaccine or the prime-boost combination that produced protective immune responses, was matching the vaccines to Thai virus subtypes important to vaccine efficacy in this study population, and are there different immune system responses to prevent HIV infection compared to those that attempt to control it after infection is established? These and many other intriguing questions are opening up avenues for exploration and invigorating us all. An HIV vaccine is many years away but now we know that it will come.
Potential population health outcomes and expenditures of HIV vaccination strategies in the United States.
Long EF, Brandeau ML, Owens DK. Vaccine. 2009; 27(5402-5010).
Estimating the potential health benefits and expenditures of a partially effective HIV vaccine is an important consideration in the debate about whether HIV vaccine research should continue. We developed an epidemic model to estimate HIV prevalence, new infections, and the cost-effectiveness of vaccination strategies in the U.S. Vaccines with modest efficacy could prevent 300,000-700,000 HIV infections and save $30 billion in healthcare expenditures over 20 years. Targeted vaccination of high-risk individuals is economically efficient, but difficulty in reaching these groups may mitigate these benefits. Universal vaccination is cost-effective for vaccines with 50% efficacy and price similar to other infectious disease vaccines.
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