STD Quarterly: HIV vaccine update: Progress made, but more work is left to do in research
STD Quarterly
HIV vaccine update: Progress made, but more work is left to do in research
Encouraging news comes from the HIV vaccine research front, where an investigational vaccine regimen tested in a Thailand clinical trial has been shown to be well tolerated and to have a modest effect in preventing HIV infection.1-3
The Thai Phase III HIV vaccine study, also known as RV144, was designed to test the safety and effectiveness of a prime-boost regimen of two vaccines: ALVAC-HIV vaccine, which is a modified canarypox vaccine developed by Lyon, France-based Sanofi Pasteur, and AIDSVAX B/E vaccine, which is a glycoprotein 120 vaccine initially developed by Vaxgen and now licensed to the San Francisco-based Global Solutions for Infectious Diseases. The two vaccines are based on the subtype B and E HIV strains that commonly circulate in Thailand.
The trial, which opened in October 2003, enrolled 16,402 men and women ages 18-30. Study participants received the ALVAC HIV vaccine or placebo at enrollment and again after one, three, and six months. The AIDSVAX B/E vaccine or placebo was given to participants at three and six months. Participants were tested for HIV infection every six months for three years and were counseled on how to avoid becoming infected with HIV during each clinic visit.
An analysis of the findings indicates 74 of 8,198 placebo recipients became infected with HIV compared with 51 of 8,197 participants who received the vaccine regimen. This level of effectiveness in preventing HIV infection was found to be statistically significant. However, the vaccine regimen had no effect on the amount of virus in the blood of volunteers who acquired HIV infection during the study, scientists report.
"The Thai study demonstrates why the HIV vaccine field must take a balanced approach to conducting both the basic research needed to discover and design new HIV vaccines and, when appropriate, testing candidate vaccines in people," says Margaret Johnston, PhD, director of the Vaccine Research Program within the National Institute of Allergy and Infectious Diseases' (NIAID) Division of AIDS. "Both avenues provide critical information that will continue to help us better understand what is needed to develop a fully protective HIV vaccine."
Scientists say more information will come with the extended results of the follow-on study, RV152, due in 2013. The prospective cohort study will examine the virological, immunological, and clinical course of the HIV-infected vaccinees.4
Scientists with the RV144 study had hypothesized that the vaccine would reduce HIV acquisition by 50%. The study results were statistically significant, although they did not reach the level that had been specified, says Larry Corey, MD, co-director of the Vaccine and Infectious Disease Institute at Fred Hutchinson Cancer Research Center and the principal investigator of the HIV Vaccine Trials Network (HVTN), both based in Seattle.
"While these results are not at the level we will need to effectively control the AIDS pandemic, it is an indication that scientists will reach the goal of developing an effective HIV vaccine," says Corey. "There are several other vaccine candidates in the research pipeline and today's encouraging results will provide renewed enthusiasm for human clinical trials, as well as additional HIV vaccine discovery."
Advancing research into Phase III testing has been a daunting prospect for researchers. HVTN does not have any Phase III trials at this time, says Sarah Alexander, organization spokeswoman.Two trials, HVTN 502 (also known as the Step Study) and HVTN 503 (Phambili) were Phase 2B test of concept trials. Both were stopped in 2007 after an analysis of the Step Study indicated that the study would not be able to achieve positive results, she notes.
HVTN is moving forward in vaccine development, as enrollment has begun in an exploratory HIV vaccine clinical study that will examine whether a two-part vaccine regimen can decrease viral load in study participants who later become infected with HIV. The study is enrolling men who have sex with men. Pending final site approvals, the study will be conducted in Atlanta; Bethesda, MD; Birmingham, AL; Boston; Chicago; Los Angeles; Nashville; New York City; Philadelphia; Rochester; San Francisco; and Seattle. (Editor's note: For more information on enrollment, visit the study's web site, www.Hopetakesaction.org.)
HVTN 505 is a Phase II, randomized, placebo-controlled, double-blind clinical trial. It employs a prime-boost strategy of two investigational vaccines developed by scientists at NIAID's Vaccine Research Center: a series of three immunizations with recombinant DNA-based vaccine over eight weeks, followed by one shot of a recombinant vaccine based on a weakened adenovirus Type 5 that carries the vaccine contents and helps stimulate the immune system. Of the 1,350 participants slated for enrollment, half will receive the investigational vaccine regimen, and half will receive placebo injections.
As an exploratory study, HVTN 505 is not part of a typical product development path of studies that leads to vaccine licensure; rather, it serves as the basis for subsequent research that will build upon its findings, explain HVTN officials.
Why test an HIV vaccine that is not intended or expected to prevent HIV infection? As the NIAID explains in a question and answer sheet: "A vaccine that reduces viral load in people infected with HIV would be a significant scientific breakthrough. Reducing viral load is important because typically people infected with HIV who have lower viral loads take longer to become sick and develop symptoms of AIDS. People with reduced levels of virus may also have a diminished ability to transmit the virus to others. Therefore, an HIV vaccine that reduces viral load may benefit a vaccinated individual who later becomes infected with HIV by delaying the onset of illness and the lifetime need for antiretroviral medicines. It may also benefit the public health by reducing HIV transmission to uninfected people."5
References
- Rerks-Ngarm S. Phase III trial of HIV prime-boost vaccine combination in Thailand: Result of final analysis. Presented at the AIDS Vaccine Conference 2009. Paris; October 2009.
- Kim J. Post-infection cellular immune responses in recipients following ALVAC-HIV + AISDVax B/E prime-boost vaccination in the Thai Phase III trial. Presented at the AIDS Vaccine Conference 2009. Paris; October 2009.
- De Souza M. Immunogenicity of ALVAC-HIV® (vCP1521) and AIDSVAX® B/E prime boost vaccination in RV144, the Thai Phase III HIV vaccine trial. Presented at the AIDS Vaccine Conference 2009. Paris; October 2009.
- A (prime) boost for HIV vaccine research? Lancet 2009; 374:1,119.
- National Institute of Allergy and Infectious Diseases. Questions and answers. The HVTN 505 HIV vaccine regimen study. Fact sheet. Accessed at www3.niaid.nih.gov/NIAID.
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