User:TechBear/HIV Vaccine Trials Network

The HIV Vaccine Trials Network (HVTN) is a non-profit organization which connects physicians and scientists with activists and community educators for the purpose of conducting clinical trials seeking a safe and effective HIV vaccine. Collaboratively, research professionals and laypeople review potential vaccines for safety, immune response, and efficacy. The HVTN is the only HIV vaccine research network sponsored nationwide by the American government. It also manages the only large-scale HIV vaccine research trial network in Africa.

The HVTN collaborates with the Division of Acquired Immunodeficiency Syndrome (DAIDS). Funding comes from the National Institute of Allergy and Infectious Diseases and National Institutes of Health, which oversee DAIDS. HVTN is headquartered at the Fred Hutchinson Cancer Research Center in Seattle. The vaccines being tested come from various producers, both commercial and non-profit. The HVTN is a network for testing vaccines, and while its members may also work in vaccine development for other entities, the mission of the HVTN does not include vaccine design.

Community involvement
Typically, researchers conduct clinical research on human subjects by asking volunteers to give informed consent to participate in an experiment by taking drugs which no one has demonstrated to be either safe or effective for use. The Nuremberg Code, the Declaration of Helsinki, and the Belmont Report are legal documents written in layman's terms which local governments use to model their laws for establishing rules for conducting clinical trials, and all contemporary clinical trials of international worth follow all the rules set by these precedents.

However, HIV vaccine research requires more than just these protections, and because of this, from the inception of their research the HVTN has instituted a "community advisory board" (CAB) system in addition to the usual controls. The CAB is similar to an Institutional Review Board (IRB) in that the researchers facilitate the granting of public data to both entities, but the difference is that the IRB consists of a professional ethics committee and the CAB consists of any community member who wants to supervise the safety, ethics, efficacy, or any other aspect of the research.

The researchers of the HVTN deemed the creation of the CAB necessary for HIV vaccine research when it has not been necessary for other clinical research because the HIV epidemic is especially urgent, new research techniques are available now that did not exist before recent major advances in genetic engineering, the public is generally overly-willing to volunteer to receive experimental vaccines for this cause, and yet the educational infrastructure already in place to disseminate information about the inherent risk in participating in vaccine research is lacking in society. For too many reasons, there is no precedent for research of this sort on this scale, and without integrating educational programs about this research into existing community institutions, the HVTN simply could not educate people to the required level to make such a fast-moving, expensive, inherently non-commercial research project possible.

African HIV vaccine research trials
In 2003 the HVTN partnered with Harvard University in establishing a small-scale vaccine trials unit in Botswana. A major reason for this project was gathering data about the prevalence of HIV in Africa and assessing the feasibility of getting grassroots support for vaccine trials in non-American culture.

In 2007 HVTN started the first large-scale HIV vaccine trials in Africa, with financial assistance from the SA Aids Vaccine Initiative. These studies will last until 2011 and include up to 3000 participants.

One of those trials begun in 2007, the Phambili Trial, was halted in 2007 due to its similarity to the ineffective vaccine used in the American STEP study.

STEP study
STEP (usually capitalized but not an acronym) is the name for a double-blind randomized controlled trial managed by the HVTN. Candidates for enrollment into the study were men and women identified as high risk candidates for HIV infection but who were currently HIV-negative. It began in 2005 and halted the enrollment of new participants in September 2007 because of potential study-related risk to participants.

The study involved giving participants three vaccinations of adenovirus synthetically modified to contain gag, pol, and nef proteins from HIV. The replication-deficient adenovirus vector carried these HIV-1 genes into the cell. It was hoped that this delivery system would induce a cell-mediated immune response to the modified adenovirus which would both decrease infection and viral set point. Since researchers created synthetic portions of the HIV genome to be ligated into the adenovirus vector, there was no risk of contracting HIV from the vaccine.

In September 2007 researchers stopped the study as a matter of following the protocol when in the entire study, 49 of the 914 men in the vaccine group and 33 men of 922 in the placebo group had tested HIV-positive. The protocol expected that the group which had received the vaccine would have a lower or equal infection rate as compared to the control group, but this was not seen. In fact, certain groups of the vaccine recipients were seen to have higher risk of HIV infection as compared to the placebo group. Merck, the pharmaceutical company which designed the vaccine, closed the study because the vaccine was ineffective, not because it was detrimental. By November 2007 all participants were unblinded when researchers informed them whether they had received the vaccine or placebo.

Researchers stopped a related study in Africa, the Phambili Trial, because it was testing the same vaccine in populations there. While almost everyone enrolled in the STEP study had received the full course of the vaccine, no one in this African trial had been entirely vaccinated.

HVTN 505
On October 1, 2009, the HVTN began a new clinical trial called HVTN 505. HVTN 505 is a project to examine whether a particular DNA prime/boost vaccine regimen will reduce viral load in individuals who later become infected with HIV. The experimental vaccine used in this study was developed by the Vaccine Research Center at the National Institutes of Health (NIH). Study organizers do not expect that this vaccine will prevent HIV infection and thus this vaccine is not planned for licensing, but it is expected to cause a response that will help researchers decide how to direct future vaccine trials.