First Large-Scale HIV Vaccine Trial

[Snowy Owl]

First Large-Scale HIV Vaccine Trial
in South Africa Opens​

http://www3.niaid.nih.gov/news/newsreleases/2007/HVTN503.htm​

A large-scale clinical trial of a candidate HIV vaccine?which previously showed promise in smaller studies in the United States and elsewhere?has now opened in South Africa. The study plans to enroll up to 3,000 HIV-negative men and women, making it the largest African HIV vaccine trial to date.

Conducted jointly by the South African AIDS Vaccine Initiative (SAAVI) and the HIV Vaccine Trials Network (HVTN), the trial is supported by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH). The study vaccine, provided by Merck & Co. Inc. (Whitehouse Station, NJ), contains copies of only three HIV genes, not the entire virus, so it is impossible for a trial volunteer to become infected from the vaccine.

?Our best hope of ending the AIDS epidemic is a safe and effective vaccine,? says NIH Director Elias A. Zerhouni, M.D. ?To achieve that goal requires the concerted effort of governments, scientists and private industry as well as participation by well-informed volunteers.?

?We applaud the South Africans for bringing this important trial to fruition. This international partnership exemplifies the model of collaboration needed to defeat HIV/AIDS,? says NIAID Director Anthony S. Fauci, M.D.

In South Africa the trial is called Phambili (?moving forward?). Also known as HVTN 503, it is a Phase IIb ?test-of-concept? trial, the first such vaccine study in South Africa. This type of trial is designed to provide preliminary information on vaccine efficacy and thus enable researchers to decide whether or not to conduct a larger Phase III efficacy trial that could lead to licensure.

In smaller trials, the vaccine was found to be safe and to stimulate cellular immune responses against HIV in more than half of volunteers. To date, more than 1,800 people have received at least one injection. Two years ago, the first Phase IIb trial of the vaccine opened at sites in the United States, Canada, South America, Australia and the Caribbean (see http://www3.niaid.nih.gov/news/newsreleases/2005/mercktrial.htm), areas where a subtype of HIV called clade B predominates. That trial is ongoing.

As in that study, the main objectives of HVTN 503 are to determine whether the candidate vaccine can prevent HIV infection or, in those who do become infected, lower the level of HIV early on. Additionally, the new trial will determine if the vaccine, which is based on clade B HIV, has the potential to protect against the HIV clade C subtype prevalent in South Africa. Immune responses in the first several hundred volunteers will be assessed to ensure the vaccine induces promising immune responses in this population against the clade C virus before proceeding to full enrollment.

Study volunteers must be healthy, sexually active, HIV-negative men and women, ages 18 to 35 years old. Investigators will assign them at random to receive either the test vaccine or an inactive placebo injection. The trial is double-blind, meaning that neither the researchers nor the volunteers know which a participant has received. All volunteers will be regularly counseled about ways to reduce their risk of acquiring HIV, and they will be given condoms. Access to care and treatment for sexually transmitted infections will be provided, and because recent findings indicate that medical circumcision can reduce the risk of HIV transmission from women to men, access to medical circumcision will also be provided to male participants who desire it.

In South Africa, the trial is led by Glenda Gray, MBBCH, FCPaeds (SA), of the Perinatal HIV Research Unit, University of the Witwatersrand, based at the Chris Hani Baragwanath Hospital in Soweto. James Kublin, M.D., M.P.H., of Fred Hutchinson Cancer Research Center, Seattle, serves as study co-chair. The study is expected to recruit volunteers at five sites in South Africa, located in Soweto, Cape Town, Klerksdorp, Medunsa and Durban.

According to Dr. Gray, the study team has actively sought community endorsement of and support for this clinical trial, both of which are critical to its success. ?Our communities here in South Africa are faced with the burden of HIV on a daily basis, and the trial investigators and study team have spent years developing a rapport with the community so that together we can move forward in our quest to identify improved approaches to prevent new HIV infections.?

The test vaccine contains a weakened adenovirus that serves as a carrier for three clade B HIV genes. Adenoviruses are among the main causes of upper respiratory tract ailments such as the common cold. Because the vaccine contains only three HIV genes housed in weakened adenoviruses, study participants cannot become infected with HIV or get a respiratory infection from the vaccine. The study aims to determine if the HIV genes will induce a cellular immune response, producing immune cells that recognize and kill cells infected with HIV.

The South African Medicines Control Council, the South African Department of Agriculture and the U.S. Food and Drug Administration have reviewed the trial and allowed the study to proceed. In order to conduct the trial, sites also are required to obtain institutional ethics and biosafety committee approvals.

NIAID is a component of the National Institutes of Health. NIAID supports basic and applied research to prevent, diagnose and treat infectious diseases such as HIV/AIDS and other sexually transmitted infections, influenza, tuberculosis, malaria and illness from potential agents of bioterrorism. NIAID also supports research on basic immunology, transplantation and immune-related disorders, including autoimmune diseases, asthma and allergies.

The National Institutes of Health (NIH)?The Nation's Medical Research Agency?includes 27 Institutes and Centers and is a component of the U. S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov

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NIAID-Sponsored Vaccine Trial (HVTN 503) in the Republic of South Africa Questions and Answers

HIV Vaccine Trials Network (HVTN)

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[FrenchieGirl]

Re: First Large-Scale HIV Vaccine Trial

Failure of Vaccine Test Is Setback in AIDS Fight

http://www.nytimes.com/2007/09/22/health/22vaccine.html?hp

By LAWRENCE K. ALTMAN and ANDREW POLLACK
Published: September 22, 2007

A much-heralded H.I.V. vaccine has failed to work in a large clinical trial, dealing another serious setback to efforts to stop the AIDS epidemic.

The vaccine?s developer, Merck, said yesterday that it had halted test vaccinations after the vaccine failed to prevent infection or reduce the severity of infection among volunteers who became infected during the trial.

The trial was closely watched because experts considered the vaccine one of most promising to be tested on people so far.

This was also the first of a new class of H.I.V. vaccine to get this far in clinical trials. The failure of the vaccine raises questions about whether the new approach will work.

?This was viewed as the most promising strategy,? said Dr. Mark B. Feinberg, a vice president of Merck, ?so I think it is a disappointment for us and a disappointment for everyone in the AIDS vaccine area.?

Dr. Feinberg and others said that the failure reinforced the view that H.I.V. is unlike any infection for which scientists have successfully developed a vaccine.

Dr. Anthony S. Fauci, the director of the National Institute of Allergy and Infectious Diseases, which conducted the trial with Merck, said in an interview that ?the results are obviously disappointing.?

But Dr. Fauci also said it was too soon to draw any broad conclusions about the potential of the new class. Merck said it would share its data with scientists.

Health officials deem development of an H.I.V. vaccine the most important tool they need to control the AIDS pandemic, which rivals the worst in history.

The only H.I.V. vaccine to have undergone full-scale testing was based on the traditional approach of stimulating the immune system to produce antibodies against an infectious agent.

Because that vaccine failed, and similar vaccines also failed in earlier stages of testing, many scientists theorized that AIDS might be controlled by stimulating a different component of the immune system, T cells.

They based their reasoning on the observation that among people infected with H.I.V., those who do well tend to have stronger T-cell responses. So, many scientists held out hope that a vaccine that stimulated a strong T-cell response against H.I.V. in advance would help people stave off an infection.

Experiments on animals and smaller tests on people showed enough promise for Merck to develop and conduct the first large tests of that approach, known as cell-mediated immunity.

The vaccine was made from a weakened version of a common cold virus, which served as a way to deliver three synthetically produced genes from the AIDS virus, known as gag, pol and nef. Three doses of the vaccine were injected over six months.

The trial, which began in late 2004, involved 3,000 uninfected volunteers, largely in the United States and Latin America. The trial was the second of the three-stage system that the Food and Drug Administration typically requires before it licenses any vaccine or drug.

Results of the trial were not expected until the end of 2008 at the earliest. But in its first planned interim analysis of 1,500 volunteers, the board monitoring the trial concluded that it was already obvious the vaccine was not working.

?The results were very clear,? said Dr. Feinberg of Merck.

Among 741 people who received at least one dose of the vaccine, 24 cases of infection were found after volunteers had been followed for about 13 months. That compared with 21 infections out of 762 people who received injections of a dummy vaccine.

Nor did the vaccine reduce the amount of H.I.V. in the blood of those who did get infected, which was a second major goal of the study.

The board advised the investigators, led by Dr. Lawrence Corey of the University of Washington and the Fred Hutchinson Cancer Research Center in Seattle, to stop vaccinating volunteers but to continue monitoring them.

Merck is also halting vaccinations in another trial started last year in South Africa.

The latest failure ?is in no way the end of the search for an AIDS vaccine,? the AIDS Vaccine Advocacy Coalition said in a statement.

About 30 other H.I.V. vaccines are being tested in people and all work somewhat differently, said Wayne C. Koff, a senior vice president of the International AIDS Vaccine Initiative in New York.

The National Institute of Allergy and Infectious Diseases, for example, plans to test a vaccine based on genes from the AIDS virus followed with a cold-virus vaccine somewhat similar to Merck?s, Dr. Koff said.

In tests on monkeys, this two-step vaccine showed greater effectiveness than the viral-type vaccine alone, he said.

 

[Gert van der Hoek]

Re: First Large-Scale HIV Vaccine Trial

National Institutes of Health

National Institute of Allergy and Infectious Diseases

Division of Acquired Immune Deficiency Syndrome

AIDS VACCINE RESEARCH WORKING GROUP

Adenoviral Vector Workshop

http://www3.niaid.nih.gov/research/topics/HIV/vaccines/advisory/avrwg/PDF/AVRWGJan07Summary.pdf

 

[Gert van der Hoek]

Re: First Large-Scale HIV Vaccine Trial

Some recent background on the adenovirus 5 based HIV vaccine,

Presentation of Jaap Goudsmit:

http://www.crucell.com/page/downloads/Jaap_Goudsmit_presentation_AMC_28nov07.pdf