Thai RV144 Phase III HIV Vaccine Trial

[J220]

Interesting, I had no idea the good ol' US Army was carrying out HIV vaccine trials. At least we should know the results of this by '09, only a year and a half away.

This is from http://www.sciencedaily.com/upi/index.php?feed=Science&article=UPI-1-20070720-12575200-bc-us-hivvaccinetrial.xml



U.S. study of HIV vaccine cleared by board

FREDERICK, Md., July 20 (UPI) -- The U.S. Army Surgeon General was told this week by an independent board that its study in Thailand into a possible HIV vaccine can resume.

A U.S. Army news release said Thursday that the military-sponsored Phase III Prime Boost HIV Vaccine trial will continue after the Data Safety and Monitoring Board cleared it for additional research.

The board's inquiry into the medical trials found that there were no significant medical concerns present worthy of ending the research.

While the board found that the current level of research in the trial doesn't suggest a vaccine is imminent, it did rule that the trial would ultimately provide a definitive answer on the matter.

The U.S. Army said the trial is expected to conclude in 2009 and thanked the 16,402 Thai citizens taking part in the endeavor.

[J220]

Some more onfo on this vaccine at http://www.primeboost3.org/press_eng_bk.htm


Phase III Prime-Boost HIV Vaccine Efficacy Trial in Thailand

Trial Objectives

The primary objective of the trial is to see whether a two-pronged HIV vaccine strategy, ALVAC-HIV (vCP1521) boosted with AIDSVAX B/E gp120, will protect Thai volunteers from HIV infection. The trial is designed to detect a 50 percent reduction in the incidence of HIV infection among vaccines over a three-year period.

A secondary objective is to determine the effect of immunization in controlling viremia and maintaining CD4+ counts should a volunteer become infected with HIV by engaging in risky behavior while in the trial. Both are felt to be indicators of long-term control of disease.

Safety Profile and Composition of the Vaccines

Both vaccines have been studied in thousands of volunteers throughout the world and have excellent safety profiles. It is impossible to get HIV from either vaccine.

ALVAC-HIV (vCP1521) is a live recombinant canarypox vector into which selected HIV genes are inserted. Because canarypox can neither cause disease in humans, nor integrate into the genome, it is attractive as an AIDS vaccine technology. The vaccine targets HIV subtype E, which is most prevalent in Thailand, and will act as the “prime” to the immune system in the study. The canarypox stimulates cellular immunity, by activating cytotoxic T lymphocytes (CTLs), which recognize and kill cells infected with HIV.

VaxGen gp120 B/E (AIDSVAX B/E) is made from a synthetic clone of gp120, a protein found on the surface of HIV. It contains no genetic material. Using recombinant DNA technology, the gene for gp120 is cloned and then duplicated by Chinese hamster ovary cells in commercial-scale fermenters. The gp120 is then purified and mixed with alum, an adjuvant that intensifies the immune response. It too has been designed to target HIV subtype E. AIDSVAX stimulates the humoral immune response, as measured by antibody production.

The hope is that stimulating both arms of the immune system – cellular and humoral – will result in protection against infected cells and freely circulating virus.


Trial Design

The protocol calls for enrolling 16,000 HIV-uninfected volunteers between the ages of 20 and 30 years from Chon Buri and Rayong provinces, in the Eastern Seaboard region of the country. Half the trial participants will receive a dose of ALVAC-HIV (vCP1521) at 0, 1, 3 and 6 months as the “prime” along with a dose of AIDSVAX B/E at 3 and 6 months as the “boost.” The other half of the volunteers will receive placebo injections at all four vaccination visits.

The trial is expected to take two years to enroll. All volunteers will receive individual, extensive counseling on HIV risk reduction. The immunization phase will take six months, with follow-up for three years thereafter. After the vaccination phase, the volunteers will have their blood drawn routinely every six months, to determine whether or not they have become infected with HIV as a result of engaging in risky behavior. All volunteers acquiring HIV infection during the trial will continue to be followed in the study for evidence of continued vaccine safety, and will be treated for HIV according to Thailand national guidelines which include provision of highly active anti-retroviral drug therapy. The trial is expected to conclude in 2009, with final analysis in 2010. There will be one interim efficacy analysis, approximately three years after the start of the trial.

An international Data and Safety Monitoring Board (DSMB) will oversee the trial and conduct at least semi-annual safety reviews.

Multiple Partners, Long-Term Collaboration

Agencies within the Thai and U.S. governments have collaborated for more than a decade in building infrastructure that would support this large-scale efficacy trial. The Technical Subcommittee on AIDS Vaccines, a subcommittee of the Thai National AIDS Commission, and the Ethical Review Board of the Thai Ministry of Public Health (MoPH), approved the trial, along with nine expert panels and Institutional Review Boards in Thailand, the United States and UNAIDS/WHO. Additionally, Thai non-governmental organizations (NGOs) worked with the MoPH on a comprehensive community engagement program.

Trial Update

Screening began on Sept 29, 2003 and the first immunization took place on Oct 20, 2003. As of July 4, 2004 a total of 5,893 volunteers have been screened and 3,435 have been enrolled.

[ALH300]

Encouraging news to say the least! They probably know way more than what they are telling.....

[JamieD]

Walter Reed Medical Centre was conducting HIV Vaccine Trials back a few years ago too. I was enroled when I was 18, but ended up being taken out of the study because I was also bingeing and purging at the time.
Hm. Maybe I wouldn't be infected now if I had completed it. Guess I'll never know.

[Inchlingblue]

This should be completed about now, I wonder when they will publish any results.

Phase III Trial in Thailand

MHRP is in the follow-up stages in Thailand of the world's largest Phase III study of a complex HIV vaccine candidate. The trial enrolled 16,402 study participants at 50 health centers and hospitals in eight districts.

An Independent Data Safety and Monitoring Board met in July 2007 to conduct an interim analysis of the trial in Thailand. The Board recommended that the study continue, because there were no safety concerns with the vaccine. While no firm conclusions can be drawn from this interim analysis for efficacy of the vaccine, predetermined benchmarks for statistical futility were not met. Study officials expect that the trial will continue until the final analysis, which is scheduled for the summer 2009.

LINKS:

http://www.hivresearch.org/global-efforts/thailand.html

http://www.hivresearch.org/vaccine/index.html

[tommy246]

In thailand they have developed an aids vaccine that gives you a third less chance of getting infected thats all i read as it came along the bottom of the screen ,dont know if anyone else has heard about this.

[tendai]

just seen it on CNN. Great news!

[veritas]

Tommy,

Here's somemore info on this wonderful news!:

http://www.pittsburghlive.com/x/pittsburghtrib/news/breaking/s_644726.html

This find could definitely be a breakthrough toward a vaccine that will do more than the 31% that this vaccine protected in the trial. The details will be released in Paris next month.

Even though the vaccine does not work in those already infected, what they learn from this vaccine could move things forward on all fronts.

Never give -up Hope!



v

[veritas]

Here is the vaccine study details:


http://www.hivresearch.org/phase3/factsheet.html

The work goes on!

v

[freewillie99]

WOW

[veritas]

More from the NIH:

http://www3.niaid.nih.gov/news/newsreleases/2009/ThaiVaxStudy.htm

v

[J.R.E.]

Cnn News has been reporting this since 5:45 this morning :

http://www.cnn.com/2009/HEALTH/09/24/hiv.vaccine/index.html


CNN) -- A vaccine to prevent HIV infection has shown modest results for the first time, researchers have found.
Researchers found those who received the vaccine combination were 31 percent less likely to contract HIV.




In what is being called the world's largest HIV vaccine trial ever, researchers found that people who received a series of inoculations of a prime vaccine and booster vaccine were 31 percent less likely to get HIV, compared with those on a placebo.

"Before this study, it was thought vaccine for HIV is not possible," Col. Jerome Kim, who is the HIV vaccines product manager for the U.S. Army, told CNN.

Kim emphasized that the level of efficacy was modest, but given the failures of previous HIV vaccine trials, "yesterday we would have thought an HIV vaccine wasn't possible."

He called the results from the trial an important first step that will help researchers work toward a more effective vaccine.

Researchers have tried to prevent the spread of HIV since they discovered its cause in 1986. Previous vaccine trials failed to prevent infection. And during one trial, the vaccine seemed to boost the chance of being infected, which ended testing early.

The new study was conducted in Thailand, with more than 16,000 people between ages 18 and 30 participating. They were all HIV negative at the beginning of the trial.

Nearly 8,200 received a placebo and a similar number received a combination of six vaccines over six months. All were followed for three years.
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"This shows a statistically significant effect," Kim said.

He cautioned that a lot more research was necessary, because the vaccine did not prevent everyone from being infected.

Fifty-one people in the vaccine group eventually contracted HIV, compared with 74 in the placebo group.

"These results show that development of a safe and effective preventive HIV vaccine is possible," said Col. Nelson Michael, who is director of the U.S. military HIV research program.

The combination of vaccines tested targeted strains circulating in Thailand. It was unclear how the vaccines would work elsewhere, Kim said.

Researchers will announce details of their initial findings in October at the AIDS Vaccine Conference in Paris, France.

The study was funded by the National Institutes of Allergy and Infectious Diseases and the U.S. Army Medical Research and Materiel Command.

According to Kim, the U.S. military was involved in the study because U.S. service members are at risk and "there's a national security threat from HIV."

He said Congress set up a program to protect service members from HIV and the U.S. military has collaborated with health officials and researchers in Thailand for a long time.

The vaccines are manufactured by Global Solutions for Infectious Diseases and Sanofi Pasteur. The Thai Ministry of Health carried out the clinical trial.
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All About HIV and AIDS




Ray

[J.R.E.]

Moderator,

I didn't see Tommy's post in research news.  If you would like to move this post and combine it.


Thanks --Ray

[Ann]

Hi Ray,

I was happy to merge your thread from Living into this thread in Research, as it gave me the opportunity to change the title of the thread without having to edit Tommy's post.

People, PLEASE, when posting new threads here in the Research Forum, give your thread a title that accurately describes what it's about. Use the name of the trial (or study), as I have. This makes it easier for us to keep subjects in one thread, without having three or four threads about the same research news.

Thank you all for your cooperation. And remember, this request is to make it easier for EVERYONE to find the information they're interested in. Cheers.

Ann

ps - I've edited the posting guidelines in our Research Forum's Welcome Thread to include this thread-naming request. 

[Miss Philicia]

Is this the same thing too?

http://forums.poz.com/index.php?topic=13994.0

[Ann]

Is this the same thing too?

http://forums.poz.com/index.php?topic=13994.0

Well spotted, Miss P. I've merged the threads.

Ann
(who tries to keep the place neat and tidy, but it's a never-ending battle)

[bmancanfly]

This is great news for the HIV negative and aweful news for us pozzies.    Once there is a preventative vaccine you can say goodbye to any meaningful energy going into a cure.

[J220]

This find could definitely be a breakthrough toward a vaccine that will do more than the 31% that this vaccine protected in the trial. Even though the vaccine does not work in those already infected, what they learn from this vaccine could move things forward on all fronts.

Never give -up Hope!
v

Absolutely...the importance of this milestone is that it shows that it can be done, and they are on the right track. Hopefully other researchers will hone in on this as well, and work together to develop it further!

[freewillie99]

This is great news for the HIV negative and aweful news for us pozzies.    Once there is a preventative vaccine you can say goodbye to any meaningful energy going into a cure.

I know better than to be overly critical of another's posts lest I incur the WRATH OF ANN, but that post is lame, pessimistic, and simply delusional.  You base your conjecture on what exactly?

[freewillie99]

Interesting comments from GeoVax:

GeoVax lauds Thailand study results

GeoVax Labs Inc. greeted warmly the news on Thursday of the partial success in Thailand of a candidate HIV/AIDS vaccine owned by Sanofi-Aventis and Global Solutions for Infectious Diseases.

GeoVax (OTC BB: GOVX), an Atlanta-based HIV/AIDS vaccine developer, said the Thailand study represents the first HIV/AIDS vaccine trial to show prevention of infection and supports GeoVax’s strategy. The trial included 16,000 volunteers and was supported by multiple agencies including the U.S. Army and the U.S. National Institutes of Health (NIH).

"The partial success of this trial is very important to the GeoVax vaccine, because the vaccine tested in Thailand, like the GeoVax vaccine, was designed to elicit both T cells and antibody," said Dr. Harriet Robinson, GeoVax senior vice president of research and development, in a statement. "The two vaccines that have failed in previous efficacy trials elicited only antibody or only T cells. This was the first efficacy test of a vaccine that elicited both antibody and T cells and is very encouraging for the GeoVax vaccine, because our vaccine generates higher frequencies of T cells and better quality antibody.”

Robinson added that what GeoVax knows about the elicited responses observed in the Thailand study, and the similarities and differences between its vaccine and the Sanofi-Aventis vaccine, the GeoVax vaccine should be poised for a higher level of protective success than the 30 percent success rate in Thailand.

http://atlanta.bizjournals.com/atlanta/stories/2009/09/21/daily72.html

[bmancanfly]

How much money went into curing Polio after Jonas Salk invented the polio vaccine?  I don't want to downplay the importance for everyone else but if you think funds,  and great minds,  will continue to be drawn they way they are now, to a search for a "cure" after an effective preventative vaccine is found, then you are the one who is dillusional.

The posts in this forum are often ridiculously optimistic even when there is little or no reason to be.  Just because I won't drink the kool-aid doesn't mean I'm dillusional.  This is a website for people with HIV.  A preventative vaccine that doen't help the infected is not fabulous news for the infected the same way the polio vaccine was not great news for those already afflicted.

If you don't think that once a preventative vaccine is found that there won't be an enormous shift of money and minds out of the search for a cure, then you're not thinking clearly.

I have many friends who are negative and I want them to stay that way.  So for that reason this is great news for them and humanity.  But selfishly for us on the website - not so much.

[Ann]

I know better than to be overly critical of another's posts lest I incur the WRATH OF ANN, but that post is lame, pessimistic, and simply delusional.  You base your conjecture on what exactly?

Free,

Critisizing someone's post (ideas, opionions) in a respectful manner is one thing - and allowed. However, critisizing the poster personally, as in name-calling or otherwise disrespecting them is what is NOT allowed. I hope you can see the distinction.

I happen to agree that Bman's opinion of this being bad news for us is misguided and overly pessimistic. This advanced is welcome news for everyone, for many reasons.

Bman, you posted while I was writing my own post.

then you are the one who is dillusional.

See, now that is exactly the kind of distinction I'm talking about. Free said your post, in other words, your opinion,  was lame, pessimistic, and simply delusional. He didn't say YOU were. There is a difference. A person can be totally rational, yet hold an opinion or two which seem delusional to others. Get it?

There is every reason for those of us who are already poz to be happy about this news - for ourselves. It's a breakthrough of the type which may lead to a theraputic vaccine for US. In no way does it make me think they'll stop looking for a cure or better treatments just because of this development. Quite the contrary, many scientists are somewhat competitive and this may light the fire under a few labcoat covered butts.

Ann
(who doesn't have a wrathful bone in her body)

[freewillie99]

Thanks, Khan, er, I mean Ann.  Glad I escaped your wrath.

[sensual1973]

yes a preventive vaccine is not good news for us already infected,it will only make us completely forgotten in no time.and the only thing we would see from pharma companies is new HAART with vanilla,chocolate,or strawberry flavors !

[MYSTERY]

This is great news for the HIV negative and aweful news for us pozzies.    Once there is a preventative vaccine you can say goodbye to any meaningful energy going into a cure.

I don't think most of us are going to see a cure in our lifetime anyways. If you think about it, if they got a preventative vaccine death would become a natural cure to HIV once the infected people naturally died off, and then people would be vaccinated against HIV and would not catch it. That would be a cure for this epidemic. Sad, but death kinda has a natural way of curing things.

[georgep77]

yes a preventive vaccine is not good news for us already infected,it will only make us completely forgotten in no time.and the only thing we would see from pharma companies is new HAART with vanilla,chocolate,or strawberry flavors !

I would love HAART with mango flavor !   
                                       

[freewillie99]

I don't think most of us are going to see a cure in our lifetime anyways.

Wow, the pessimism here is deafening.  Please explain and elaborate a bit on this point.  If it's solely based upon how you "feel", it's nothing more than an unsupported assertion.  My optimism is based on the ever increasing rate of technology and advances in areas not even in existence 10 years ago (plotting the genome, gene manipulation, gene silencing, medications with little to no side effects, identification of the reservoirs where HIV hides and advances towards eradication of these, etc).

The so-called German Patient was cured.  So in essence we've already seen a cure in our lifetime.  It's called proof of principle.  Whether technology will enable researchers to duplicate what was done there in a less invasive and dangerous way isn't known yet.  However, given the rate of discovery and new technology, I know I'm not betting against it.  

[tommy246]

yes a preventive vaccine is not good news for us already infected,it will only make us completely forgotten in no time.and the only thing we would see from pharma companies is new HAART with vanilla,chocolate,or strawberry flavors !

You are wrong any vacine to stop people getting infected would mean they are on the right track and will lead to other breakthroughs .

[sensual1973]

how did they know that those 31% were immune to hiv ? , did they deliberately tried to infect them and failed ?!!
 

[veritas]

Let me give you my take as to why this vaccine advance is not only great news for  the HIV-, but also for the HIV+.

For a vaccine to be viable (ie: accepted by the FDA) , the vaccine needs to be at least 70-80% effective against the pathogen. While the Geovax vaccine came in at 31%, a preventative vaccine will have to be a lot more potent. 31% is something that has  never been done, but there are still many questions unanswered. They need something else to stimullate a strong enough immune response.
What are the options:
1. Increase the dosage?
2. Are the antibodies being made strong enough to do the job for everyone?
3. Are there any consequences to the above?
4. Could they add more potent neutralizing antibodies ?
5. How many of the trial participants adhered to the safe sex talk given to them after vaccination?
6. Will the percentages go up or down over a longer period of time?
7. Could something be added to the vaccine to stimulate B-cells' production of the "right" kind of antibody that will not only prevent infection, but also control it? (a two-for one)? ......
Think of somemore what-ifs.

Still a lot of work to be done and more breakthroughs to be found. For those that think science will stand still after  a preventative is found ( if a preventative is found first) think of this: There are more than 30 million people infected with this virus world wide. The strain on healthcare systems around the world is immense just to control the virus itself let alone the AEs and OIs. This is unsustainable. Besides, a patient population of 30 million is a huge insentive enough for the  work to go on.
The work will  continue on all fronts !!!!!!

v

[NYCguy]

just a few musings and riffs on the subject at hand...

I have to admit that, although I am totally gun-ho about vaccine development and watch the studies closely, part of me would really like to see a successful cure or therapeutic vaccine BEFORE the eventual truly successful preventative comes out.  I know it's paranoid..but I can't help but agreeing somewhat that there is some truth to the idea that funding and interest will gradually shift away from treatment, once a successful vaccine is in place.  That said - one of the reasons I am still so pro-vaccine research is that because of the way HIV works on the immune system, any truly effective preventative is more than likely to work therapeutically as well, perhaps with a few tweaks, which does help me sleep at night (fortunately I'm not on Sustiva, so I don't have giant, flying vaccine needles attacking me in the middle of the night).

One little correction - veritas, the Thai vaccine is not Geovax.  Geovax simply commented and 'congratulated' the Thai results, as a way of pointing out that THEIR vaccine is similar but better.  I'm sure it was completely altruistic, especially since their stock volume went from an average of 400K to 8M and jumped by 50% after the comments.

Ok and am I missing something, but out of 16,000 (!!) people 51 vs 74 went poz?  Is this really statistically significant?  Please tell me I am...

[Miss Philicia]

Ok and am I missing something, but out of 16,000 (!!) people 51 vs 74 went poz?  Is this really statistically significant?  Please tell me I am...

Hope nobody here accuses me as being a "downer" because that is not my intention in posting this.  I just read it earlier today and it relates to this question.  Feel free to object.

source

While the media loves a big story, these results were underwhelming. Although they were "statistically significant," it is way too early to declare success. A simple look at the numbers is more sobering: after vaccinating 16,000 people, there were 23 fewer new infections in patients receiving the vaccine (51 cases versus 74 cases). If one additional patient who received the vaccine became infected (52 instead of 51) the results would no longer be "statistically significant."

A misunderstanding of statistics and study design often leads to premature optimism as well as fear, when new studies come out. Today we learned that a combining multiple injections of two vaccines that proved unsuccessful in the past may reduce the chance of new infections. I remain hopeful but VERY skeptical, given the modest differences and lack of biological evidence (there was no difference in viral loads between vaccinated and non-vaccinated patients who acquired HIV). While I am encouraged by the efforts and work being done to develop a vaccine, we have yet to find a silver bullet.

[Inchlingblue]

Ok and am I missing something, but out of 16,000 (!!) people 51 vs 74 went poz?  Is this really statistically significant?  Please tell me I am...

Results: New infections occurred in 51 of the 8,197 given vaccine and in 74 of the 8,198 who received dummy shots. That worked out to a 31 percent lower risk of infection for the vaccine group.

I'm  not a statistician but I thought the same thing: how can this be "statistically significant"? (Thanks, Miss P for the article with the 4-1-1 on the math). I'm just wondering if they were very careful to control for high-risk groups (MSM, sex workers, injection drug users) to be evenly distributed between the two groups, otherwise you've got some skewed results.

I read two contradictory descriptions of those who participated in the trial:

One article (pittsburghlive.com) said: The study tested the combo in HIV-negative Thai men and women ages 18 to 30 at average risk of becoming infected.

But another article (reuters.com) said: The trial was organized by the Thai government and military, who recruited 16,000 ordinary people considered at "community risk" of getting HIV. "What we mean by community risk is that we would include everyone in the community," Kim said. That includes a few commercial sex workers, men who have sex with men and perhaps injecting drug users -- all of whom would be considered at high risk of HIV. But many ordinary people at no extra risk also took part.

The way I see it the only way the results can be valid is if the higher risk individuals were evenly distributed between the two groups.

Who knows, in a few weeks' time we may be seeing another article saying "Woops! Maybe this vaccine didn't work after all" since one group had too many drug addicted gay whores!

[SASA39]

Yes , this is a first truly reliable great news in a past few years .
But it raises a dozen of questions :

1.The vaccine is only 30 % effective , and with a HIV strain present in Thailand.
What kind of virus part make it ineffective on the other 70 % , and what would be if that kind of vaccine  is implemented on HIV strains in other parts of the world - Africa and Europe ?

( For the vaccine to be effective a minimum percentage is 98-99 , and it could be achieved if scientist could find a part of virus that is unchangeable and vulnerable and make a vaccine as aresult of those two facts.)

2.The vaccine is preventive type not a therapeutic one.Also a latest report from pharma companies stated that they put a little effort to find a new drugs with less side-effects.
Is that mean that all of us are going to be " left with the flood" ?

3. Is there a way to convert that kind of vaccine into therapeutic one ?
Is there is a possibility for all 7,000 , and more of us in POZ .com  to make any kind of petition to a certain U.S army.Drug company ?

And I must admit that I feel sorry for those poor people who has volunteered to be infected with HIV even with a government guaranties for their HAART treatman.

Al

[Inchlingblue]

And I must admit that I feel sorry for those poor people who has volunteered to be infected with HIV even with a government guaranties for their HAART treatman.

No one volunteered to be infected with HIV. Both groups were given counseling and plenty of condoms and were told to play it safe etc. When you've got 16,000 people there are those who will still slip up and fall off the wagon.

The vaccine, if it is proven to be effective, does appear to work against the main strain found in the US & Europe, which is clade B. That's no consolation to those in Africa and other poor areas but just saying, it's not just the strain found in Thailand.

[Puckslinger]

Hiya Gang,

I just saw this in the news. I am wondering what people think about it.


http://www.webmd.com/hiv-aids/news/20090924/aids-vaccine-success-modest

AIDS Vaccine Success Is 'Modest'

First-Ever Protective Effect Is Small but Suggests HIV Vaccine Is Possible

 By Daniel J. DeNoon
WebMD Health News

Reviewed by Louise Chang, MD

Sept. 24, 2009 - "Modest" success in an HIV vaccine trial shows for the first time that vaccination can protect people against infection with the AIDS virus.

It's a small but significant step forward. Few, if any, think this vaccine is effective enough to deploy in the worldwide fight against AIDS. But many experts say it offers badly needed hope to an effort marked by many expensive failures.

"While these results are encouraging, we recognize that further study is required to build upon these findings," Col. Nelson Michael, director of the U.S. Military HIV Research Program, says in a news release.

The trial was a collaboration between the U.S. Army, Thailand, the U.S. National Institute of Allergy and Infectious Diseases, Sanofi Pasteur, and Global Solutions for Infectious Diseases. It tested Sanofi's ALVAC vaccine boosted with a dose of GSID's AIDSVAX.

Conducted in Thailand, it began in 2003 and enrolled 16,402 adult, HIV-negative men and women. Half got the two-part vaccine, and half got inactive placebo shots.

Over the course of the study, 74 placebo recipients and 51 vaccine recipients became infected with HIV. The difference isn't large, but it translates into 31% vaccine effectiveness. That is, it lowered the risk of getting HIV by 31%.

That's "an important step forward in HIV vaccine research," NIAID director and long-time AIDS researcher Anthony Fauci, MD, says in a news release. "Certainly this is an encouraging advance."

Even so, the study results are puzzling. It was expected that vaccine recipients who became infected would at least have some protection against the virus. But the study found no evidence of such protection. HIV levels were just as high in vaccine recipients who became infected as in placebo recipients who contracted the virus.

Perhaps more importantly, the study fell far short of its goal of reducing the risk of HIV infection by 50%.

The study was controversial from the outset. It's the largest HIV vaccine trial yet conducted, and some AIDS activists called the study a waste of precious resources.

AIDSVAX, the first HIV vaccine ever to be tested, had already failed to prevent HIV in a number of trials. ALVAC, a live canarypox virus carrying HIV genes, did not appear to stimulate strong immune responses in healthy people. And similar combination vaccine strategies showed little evidence of eliciting strong immune responses.

Moreover, a similar study of the ALVAC and AIDSVAX vaccines had been canceled in the U.S. And critics said the study design would make it hard to tell which part of the vaccine regimen was or was not effective.

Now that the study is completed, researchers will go over the data with a fine-tooth comb. They'll try to figure out what worked and build on that success.

"Knowledge gained through this study will be used to accelerate future study design and testing as researchers continue the search for a safe, globally effective HIV vaccine," Col. Jerome Kim, HIV vaccines product manager for the U.S. Army, says in a news release

[SASA39]

Yeah , I was wrong about that fact.

[veritas]

NYCguy,

Thanks for the correction to my post. You are correct it is not Geovax ---- my error for not having my brain and typing skills in cync. (lol).

Miss Philicia,

I think we are all in agreement that this particular vaccine is not the silver bullet. The statistics are only good for the time alottted (a point in time). Next week two or more people from the vaccinated group could become infected and the stats change. However, for this study design and time those were the statistics and thats the first time that type of result was found with HIV. There's a long way to go. Let's wait to see the data review, hopfully completed by the Paris conference.

Inch,

I hope we don't get that "WHOOPS" also but it is a possibility. Usually when atrial like this is set-up it is blinded so no-one knows who is getting the vaccine and who is getting the placebo. It should all be by chance so the statistics should be valid ( again data review needs to be done). I hope they didn't cheat!

SASA,

I don't believe a vaccine has to be 98 or 99% to be approved or effective. Take the Guardicil vaccine --that is only 93% in women and their about to approve it for men:

http://news.yahoo.com/s/hsn/20090909/hl_hsn/fdapanelweighsapprovinghpvvaccineformales

A 70 or 80% effective vaccine for HIV would put a dent in the epidemic.

They have found non-mutatable parts of the virus --- the trick is to mount a strong enough immune response and get to the latent cells for a cure or get to all freeflowing virus by some type of adaptive immunity so our immune systems can at least control the freeflowing virus -- work on the aforementioned is being done.
I thought the news was  a step in the right direction.

Let's wait to see what happens in Paris next month!

v

[J220]

Who knows, in a few weeks' time we may be seeing another article saying "Woops! Maybe this vaccine didn't work after all"...

Actually I was thinking this over, and frankly I would not be surprised this could turn out to be the case. I mean, if in fact the vaccine did prevent some infections, then yes, it is a great step forward. But...

There was only a difference of 23 non-infections in the vaccinated group, compared to the placebo. And this is out of 8197, so this is mighty small....how do the researchers really know that the lower number in the vaccinated group was really the result of the vaccine? Especially when they saw no therapeutic benefit whatsoever in the vaccinated arm among those that did get infected?? Hmmm.

As far as I'm concerned this small difference could have been anything, and we cannot rule out it was the result of pure chance in the vaccinated group, perhaps different behaviour, maybe even a difference in the pre-trial counseling that was provided to the two different arms, who knows?

Hope I'm wrong, obviously, but I will revise my earlier optimism and reserve it for a little further down the line until they can analyze this data more rigorously.

[Inchlingblue]

Inch,

I hope we don't get that "WHOOPS" also but it is a possibility. Usually when atrial like this is set-up it is blinded so no-one knows who is getting the vaccine and who is getting the placebo. It should all be by chance so the statistics should be valid ( again data review needs to be done). I hope they didn't cheat!
 

I don't think they cheated I'm just saying that with some high risk groups, for example MSM there are men on the DL who don't admit to having sex with other men, or people who are sex workers or IV drug users who also don't admit to it. If individuals from the high risk groups were not evenly distributed between the two arms (without the researchers even realizing it) then the results would be skewed one way or the other.

Bottom line is they will be looking at this data with a fine tooth comb, I think it's too soon to really know what the numbers mean.

Actually I was thinking this over, and frankly I would not be surprised this could turn out to be the case. I mean, if in fact the vaccine did prevent some infections, then yes, it is a great step forward. But...

There was only a difference of 23 non-infections in the vaccinated group, compared to the placebo. And this is out of 8197, so this is mighty small....how do the researchers really know that the lower number in the vaccinated group was really the result of the vaccine? Especially when they saw no therapeutic benefit whatsoever in the vaccinated arm among those that did get infected?? Hmmm.

You're right, these results are a hair's breadth from not being "statistically significant." All of these studies rely on statistics and the fact that 51 people in the arm that received the vaccine got infected made these results "statistically significant." As the article that Miss P cited said, if just one more person had been infected to make it a total of 52, then the results would not have been considered statistically significant. So this is pretty darn close.

I think the excitement comes from the fact that these results are so much better than any previous attempt with an HIV vaccine so some researchers and people who follow this were expecting much worse numbers and the results ended up surprising everyone.

[elf]

I guess cocktail vaccine is needed (with 4 or more different vaccines combined) which is similar to HAART...
All monovaccines were ineffective, so the key is to use more antiHIV vaccines together...

[loop78]

Regarding the statistical significance of the trial results (source:aidsmap)

In the event, the prime-boost combination of ALVAC(R) HIV and AIDSVAX(R) B/E lowered the rate of HIV infection by 31.2% compared with placebo. This reduction was statistically significant, meaning that the possibility that the possibility of the result being due to chance is very low, but the confidence intervals for the estimate in the reduction in risk were wide (p=0.039, 95% confidence interval 1.1% - 51.1%).

So while it's true that the results are technically "statistically significant", I think they warrant further study. Especially, taking into account there was no reduction in the mean viral load between those who received the vaccine and still were infected and the infected ones who got the placebo. IMHO, assuming the vaccine really worked, this could mean either that this vaccine approach only works as preventive one (and once the single virus that is supposed to originate most transmissions manages to break the defenses elicited by the vaccine, it has no effect), either there is something more we do not still comprehend about the way the immune defense works with hiv. To sum up: what I said before about studying this further :-)

Anyway, even if this approach leads to a preventive only vaccine, I believe it's also good news to us. Not only because any scientific advance in the field may contribute to an eventual, functional or otherwise, cure, but also because a truly preventive vaccine would do lots about reducing stigma and poz-fear, and that nowadays is a great part of the burden hiv imposes to us.

[SASA39]

But one thing still puzzles me :
If volunteers were divided into two groups - one with placebo and one with vaccine , and it had been told them to practice safe sex , then how after a few years researches knew if they had practiced safe sex , sex at all , or they were sex workers who practiced unsafe sex frequently every day ?
Who monitored them , because at the questioning they could tell anything they wanted to ?

And for veritas : with this kind of tramsmission  , my opinion is that effectiveness of the vaccine should be more than 95 % , because that will be the way to stop spreading.
Al

[veritas]

SASA,

I agree with you, I do hope they come up with a vaccine that is 95,98 or 99% effective. However, my post meant to show that the FDA would welcome a vaccine that rendered protection to 80% of the population and such a vaccine would put a dent in the epidemic.

I don't think that anyone following my posts can put me in the category of pessimists. I'm following research and development because I believe research is on the cusp of a major breakthrough. Let me reiterate, my interest in anti-ps is based on the fact that flipped PS is a non-mutatable part of both the virus and infected cells. If they find a way to deliver a potent enough immune response to that target then we have the potential for both a cure and a vaccine. Millions of dollars and hundreds of researchers are involved in developing anti-ps research since it is a common target for many viruses, bacterior and cancer. The "holy Grail" if found. So believe me when I say "we're on the same page."

Also, let me say, if someone finds another pathway to a cure , I'll hail that also. The work is progressing on many fronts, the race goes on and it's happening!


v

[megasept]

just seen it on CNN. Great news!

Everyone: If people are told they are getting this anti-HIV vaccine won't they think they are protected and engage in riskier sexual activities than before? Reminds me of circumcision campaigns (to combat HIV and other STDs) in S. Africa (among other areas of the world). Do you think those guys use a rubber after being told they have participated in an HIV reduction/prevention measure? Doubt it.

Medically this vaccine news is exciting (if it eventually leads to a 99%+ successful vaccine). Socially, it's a dud.

-megasept

[J220]

Everyone: If people are told they are getting this anti-HIV vaccine won't they think they are protected and engage in riskier sexual activities than before?

Perhaps to a degree, but remember, the volunteers were simply told they were receiving either the placebo or the vaccine, but not which one. So they did not know for sure they got the vaccine, and furthermore, if the vaccine was going to work. But I can see how someone would think that there is a 50% chance they received the vaccine...and another chance the vaccine woud work, and have this influence their behaviour. In fact this was on NPR yesterday and they had an excellent disussion about the complex ethics of vaccine trials.

[David Evans]

In terms of vaccine and other prevention measure development, most of the clinical trials networks have thus far done an excellent job of ensuring that the overall risk-taking has actually gone down in stuides- and not up. This has been achieved through extensive counseling and education, provision of condoms, etc. The CDC and other stakeholders have taken an extremely responsible position on this issue as the way they are talking about things like PrEP. They say that no matter how successful a new prevention tool might be, it must be used in combination with all other proven prevention methods - that what we're shooting for is a prevention package.

Granted, this won't ensure that additional risk never happens if someone perceives themselves to be protected by whatever becomes available (PrEP, microbicide, vaccine), but the CDC does plan to issue strong recommendations about proper prevention counseling to be conducted along with prescriptions for anything that ultimately proves effective.

In terms of hopes or skepticism about these results, it seems that here are valid reasons for both. The traditional press usually glosses over complexity and this is a perfect example where the results are not at all straightforward. The complete data have not been provided thus far, so it's very difficult to determine how compelling these results are going to be. It seems there is at least a possibility to learn more about the mechanics of protection from infection, and then use those learnings toward more promising vaccine approaches. That would be great.

I also want to reassure you that groups like Project Inform, ATAC and others are doing everything we can to make sure that the search for a cure for people who are already positive doesn't fall off of the agenda. Before he died, the activist Martin Delaney was successful at getting the NIH to coordinate and devote additional resources to this end. There's still a LOT we still need to learn on a basic science level about the immune system and viral reservoirs, but progress is being made. I hope people don't give up all hope.

David

[veritas]

David,

Bravo !!!  A good even-keeled response to a story that certainly can  be sensationalised by the main stream media with the main point being drowned in the hype.

What stood out for me was Fauci's comments:

"These new findings represent an important step forward in HIV vaccine research,” says Anthony S. Fauci, M.D., director of the National Institute of Allergy and Infectious Diseases (NIAID), part of the NIH, which provided major funding and other support for the study. “For the first time, an investigational HIV vaccine has demonstrated some ability to prevent HIV infection among vaccinated individuals. Additional research is needed to better understand how this vaccine regimen reduced the risk of HIV infection, but certainly this is an encouraging advance for the HIV vaccine field"

Martin Delaney must be smiling !!


v

[Ann]

what we're shooting for is a prevention package.

"Prevention package. I like that.

Ann

[Ann]

I also want to reassure you that groups like Project Inform, ATAC and others are doing everything we can to make sure that the search for a cure for people who are already positive doesn't fall off of the agenda.

I wanted to repeat what David said above because it's relevant to some of the Research forum regulars. Those of you who are adamant that the search for a cure - or even better treatments - will cease with the development of a vaccine might want to think about joining one of the advocacy groups. Sitting at home, wringing your hands and bemoaning the fate of us pozzies should a vaccine be found will achieve absolutely nothing. Getting involved in an advocacy group will  achieve something and we have plenty of examples in the history of hiv/aids to show just how true this is.

Don't just sit there, DO something! We need a new generation of activists. And we need them NOW.

Ann

[freewillie99]

"Prevention package. I like that.

Ann

Heh...which is it, Ann?  Do good things come in big or small packages?

[Ann]

Heh...which is it, Ann?  Do good things come in big or small packages?

Big, of course!

[bmancanfly]

There is a very strong bias in this forum toward overly hyping ever scientific advance, no matter how small or inconsequential.  Any time someone dares to not go along with the Polyanna happy talk their posts are attacked as "lame, dellusional, pessimmistic" or something simliar.  

It's almost like the regulars here don't want to hear anything other than "the end of HIV is right around the corner".  I think it's dissingenuous to suggest that it is and to keep presenting every medical/scientific advance as if we were right on the brink of a cure (functional or otherwise) is misrepresentation at the very least.  

We are a long way from the end.  And that's not pessimism, that's reality.  By any objective measure, that's reality.

I don't want to downplay the many advances that have taken place lately, because they are important, but the reality remains the same.

To clarify my earlier comments;  If we were to chart the money spent for an HIV cure and the search for new drugs on a graph, the highwater mark on that chart will be the year they discover an HIV preventative vaccine.  I don't see how you can argue that funding will remain constant, or increase,  once the threat of new infections has been eliminated or drastically reduced.  Now you can certainly debate how quickly the decline will occur, either rapidly or gradually over time,  but to argue that it won't decline at all.  Really?

HIV receives a disproportionate amount of funding in relationship to other diseases, based on the number of people afflicted,  and I , selfishly think that that is a great thing.  The rationalization for doing so is that without the additional efforts, HIV (since it's contagious) could mushroom into a  much bigger problem than it already is now.  But once a preventative vaccine is found, how do you justify the additional funding?  There are already other disease constituancies that are jealous of the disproportionate amount of money spent on HIV - not to mention the political enemies who always oppose HIV funding.  Plus, do you really think that corp. CEO's are going to invest tens or hundreds of millions of dollars to develope new treatments once the spigot of new customers ($$$$$) has been turned off?  And again, I'm NOT saying ALL reasearch funding, but the decline in funding will begin.

I hope this whole debate becomes irrelavent when/if the vaccine that actually works to prevent, also works therapeutically.

But  I still don't think expressing concerns about a solely preventative vaccine are totally misplaced.

As for Ann's comments about advocacy work, I wholeheartedly agree.  I have done more than my fair share over the years, even before I was infected.  I encourage those younger and healthier than I to follow suit.

[newt]

I encourage people to read Michael Palm's excellent summary of this announcement on the Treatment Action Group Basic Science blog:

http://www.treatmentactiongroup.org/basicsciblog.aspx?id=3356&blogid=88

The article has web links including to an MP3 recording of a key conference call about the results.

Michael Palm reports that the likely effectiveness of the vaccine was somewhere in the range of 1.1% to 52.1%*, a wild variation -- especially considering a difference against the placebo of less than 1% would be is regarded as no difference at all.

So, did it work, or didn't it? hmmm



* 74 out of 8,198 volunteers who received placebo immunizations became infected with HIV compared to 51 out of 8,197 volunteers who received a combination of two vaccines, ALVAC vCP1521 and AIDSVAX B/E. Efficacy calculated at 31%, 95% confidence interval: 1.1%-52,1%, p value: 0.039.  7 volunteers were excluded from the efficacy analyses after it was found that they were HIV+ at the time of receiving their first vaccination.

[veritas]

bman,

I am going to answer your post, not to disparage your opinions but to clarify some facts that I believe were inaccurately assumed.

1. If you read what most posters actually say in this forum, I have never read where anyone claimed that a cure was around the corner as much as we all hope there will be. I do see a lot of optimism concerning up and coming therapies that are new and have the potential to be a breakthrough. I have not read any timelines given for a cure, only that there is a lot of potential and "thats a good thing".

2. No facts to my knowledge have been mis-represented ( please point out if I am wrong) they have just been stated with the hope of further development in a positive way. They have their opinions also and as an opinion  ( right ,wrong or indifferent) they can state them as long as it's based on some type of relevant research. If someone wants to refute a certain opinion, without a personal attack and can back it up with further research that's OK.

3. Although the general feeling in the research community is that a cure or a vaccine is a long way off, there is always the possibility that by doing all this research a breakthrough could occur even by accident
and all those predictions go out the window (read about penicillan).

4. I would also like to know the source of your information concerning funding. There are over 33 million people afflicted with HIV/aids worldwide and although it's considered a "manageable dis=ease" in western countries, that is not the case in most of the world (look at Africa). The funding for HIV is not in the top ten. It seems that way because HIV is a good story an d constantly in the news. My resource for the aforementioned statement is from the NIH:

http://report.nih.gov/rcdc/categories/Default.aspx

If you have information to the contrary, I would be happy to discuss/ review it with you if the source is reputable and fact based.

5. As far as research being drastically reduced after a preventative vaccine is found (although this statement will be a hypothetical since a preventative vaccine has not been found yet) I believe that researchers can use HIV as a model to further study the workings of the immune system and other diseases.

We are certainly not in agreement with our visions as to how research is proceding , but I have given you my rebuttal and if you wish to discuss further please reply.

Deep down I think we are all hoping for the same result.. History has been less than kind to those of us suffering from this disease ( the  advances not withstanding). Lets all work toward the goal of not having history repeat itself.

I hope you take my post in the positive way I meant it to be.


v











 

[veritas]

newt,

I read your link provided. We are certainly in agreement that the data most be further analyzed. However, even if Michael Palm's statistics are  proven to be true in the lower range, I know you've got the savvy to understand " A journey of a thousand miles starts with one small step".

Did it work ?

v ( who is hopeful because difficult times lead to better days)

[freewillie99]

There is a very strong bias in this forum toward overly hyping ever scientific advance, no matter how small or inconsequential.  Any time someone dares to not go along with the Polyanna happy talk their posts are attacked as "lame, dellusional, pessimmistic" or something simliar.  

bmancanfly,

Since you attempted to quote me (albeit with horrendous spelling - is english your first language?) I'll make a couple of comments to your incredibly lame post.  You make, as always, many unfounded and unsupported assertions.  When called on it you cry like a little girl.  Boo freakin hoo.  Your conspiracy theory gobblygook is especially annoying. 

Please provide links to support your claims of Pollyannas crowing about a cure being "right around the corner".  Of course you can't, because no one has. 

This is the Research forum, not the Debby Downer forum.  No one wants to hear your unsupported ideas.

[Ann]

Since you attempted to quote me (albeit with horrendous spelling - is english your first language?) I'll make a couple of comments to your incredibly lame post.  You make, as always, many unfounded and unsupported assertions. When called on it you cry like a little girl.  Boo freakin hoo.  Your conspiracy theory gobblygook is especially annoying. 

Please provide links to support your claims of Pollyannas crowing about a cure being "right around the corner".  Of course you can't, because no one has. 

This is the Research forum, not the Debby Downer forum.  No one wants to hear your unsupported ideas.

Free,

Did you read a word I wrote above about personal attacks?  Keep it up and you'll be given a time out.

This is the Research forum, not the Playground forum. If you cannot put your disagreements across in a civil, adult manner, keep them to yourself.

Please consider yourself warned.

Ann

[freewillie99]

This is the Research forum, not the Playground forum.

Good line.  Yes, Ann.  I did read what you wrote.  I'll monitor my behavior.

[veritas]

The NYT blasts the Thai aids vaccine results but gives a vivid description as to why a vaccine is necessary--- not a pretty picture:

http://www.nytimes.com/2009/09/27/weekinreview/27mcneil.html?_r=2&scp=2&sq=&st=nyt

A cure must be found !!!

v

[freewillie99]

The NYT blasts the Thai aids vaccine results but gives a vivid description as to why a vaccine is necessary--- not a pretty picture:

v,

That editorial is scathing.  Can't really find much fault with it though.

Polly

[bmancanfly]

Sounds like I hit a nerve.

I stand by my comments as they are correct.  Sometimes the truth is unpleasant.


P.S. Veritas I disagree with your post, but appreciate your civil reply.  Peace

[freewillie99]

Sounds like I hit a nerve.

I stand by my comments as they are correct.  Sometimes the truth is unpleasant.

Heh...thanks for the hearty laugh.  Pessimistic blowhards, naysayers, and purveyors of "not invented here" are a dime a dozen.

[georgep77]

I stand by my comments as they are correct.  Sometimes the truth is unpleasant.

you love yourself, dont u !!!!   

[Ann]

Sounds like I hit a nerve.

I stand by my comments as they are correct.  Sometimes the truth is unpleasant.


P.S. Veritas I disagree with your post, but appreciate your civil reply.  Peace

Heh...thanks for the hearty laugh.  Pessimistic blowhards, naysayers, and purveyors of "not invented here" are a dime a dozen.

bman, free,

The back-and-forth sniping between the two of you is getting tedious. It stops here and it stops NOW. If you cannot add to the discussion about this vaccine without the sarcastic comments, then DO NOT POST.

you love yourself, dont u !!!!   

George - this applies to you, too. Enough already!

It also applies to anyone else who might want to join in. DON'T.

The next person who posts any sort of personal attack or further comments on this Polyanna/Pessimist debate in this thread is getting a time out.

If you guys want to debate the Polyanna/Pessimist issue, start a thread for it. I'm tired of threads that are supposed to inform people about research news getting turned into slanging matches.

IT STOPS HERE.  Got it?

Ann

[NYCguy]

Hmmm, well.. i was going to say that topics with titles like "Could this be the Holy Grail" I do find a bit tedious, but that it's really just a few people and in general these forums are fairly sane and very informative... But let's just pretend I didn't say that. 

What I REALLY want to say is that the NYT editorial is, as Free said, quite scathing but I have to agree - I can't really find anything wrong with it.  I keep turning it over and over in my head and true, I'm not a statistician, but I just can't help but feel that this really isn't statistically significant.  I mean how can it be with such an extremely small percentage of such a large group?  There are so many factors that could have contributed to the small difference, especially considering that no protection was found from the vaccine. 

I know that a lot can be learned from what doesn't work, and I hope that it is.  But it seems for now that a new direction in vaccine development has not been proven.  As a small aside, I would add that I was a volunteer in the notorious Vaxgen trial in the 90s.  We really didn't have any way of knowing if we had taken placebo or vaccine (I ended up having vaccine) and they did give counseling, but it's true that there is a psychological component to this where you can't help but think you MIGHT be protected.  After the trial ended (and I read about it failing in the NYT BEFORE the trial center informed me - not the way to make your volunteers happy, by the way) I then found out, again not a peep from the New York Blood Center, that there was a theoretical possibility that the vaccine could make you more susceptible.  The whole thing was quite a debacle and I was really freaked.  I guess all this to say that I truly appreciate the sacrifice that vaccine volunteers make and that they deserve to be treated with dignity and with only the best that science can provide, be they in Thailand, Africa, Canada or the good 'ole USA.

I guess this was a bit of a meander...thanks for listening

[megasept]

I don't think they cheated I'm just saying that with some high risk groups, for example MSM there are men on the DL who don't admit to having sex with other men, or people who are sex workers or IV drug users who also don't admit to it. If individuals from the high risk groups were not evenly distributed between the two arms (without the researchers even realizing it) then the results would be skewed one way or the other.

Bottom line is they will be looking at this data with a fine tooth comb, I think it's too soon to really know what the numbers mean.

You're right, these results are a hair's breadth from not being "statistically significant."

This discussion is good, and obviously we all could use some more education in statistical analysis (I have no education in this). Some of the tension here between those who are pessimistic and optimistic may lie as much in the fact that we've never been taught this stuff, as our "nature". Ann's warning is duly noted.

I have never understood statistical "error level". "Significance?" Anyone? It certainly matter if the "two arms" of the study were not equivalent. And that does happen.

Yes, sex workers, or MSM might be a higher risk group than say, older females. But saying that doesn't mean higher risk people need to be excluded from data collection. In fact, it might be very helpful to identify and recruit them. Virgins and monogamous folks wouldn't be the best source for studies on STD transmission, Studies of HIV- prostitutes---their customers are the danger---have been helpful in proving effectiveness of rubbers, for intercourse.

I suppose the bigger the sample and control for location (city vs. rural), age, wealth, educational level, occupation, types of drug use, single or married, gay or ?, gender, access to healthcare, would be example of factors that would be imputed. Few studies try to find subjects who are all equivalent (some twin studies excluded). Identifying relevant differences and then comparing the data this way or that (controlling for one or another aspect) is part of the analysis.

In a dumb sense huge samples are more meaningful than tiny samples. But it is much more complicated than that.

One way to make more of a study is for other researchers to analyze the same data (often just a piece of it). Often the conclusions are somewhat different than the first time around. This is pretty common. It is common to try "replication" of results in hard science, but also common to see the process happen in softer science I just described, if only because it's a whole lot cheaper to look at someone's else's data than design a study and collect your own.

SF State Univ. did a good long term study of gay men who were LTPoz, mostly drug-users, all of whom had unprotected intercourse, and their long-term health. The high risks these men took over many years of study was what made the data meaningful. Ethics dictate study design not encourage participants do themselves harm, but I think my point can be understood. Tuskegee (exposure) can be thanked for progress in ethical study design.

Study participants lie for many reasons, including access to the benefits of trial participation. I was just in a drug trial where I was told what results I needed to report daily to gain access into the longer study and use of a placebo or real med, followed by the real med. That's not honest. I didn't mind the info; I wanted the drug in the study. Incentive to lie!

Good studies build incentives for truthful disclosure and desired behaviors (Drug tests are an example of a useful disincentive). Scientific studies that require NO self reporting of anything are ideal. Sometimes the subjects are ALL dead, and their medical records are combed thru for data.

Knowing males from Town A died on the average 1.5 years before males from Town B might point to the steel furnace in Town A, or maybe it was milk consumption that made the difference. Everyone takes credit when unemployment or crime drops, but points somewhere else when folks lose their jobs or break-ins rise. Cause is hard to pinpoint.

Many studies are poorly designed. Some are tainted based on who is paying the bill. I am not saying either element applies in this vaccine trial.

It helps all of us to learn a little about these processes. I would like to read a good introductory book on the subject of statistical studies, if someone could suggest a title. Many of you have carefully laid out the positive aspects of this vaccine study (Thanks!) , and no doubt you are right this is a step forward. Maybe for those of us with HIV as well.

  -megasept

[lusopt]

I feel glad that a vaccine is being achieved for HIV- people, but shouldnt it be more important to discover better treatments or even a cure for this.

Sadly its obvious (at least for me) that we all are going to be forgotten, they are just going to wait for us to die, it kinda depresses me when i read the success of this vaccine, the more success they have, more doomed we are. Why spending rivers of money on researches for a small percentage of people living with HIV, if they know that the disease ends with them.

Is it only me, who sees things this way?

[Assurbanipal]

It helps all of us to learn a little about these processes. I would like to read a good introductory book on the subject of statistical studies, if someone could suggest a title. Many of you have carefully laid out the positive aspects of this vaccine study (Thanks!) , and no doubt you are right this is a step forward. Maybe for those of us with HIV as well.

  -megasept

Wikipedia is like nectar to the math geek honeybee so you can assume what is up there has been heavily patrolled and policed.  http://en.wikipedia.org/wiki/Statistical_hypothesis_testing
But it is not always written for ease 
Here's a link to another article that may be helpful. http://www.ericdigests.org/1995-1/testing.htm

But basically the problem here is that they used a 19 times out of 20 test to decide whether their results hald water and were awfully close to the edge on the result.  If they had used a 99 out of a 100 test, they would have failed.  And with so many trials out there, being close to the edge on a 19 out of 20 test may not be good enough.

A

[veritas]

As we debate the relative positives vs negatives concerning this vaccine, the bottom line is that the data must be studied further. I believe we're all in agreement that this particular vaccine will go no further, however ,if there are benefits to be derived from this study and can be used in other applications thats good. The debate gets tedious when a point is reached whereby more data or information  is needed to come to some type of educated conclusion. Speaking for myself, I find that new data on any research topic is stimulating because if I felt myself getting bored on any topic then I simply wouldn't read it. Why that is such a difficult concept escapes me. Sometimes the information presented is difficult to understand which certainly adds to the frustration, however, some don't wish to really understand what is being said and doing the necessary research is too daunting. Most want a quick  answer, sought of like wanting a baby without going through labor pains. Funny how that usually never works.

Oh, well, enough for now  ------- we wait for Paris!

v

[Tempeboy]

Seems like a complex issue that evokes strong reactions - understandably.

And although that it is not the miracle we have been hoping for for decades - it does seem to be an important step forward.

Who knows, with PrEP medication and microbicides, this type of vaccination might make part of a range of strategies implemented together that could reduce transmission - like between discordant couples - and I spose that's a good thing.

As well as preventative vaccines there is also research toward vaccines that might work against HIV in People living with HIV - so this research will possibly help us all.

Link to UK site on HIV Vaccination - http://www.aidsmap.com/cms1065624.aspx

[veritas]

Tempeboy,

Nice post. I especially like your link which explains the different avenues being considered for vaccination design.

v

[Tempeboy]

Cheers V,

That info puts it terms that even I can sort of understand.

It helped me understand the difference between a 'preventative' vaccine and a 'therapeutic' vaccine - like the one being discussed in the research section

 http://forums.poz.com/index.php?topic=27011.msg358568;topicseen#msg358568

Take care

J

[Inchlingblue]

The strange thing about this vaccine is that it's not even known how it worked, which is why the whole thing is questionable.  

HOW DOES THE VACCINE WORK?

Researchers are not sure. AIDS experts have long agreed that any HIV vaccine would have to activate both arms of the immune system -- the antibodies that home in on invaders such as viruses to neutralize them, and the T-cells that recognize and destroy viruses.

This vaccine did not appear to generate either response, and yet prevented infection 30 percent of the time.

Even more confusing, among the 51 people who were vaccinated but were infected anyway, the virus replicated just as well as it did among unvaccinated HIV patients. Researchers would not have expected that -- they would have expected the vaccine to at least make the infection less serious, as influenza vaccines do, for example.

"Additional studies are clearly needed to understand how this vaccine regimen reduced the risk of HIV infection," said Dr. Jerome Kim of the Walter Reed Army Institute of Research in Maryland, who helped lead the study.

LINK:

http://www.reuters.com/article/scienceNews/idUSTRE58N5G020090924

[rolf2009]

What a wonderful news....

Really?? After all this is Thailand!

So, you take 16.000,- people (first thing I am missing is in the reports, what age they are, what class they are from, what is their income, etc...) and tell them they get a vaccine (I even don't know, if vaccine is the right word, if you put two meds, which worked rather bad in single tests, together) against HIV (only half, because the other half got placebos) and let them run around and have unprotected sex (protected sex wouldn't make sense, as you want to know if the vaccine works) with everyone in their way. Now, after a timebeing you check them for HIV and found that there is less infection in one group. With less infection, I thought it was about 25%, but I am not hundred % sure. Anyway, that would mean, when I give 50 people over a time of three years a Cola a day and 50 people a glass of water and in the end from the 50 drinking Coke are less infected with HIV, that Coke is a vaccine... No, I don't think so...

There are no reports of how much sex each of these testpersons had and with which kind of people (risk groups, like redlight district, etc...)

For example, if from these two groups of 8.000 in one are around 70%, which frequently visit sexworkers and in the other group the majority of people are faithful partners...how can you ever come to a 'real' conclusion?

Every single testperson must have had the same amount of sex and with basically the same people to get a real result. I also understand that is not possible, but anyway the data they released dosn't show proper statistics for me to jump up and open a bottle.

There is a reason, that Americans conduct their tests in a country like Thailand, which still is a third world country despite them claiming they are not. Not that I condem Thailand, as it is very ambitious with their Red Cross HIV Resaerch Project, but still, things going here to the press might not be everytime entirely true.

Also, I have strongly to agree with bman. As he steted, if there is a vaccine, there will be no need for a cure for all the effected ones (including me), as there is no need. And the line from Mystery "...but death kinda has a natural way of curing things." might be our faith.

Also the mentioning from freewillie99, that his optimism is based on the ever increasing rate of technology and advances in areas not even in existence 10 years ago (plotting the genome, gene manipulation, gene silencing, medications with little to no side effects, identification of the reservoirs where HIV hides and advances towards eradication of these, etc) is completely right, but all the technology and money (imagine the money saved, if there is no real need for a cure, because the uninfected - what a strange word to use - and future generations are protected through a vaccine already) will go in other research and not HIV. And we all know that there are other illnesses in the line to be 'cured'.

And it would be convenient too. Besides the saving of millions of $ - and I mean millions!!! - it is a chance to reduce our world population a little without implementing drastic measures. And we all know, we are too much here on this small planet, don't we...??

So, just go on with your lifes, enjoy it as much as possible and when the times come, it comes... Better having a short life lived in a satisfactory and exhausting lifestyle, than sitting at home, hoping nothing happens to one and wait for the 'cure'...

[J220]

As I thought...the "success" of the Thailand study is now looking like anything but. What a croc....

From the news section here: http://aidsmeds.com/articles/hiv_thai_vaccine_1667_17361.shtml

Second Analysis of Vaccine Trial Casts Doubts on Result

An unrevealed second analysis of the results from the initially lauded RV 144 HIV vaccine trial failed to show a statistical benefit over placebo, according to a ScienceInsider blog entry authored by longtime AIDS journalist Jon Cohen.

Lead scientists from the RV 144 trial conducted in Thailand announced last week that there was a modest reduction in the HIV infection rate among those who received the vaccine. The results were heralded as a triumph by the general media, but were greeted with measured caution by some vaccine experts.

The skeptical experts pointed to the extremely narrow margin of efficacy. While the vaccine reduced the risk of HIV infection by 30 percent, only a handful of volunteers in the massive 16,000-patient study—51 patients in the vaccine group compared with 74 patients in the placebo group—actually became infected during the study, lending to a difference that was just barely statistically significant.

There were also concerns about the fact that the vaccine failed to suppress viral loads in those who did become infected, with experts arguing that a vaccine capable of sparking the immune system to prevent HIV infection would help control HIV replication if infection did occur.

However, some expressed hope that while the vaccine itself would never be approved with such a low rate of success, it might point the way to other more successful preventive vaccines.

Now Cohen reports that a second analysis showed a trend toward benefit in those who were vaccinated, but failed to demonstrate a statistically significant difference. This means the difference was small enough that it could have occurred by chance.

The initial report was based on an intent-to-treat analysis that included all trial participants, including people who may not have received all of the vaccinations or who may have dropped out early. The unrevealed second analysis was per protocol, and only included people who received all their vaccinations on schedule.

According to Cohen, the per-protocol analysis failed to demonstrate a statistically significant difference between the two groups of patients studied. The vaccine efficacy also dropped slightly—a confusing finding, given that a tested vaccine often performs better in per-protocol analyses, given that it eliminates people who weren't properly vaccinated and might not have developed an appropriate immune response to the virus.

This new analysis, said the researchers interviewed by Cohen, casts some doubt on the possibility that the vaccine approach employed in the RV 144 study will have any positive influence on HIV vaccine development.

[newt]

aha ... pass me the deckchair

Protection could have occured by chance (or not), and even if it did not, they don't know why the vaccine worked, and don't know why the peope it didn't work for got HIV (or were they the ones not following the correct protocol?)... hmmm

I await further presentation of the data befor I fold my deckchair up (as ever)

- matt

[xman]

those involved in this trial don't want to accept that it was more a failure than a success and believe me or not this is good news because once the scientific community understands that a preventive vaccine is out of reach they need to speed up for a therapeutic one if they want at least partially stop the disease. this is also necessary due to the astronomic costs of treatment which are unsustainable in the long term. i strongly hope that hiv will be like herpes in the near future or simply a harmless virus in our bodies. we need to tell our immune system how to manage the virus without therapy. once this is archieved eradication shouldn't be necessary.

[xman]

Sadly its obvious (at least for me) that we all are going to be forgotten, they are just going to wait for us to die, it kinda depresses me when i read the success of this vaccine, the more success they have, more doomed we are. Why spending rivers of money on researches for a small percentage of people living with HIV, if they know that the disease ends with them.

Is it only me, who sees things this way?

i disagree. there are more companies investing in therapeutic approaches since this is the more feasable way to combat the disease.

[NYCguy]

sorry to hijack this lovely discussion of whether or not we will be forgotten if and/or when a preventative vaccine is developed, however pertinent that may be, but does anyone know which proteins this one targeted other than gp120?  I'm wondering because Geovax made all their "we will definitely work because we are similar to this one but better" noises and now that the Thai vaccine is turning out to be pretty much nothing on second analysis, I am wondering how that might relate to Geovax, which is in some ways similar but targets gag, pol and env, if I am not mistaken.  Of course they have not commented on the follow-up analysis.

My knowledge of how these things work is so low-tech that I might be completely missing the boat and I suspect Geovax was just trying to jump on the hype band wagon, and in fact it may be that they are completely different.    would love some insight on this from those with more technical knowledge than me.

[newt]

The test is two vaccines together

ALVAC-HIV vCP1521 is a canarypox vector vaccine genetically engineered to express subtype E HIV-1 gp120 linked to a transmembrane anchoring portion of gp41 + gag and protease

AIDSVAX is recombinant gp120 agent

- matt

[NYCguy]

thanks Matt.
Geovax is supposed to express Gag, pol and env delivered in an MVA (as opposed to canary or other fowlpox virus) along with a DNA primer.  To my lay understanding, it sounds different enough that I won't worry too much about similarity to the Thai vaccine. But I really think it's time to give up on gp120... I believe Aidsvax was also used in the Vaxgen trial I participated in in the 90s.  And we all know how that came out.

[veritas]

Actually, gp 120 is a very attractive target because it is expressed on all hiv strains and is constant. I believe the difficulty is in mounting a strong enough immune response to get at that target. See:

http://depts.washington.edu/hptu/gp120.html

I believe gp41 is constant also.

v

[John2038]

Study results (NEJM):

Vaccination with ALVAC and AIDSVAX to Prevent HIV-1 Infection in Thailand