Interesting Read About The Thai HIV Vaccine Study
The positive results of the Thai HIV vaccine study announced today are surprising to many, since it was widely predicted that the study would fail to show a protective effect.
About the study
The vaccine regimen was designed to stimulate both the cellular and the antibody-producing arms of the immune system (for further informationa about vaccines and how they work, see our guide to HIV vaccines).
First, participants would receive ALVAC, a vaccine that used a canarypox vector to deliver selected recombinant HIV sequences in order to stimulate the cellular arm of the immune system to produce HIV-specific cytotoxic T-lymphocytes (CD8+ cells).
Participants received four doses of ALVAC over six months, and vaccinations at months 3 and 6 with AIDSVAX B/E, a vaccine designed to produce an antibody response against the gp120 protein on HIVтАЩs surface, using sequences from two HIV subtypes present in Thailand, B and E.
All participants received counselling on how to protect themselves against infection at the beginning of the study and every six months, as well as being tested for HIV every six months. Anyone who seroconverted during the study received free care and treatment for HIV infection.
The study recruited 16,402 volunteers aged 18-30 in Thailand. All participants were followed for at least three and a half years.
An unpopular study
The RV-144 trial was the biggest HIV vaccine study conducted to date, dwarfing all the other efficacy studies that have taken place, and one that many advocates and scientists said should never have gone ahead.
Back in 2004, as the first participants began to receive vaccinations in Thailand, a group of some of the biggest names in US vaccine research published a letter in Science magazine in which they called for the study to be abandoned.
In particular, researchers were concerned that the products being tested in the vaccination regimen, ALVAC and AIDSVAX, had little chance of producing robust immune responses that would protect against HIV infection, based on the results of previous studies.
They expressed concern over the use of AIDSVAX, after phase III trials in the United States and Thailand reporting in 2003 had shown the vaccine to be тАЬcompletely incapable of preventing or ameliorating HIV-1 infection.тАЭ
The trial was going ahead, at a cost of over $119 million over six years, they said, without a clear scientific rationale. They feared that failure of the study would erode the confidence of public and politicians in HIV vaccine research. Plans for a similar study in the US had been cancelled following the results of the AIDSVAX studies.
Instead, they argued, money should be invested in vaccine prospects that showed evidence of strong immunologic responses in phase I and II studies. (For further information on the debate over the Thai trial, see Types of HIV vaccines).
The RV 144 study continued, despite the controversy, but with little expectation in the wider HIV vaccine field that it would yield a positive result showing a protective effect.
Instead, there was growing optimism that a new vaccine candidate that elicited promising immune responses, developed by Merck, would prove successful in proof of concept studies taking place in the US, Latin America and South Africa.
It was thus a huge shock to the field, when almost exactly two years ago, the investigators in the major study of the Merck vaccine decided to halt the STEP trial following evidence that the vaccine was not effective.
Worse was to follow, as subsequent analysis showed that a subset of participants who received the vaccine were at higher risk of infection. The mechanisms that placed these individuals at higher risk are still not understood.
So, todayтАЩs announcement that the `Thai trial` resulted in a reduced risk of infection for those who got the vaccine is one of the bigger surprises in a field that is becoming accustomed to results that upset the conventional wisdom.
However the design of the Thai trial still leaves a major question unanswered. What part of the vaccine regimen induced protection? Was it ALVAC, which had never been tested in an efficacy trial in HIV-negative individuals? Was it AIDSVAX, despite its failure to protect in two large trials in the US and Thailand? Or was it the combination of the two, despite no clear scientific rationale for why the two vaccines together would be expected to produce a greater protective effect than ALVAC alone?
Some of these questions may be answered when further results from the study are presented at the 2009 AIDS Vaccine Conference next month in Paris, but others will require further clinical studies before the mechanisms that led to a modest level of protection in the Thai study are fully understood.
Re: Interesting Read About The Thai HIV Vaccine Study
sanook,
you obviously know far more about this than I do, which is not saying a great deal I am afraid so I am sorry if the questions are a bit basic, but maybe you could shed some light on the following:
seroconverted - does this mean those who caught HIV? If so, was their treatment the standard Thai government "package", which is hardly confidence inspiring?
subsequent analysis showed that a subset of participants who received the vaccine were at higher risk of infection - in the STEP trial or the Thai trial? If the Thai trial, would that not make the results even better? In either case, how could this happen if the participants receiving the drug and those receiving the placebo were selected at random - surely this must call into doubt any of these tests, unless it was purely "co-incidence"?
Re: Interesting Read About The Thai HIV Vaccine Study
Quote:
Originally Posted by Gone Fishing
sanook,
you obviously know far more about this than I do, which is not saying a great deal I am afraid so I am sorry if the questions are a bit basic, but maybe you could shed some light on the following:
seroconverted - does this mean those who caught HIV? If so, was their treatment the standard Thai government "package", which is hardly confidence inspiring?
subsequent analysis showed that a subset of participants who received the vaccine were at higher risk of infection - in the STEP trial or the Thai trial? If the Thai trial, would that not make the results even better? In either case, how could this happen if the participants receiving the drug and those receiving the placebo were selected at random - surely this must call into doubt any of these tests, unless it was purely "co-incidence"?
Yes, seroconverted does mean someone recentlynewly infected. There are those who have thrown questions on this recent research/findings. I think comments from a recent post on this cover some of the doubts etc. from posters here. You can read more of the professional comments at:
http://www.aidsmap.com/en/news/FC15FEF3 ... D583A2.asp
and:
http://www.aidsmap.com/en/news/464BB0EA ... B82E74.asp
Personally, one can never know or even (as a layman) hope to know enough about this virus, all one can really hope for is that the more trials etc carried out will improve the drugs to combat it.....
:cheers:
Re: Interesting Read About The Thai HIV Vaccine Study
Just to add
'Seroconversion' Definition:
The development of antibodies to a particular antigen (infectious organism); in this case HIV. Seroconversion is a part of the immune response. When people develop antibodies to HIV, they "seroconvert" from antibody-negative to antibody-positive. In other words seroconversion has occurred. It may take from as little as 1 week to several months or more after infection with HIV for antibodies to the virus to develop. After antibodies to HIV appear in the blood, a person will test positive on antibody tests.
:cheers:
Re: Interesting Read About The Thai HIV Vaccine Study
I listened to a Beeb program on this study and the interviewee (expert in field) was positive. She made the following points:
- The study showed a reduced rate of infection by a third.
- Level of success only modest, but after 20 years of failure encouraging.
- Results not good enough to move forwards into production of a vaccine.
- The details results of the study have not yet become available.
- The researchers involved in the study do not know how it works.
- This is the first study in humans of this kind to show a positive result.
- The trial was sufficiently large enough for the results so far to offer encouragement.
- Safe sex counselling may have had an impact on the results.
- HIV strains in Asia differ from those in say Africa so results may not translate.
- The 30% reduction in infection was below the trial target of 50%.
- Research has to continue to discover why the trail had the success that it did.
- They have to establish why the trial was successful, but they do not know what they are looking for.
- Could be the basis of an effective vaccine for the future.
- Genuine protection modest but encouraging results.
