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AIDS vaccine trial set to start

The US government is poised to start a new AIDS vaccine trial, prompting some to caution that it is too soon to initiate such studies after a linkurl:Merck vaccine;http://www.the-scientist.com/blog/display/53633/ not only failed to show effectiveness but also may have increased participants' HIV infection rate. Late last week, the NIH's linkurl:AIDS Vaccine Research Subcommittee;http://www3.niaid.nih.gov/research/topics/HIV/vaccines/advisory/avrs/ voted 23-3 in favor of beginning the PAVE 100 H

By | June 3, 2008

The US government is poised to start a new AIDS vaccine trial, prompting some to caution that it is too soon to initiate such studies after a linkurl:Merck vaccine;http://www.the-scientist.com/blog/display/53633/ not only failed to show effectiveness but also may have increased participants' HIV infection rate. Late last week, the NIH's linkurl:AIDS Vaccine Research Subcommittee;http://www3.niaid.nih.gov/research/topics/HIV/vaccines/advisory/avrs/ voted 23-3 in favor of beginning the PAVE 100 HIV vaccine trial. The study would be conducted by the linkurl:Partnership for AIDS Vaccine Evaluation;http://www.hivpave.org/ (PAVE), which is a consortium of government agencies and government-funded organizations involved in HIV vaccine research, and is sponsored by NIAID. linkurl:Dennis Burton,;http://www.scripps.edu/ims/burton/person.htm a Scripps Research Institute immunologist and member of the advisory panel, urged caution. "We're redesigning the aims of human HIV vaccine research without redesigning the vaccine," Burton, referring to a linkurl:refocusing;http://www.the-scientist.com/blog/display/54488/ of AIDS vaccine research decided upon at an NIH meeting in March, told __Bloomberg News__. "Let's not go into a human experiment without a clear idea of what we're going to learn." Yesterday (Jun 2), linkurl:Anthony Fauci,;http://www.the-scientist.com/article/display/13734/ director of the National Institute of Allergy and Infectious Diseases (NIAID) director told linkurl:__Bloomberg News__;http://www.bloomberg.com/apps/news?pid=20601103&sid=aJ1PwyX5Ng4E&refer=us that he would review the panel's comments and decide "reasonably soon" whether to proceed with the study. The panel's advice is not the only source from which Fauci will draw in making his decision. Fauci will also consider "the thoughts/recommendations of the various PAVE partners, HIV community groups, other NIAID scientific advisory bodies, such as the Clinical Trials Strategic Working Group," according to an Email sent to __The Scientist__ by an NIAID spokesperson. The new vaccine - like the failed Merck vaccine - uses a recombinant vaccine based on adenovirus type 5 (Ad5), but administers a single injection after a "prime-boost" of three DNA-based immunizations designed to stimulate the immune system. The failed Merck Ad5 vaccine was administered in three sequential injections, with no prior DNA-based priming. "The [vaccine] regimen is sufficiently different from the Merck product to warrant further testing," linkurl:Eric Hunter,;http://www.vaccines.emory.edu/scientists/hunter.shtml Emory University vaccinologist and subcommittee chair, said at the panel's linkurl:meeting.;http://www.macrovolt.com/live/dgi_053008/default.aspx According to the NIAID, the vaccine will be tested in the US on 2,400 men who have sex with other men, but trial participants must not have detectable Ad5 antibodies and must be circumcised - the two main differences in enrollment criteria from the failed Merck trial.
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Comments

Avatar of: Ellen Hunt

Ellen Hunt

Posts: 199

June 3, 2008

I am not sanguine about HIV ever having a vaccine, but I support Fauci's decision and think it is the best course for now. I think this trial will show us something very similar to the African trial - at best no detectable effect. \n\nAnalyzing these trials is difficult because, let us say that the HIV rate for those in the trial is half of control population. Is that because of the vaccine or behavior? If it is slightly higher, is it because of the vaccine or behavior change for a vaccine that has mild positive effect on a per-contact basis? Can we trust self-reporting by subjects? I'm not sure we can overall.\n\nMy expectation is that this vaccine, like the previous, will have no meaningful effect. That will teach us something. But no meaningful effect is not harm. HIV is hard to acquire, even MSM high risk subjects have an average of 200 contacts to get infected. So even if the vaccine raises susceptibility to HIV slightly, to class that as harm in the Hippocratic sense is a stretch. \n\nBut perhaps this vaccine may work. I think that is quite unlikely, but if it does the benefit is very large. Weighing no harm against potentially great benefit, I completely support Fauci's decision.
Avatar of: john toeppen

john toeppen

Posts: 52

June 3, 2008

Scientific theories only become theories after a hypothesis is tested by experiment. The words ?trial and error? should be replaced by ?trial and learning experience.? The greatest error is to have no trials and no learning experiences. While this is true for general science, when lives are at risk such a general rule needs to be carefully considered.\n\nOne should not make life and death choices for others as a general rule. The notion of informed consent is critical in matters of this kind, not just for this vaccine, but in all human clinical trials. I would expect that there would be some HIV positive people that would like to try anything that offered hope or contributed to an eventual cure. While the notion of doing no harm is an important consideration, many people will die due to the ongoing spreading of this disease. Failure to act is also a very real risk. We should allow volunteers to make informed choices. \n
Avatar of: Jesse Creel

Jesse Creel

Posts: 4

June 5, 2008

Greetings All,\nI agree with Dennis Burton of Scripps below about the need to consider \ncarefully if PAVE human trails should proceed.\n\nOne PAVE aspect that bears careful consideration is the new version of Ad5 \nis supposed to get around the preexisting immunity that was a problem in the \nMrk Ad5 STEP trials. This may well be the case for the most part. However \nthere will still be anti-Ad5 vector immune responses which could limit \nvaccine efficacy, as a normal course of immune response events following \nadministration of the Ad5 boost.\n\nSecondly, this ant-Ad5 Vector immune response will squander many important \nimmune system components, cellular and soluble, that would be better applied \nto the chosen vaccine antigens/epitopes. This becomes particularly salient \nwhen you consider the need to vaccinate several billion individuals \nworldwide, many of who have immune systems which are immunosuppressed ... \nlimited immunologic potentials... as per the case of the HIV+ and/or \nmalnourished individuals.\n\nRegarding the DNA primes, there is still no convincing evidence of DNA \nVaccine efficacy in humans. I have sent material on this several times to \nthe AIDS Vaccine Research Subcommittee and others in the HIV vaccine \ndevelopment community. I think it unlikely that DNA vaccine will safely show \nefficacy for the forseeable future if at all.\n\n\nIn conclusion, the use of multiple boosters becomes extremely logistically \nproblematic when you consider the need to vaccinate several billion mobile \npeople around the globe more than once.\n\nThanking you in advance for considering these out of the traditional vaccine \ndevelopment box comments.\n\n\nJesse Creel\n\nVaccine Research Advocate\n\n1194 River Valley Dr #3\n\nFlint, MI 48532\n\nEmail: JesseCreel@comcast.net\n
Avatar of: Martin Delaney

Martin Delaney

Posts: 1

June 5, 2008

Bob, I don't understand where you came up with the vote of 23-3 in support of the PAVE trial by the AVRS. I was there. If you add up all the members listed of the committee, including the chair and ex-officios, you get 19 people. Three critics were added for the day to appear more balanced (John Moore, Dennis Burton, Dave Wilkins). Now we've got 22 people. So where does 23-3 come from? And if Moore, Burton and Wilkins were the "only" three voting against the trial, how were they counting Bruce Walker's vote? Anyone who heard him would have a very hard time claiming he was in support of the PAVE 100A. Let's remember that there was a 3rd option in play, that of a much smaller trial of about 750. Several people were in support of the smaller trial rather than the 2500 person juggernaut. The rationale for the larger study over the smaller one kept changing throughout the day. \n\nMuch of the enthusiasm for going ahead was based on a new finding that suddenly appeared in the comparative presentation of the VRC and Merck vaccines. Some people thought they heard new evidence that the Merck vaccine had shown an effect on viral load. Others who heard the same presentation, myself included, heard no such thing. The whole presentation of new data went by so fast, and was so dense, that I doubt more than a few people really understood what they were hearing, let alone it's significance. We long ago learned to exercise extreme caution over such preliminary and post hoc analyses. Instead, here people were jumping on it like it was the equivalent of the Dead Sea Scrolls. The acceptance of the new data was way out of proportion to the true value it should be given. \n\nAnd lets not forget that a great majority of those voting were slated to be participating in the trial. In other words, at least some of their funding was going to come from the study. Was there a single person thus connected to the study who voted against it? Surprise. \n\nAs my own testimony that date stated, from my point of view, there is so much wrong with this trial that as it stands now, I'd have a hard time not campaigning against it in the community.
Avatar of: Jesse Creel

Jesse Creel

Posts: 4

June 6, 2008

Greetings All,\n\nI agree with Dennis Burton of Scripps Research Institute below in (AIDS\nvaccine trial set to start ) about the need to consider carefully if PAVE\nhuman trails should proceed.\n\n"We're redesigning the aims of human HIV vaccine research without\nredesigning the vaccine,"\n\n"Let's not go into a human experiment without a clear idea of what we're\ngoing to learn."\n\nOne PAVE aspect that bears careful consideration is the new version of Ad5\nis supposed to get around the preexisting immunity that was a problem in the\nMrk Ad5 STEP trials by screening of trial participants for preexisting\nadenoviral immunity. Adenoviral immunity can't be avoided if PAVE is shown\nto have the desired trial outcomes and deemed worthy of use in general\nunscreened populations. Regardless, there will still be anti-Ad5 vector\nimmune\nresponses which could limit vaccine efficacy, as a normal course of the\nimmune\nresponse events following administration of the Ad5 boost.\n\nSecondly, this ant-Ad5 Vector immune response will squander many important\nimmune system components, cellular and soluble, that would be better applied\nto the chosen vaccine antigens/epitopes. This becomes particularly salient\nwhen you consider the need to vaccinate several billion individuals\nworldwide, many of whom have immune systems which are immunosuppressed ...\nlimited immunologic potentials... as per the case of the HIV+ and/or\nmalnourished individuals.\n\nThe use of multiple boosters becomes extremely logistically\nproblematic when you consider the need to vaccinate several billion mobile\npeople around the globe more than once.\n\nThe circumcision requirement flies in the face of the real world situation\nas\nexist in many cultures, circumcision is taboo.\n\nRegarding the 3 DNA primes of the PAVE trial, there is still no convincing\nevidence of DNA Vaccine efficacy in humans. I have sent material on this\nseveral times to\nthe AIDS Vaccine Research Subcommittee and others in the HIV vaccine\ndevelopment community. I think it unlikely that a DNA vaccine will safely\nshow efficacy for the foreseeable future, if at all.\n\nAnother disappointing HIV Vaccine trial result may make it very difficult to\nenroll volunteers for future trials.\n\nPlease, let us proceed with extreme caution from here and see if we can't\ncome up with new and innovative approaches.\n\nThanking you in advance for considering these out of the traditional vaccine\ndevelopment box comments.\n\n\nJesse Creel\n\nVaccine Research Advocate\n1194 River Valley Dr #3\nFlint, MI 48532\n\nEmail: JesseCreel@comcast.net\n
Avatar of: anonymous poster

anonymous poster

Posts: 1

June 10, 2008

Dear All\n\nI strongly suggest the trail should commence with HIV positive as the whole world is waiting for breaking news on the cure of HIV/AIDS.\n\nThe only way to improve is by trail and error and there are so many HIV positive ready to be used. If it fails, which I doubt, it will review some issues about the virus that will be used for further research and improvement.\n\n\n

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