AVAC's excellent statement regarding the Phambili trial announcements is now online.
What is quite stunning about the way events have unfolded this week is the lack of information, and the complete failure of just about all of the large, well-funded HIV vaccine research entities to provide any guidance about what has happened. Here are some examples:
The HIV Vaccine Trials Network, who ran both the STEP and Phambili trials, has a link to the Washington Post article "Warning Sent to AIDS Vaccine Volunteers" on their front page. As far as I can see, there is no other information regarding what has happened on the site; the last press release is dated February 7, 2007, the last story in their "In the News" section is dated September 28, 2007.
The Global HIV/AIDS Vaccine Enterprise has a large article about the appointment of their new director on their front page, dated October 11, 2007. Their "latest news" section has a press release about the STEP study from back on September 21, 2007.
The Center for HIV/AIDS Vaccine Immunology also makes no mention of this week's events. The last article in their "In the News" section is also about the appointment of the new director for the Global HIV/AIDS Vaccine Enterprise.
The International AIDS Vaccine Initiative, even though it is the only organization that is independent and not directly linked to NIAID, HVTN, the Global HIV/AIDS Vaccine Enterprise or CHAVI, at least has a link to the NIAID Phambili statement on its front page.
Which brings us to NIAID itself. It is clear that NIAID's response to the media stories is the same response that I obtained on Wednesday from Kathy Stover at NIAID:
"The data and safety monitoring board (DSMB) for the Phambili /HVTN 503 HIV vaccine study examined the available findings from the STEP/HVTN 502 study, which involved the same investigational HIV vaccine. That data showed 24 cases of HIV infection among those volunteers who received at least one dose of the investigational vaccine compared to 21 cases of HIV infection among those who received the placebo. In those volunteers who received at least two vaccinations, there were 19 cases of HIV infection among those who received at least two doses of the investigational vaccine versus 11 cases of HIV infection among those who received two doses of the placebo.
Based on this information, the Phambili DSMB felt it necessary to inform study volunteers of the possibility that the vaccine potentially could increase susceptibility to acquiring HIV infection and to counsel them accordingly on avoiding exposure to HIV. NIAID noted this in its statement and accompanying Q&A document in the spirit of transparency and sharing information with the study volunteers and the research community as it becomes available.
Although the STEP data continues to be analyzed, available findings will be presented at the HIV Vaccine Trials Network meeting in Seattle on November 7. The study volunteers are being informed of the developments and encouraged to return to their study sites for counseling and follow-up."
Like the original NIAID statement and Q&A that were released this past Tuesday, no information is provided as to why the Phambilii DSMB responded differently to what is - supposedly - the same data as reviewed by the STEP DSMB.
So we are left guessing. Did the Phambili DSMB simply insist that they saw evidence of enhancement where the STEP DSMB didn't? This is the implication of the phrase "felt it necessary." If it's just a case of differing interpretations of the same data, is their some rule that precludes anyone from clearly stating that is what has happened here? Sarah Alexander, the Associate Director of Communications at the HVTN, is quoted extensively in yesterday's Washington Blade article, and the way the quotes are presented makes it sound like data from the Phambili trial has also been reviewed. But it's possible that this is just a misunderstanding on the part of the writer, as Alexander makes no direct reference to Phambili data herself (UPDATE II: in an email on 10/27, Sarah Alexander confirmed that both DSMBs reviewed the same data).
It still seems possible at this point that everything that has occurred is related to an understandable desire on the part of the Phambili DSMB to act with an excess of caution. If this is the case, however, it is bizarre that no one is willing to say as much.
UPDATE: Representatives from Merck have confirmed that additional data from the Phambili trial was not involved in the DSMB's decision to caution vaccine recipients about the possibility of enhanced susceptibility to HIV infection. Because distressing evidence of enhancement emerged from a microbicide efficacy trial in South Africa earlier this year, it is not surprising that the Phambili DSMB decided to take an ultra-cautious approach to the issue. What is surprising and very disappointing is that the basis for the DSMB's recommendations could not be articulated more clearly by the trial sponsors.
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